march/april 2010

INTERNATIONAL JOURNAL

PHA RMACEUTICAL
COMPOUNDING
An Af filiated Journal of the
American Phar macists Association

compounding for men

94 Emerging Evidence for Androgen 108 Coenzyme Q 10 Supplementation in the
Replacement Therapy in Aging Men Treatment of Heart Disease
100 Hormonal Influences in Prostate Cancer:
112 Case Report: The Use of Inhaled
An Update of a Complex Issue
Cyclosporine to Treat Bronchiolitis
105 Determining the Causes of Erectile Obliterans Syndrome in a Lung Transplant
Dysfunction Patient

Volume 14 no. 2
Do these patient symptoms sound familiar?

Depression
Anxiety

Stress

Weight gain
Loss of libido
Fatigue
Call 1-888-572-5482 today for world class hormone testing.
Help your patients take the first step to a better feeling tomorrow.
LABORATORY TESTING MADE SIMPLE  ZRT Laboratory
ww.zrtlab.com
 IJPC
March | April | 2010
Volume 14 Number 2

In This Issue...
Features

94 94 Emerging Evidence for Androgen

Replacement Therapy in Aging Men
bethany l. bramwell, bs pharm, rph

100 Hormonal Influences in Prostate Cancer:

An Update of a Complex Subject
Bruce biundo, bs, rph

105 Determining the Causes of Erectile

Dysfunction: Can Medications Be a
Double-Sided Sword?
lavonn a. williams

108 Coenzyme Q10 Supplementation in the

Treatment of Heart Disease
bethany l. bramwell, bs pharm, rph

112 Case Report: The Use of Inhaled Cyclosporine

to Treat Bronchiolitis Obliterans Syndrome
in a Lung Transplant Patient
Linda F. McElhiney, PharmD, RPh, FIACP, FASHP

118 Developing a Tretinoin Oral Liquid for

Patients Who Cannot Take Capsules

100
Linda F. McElhiney, PharmD, RPh, FIACP, FASHP

124 Inventory Information Approval System

Certification and Flexible Spending Account

105
Purchases: A New Year Brings Changes
Brandon Shuey, President & CEO; LaVonn A. Williams

131 Cop’s Best Friend: Preventing the Illegal

Distribution and Transportation of
Prescription Drugs
commander john burke; jeff hill, rph

134 Owning an In-Network Pharmacy and a

Second Out-of-Network Pharmacy that
Performs Compounding: Suggestions on
How to Avoid Being Terminated from
the Pharmacy Benefits Manager Network
Jonathan E. Levitt, Esq.; Todd Mizeski, Esq.

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 89
 IJPC March | April | 2010
Volume 14 Number 2
INTERNATIONAL JOURNAL

Applied PHA RMACEUTICAL

Compounding COMPOUNDING™
Departments
136 Quality-Control:
ADDRESS: 122 N. Bryant, Edmond, OK 73034-6301 USA
92 Prescription TEL: 800-757-4572, 405-330-0094 FAX: 405-330-5622

loyd v. allen, jr., phd, rph From Record Keeping to Key

(ijpc); thomas e. menighan, Performance Indicators: Managing ( Editorial )
bpharm, mba (apha)
Quality in Compounding Pharmacies Editor-in-Chief
Loyd V. Allen, Jr, PhD, RPh
Gláucia Karime Braga, Doctor in
140 Calculations Pharmaceutical Sciences;
Maria José Vieira Fonseca,
Publication Manager
LaVonn Williams
Shelly J. Stockton, BS Pharm,
Doctor in Pharmaceutical Designer
PhD, RPh
Sciences Kari Riley, BFA

142 Basics of Compounding:

Contributing Authors
174 Postscription Gigi Davidson, BSPh, RPh, FSVHP, DICVP
Shelly J. Stockton, BSPharm, PhD, RPh
Considerations for Implementing
176 Index of Advertisers/ United States Pharmacopeia
Chapter <797> Pharmaceutical ( Cir c ulation )
Erratum Compounding—Sterile Preparations,
IJPC Print/Electronic
CompoundingToday.com
Part 18: Verification of Automated RxTriad
Compounding Devices for Parenteral Deb Mehlhaff, BS

Formulations
TEL: (toll free) 800-757-4572 or 405-330-0094
Nutrition Compounding and Finished FAX: 877-757-4575 or 405-330-5622
Preparation Release Checks and Tests EMAIL: dmehlhaff@ijpc.com
loyd v. allen, jr., phd, rph;
150 Acyclovir 5% in Oral Claudia c. okeke, phd, RPh ( I nt eractiv e M edia )
Adhesive Paste Interactive Media Director
Chris Burr, BBA

151 Peer Reviewed

EMAIL: cburr@ijpc.com
Acyclovir 200-mg/5-mL
Oral Suspension ( Adv ertising )
(From the Injection) 160 Chemical Stability of Director of Advertising
Lauren Bernick, BA
Hydromorphone TEL: (direct) 405-513-4236 or (toll free) 800-757-4572 ext. 4

152 Ciclopirox 10% in Hydrochloride in FAX: 877-781-5107

EMAIL: lbernick@ijpc.com
Isopropyl Alcohol Nail Patient-Controlled
Solution Analgesia Injector ( Board of D ir ec tors )
Dristi Khondkar, PhD; Poonam Jake Beckel, PD, Chairman of the Board
Mike Collins, RPh, Treasurer
153 Clotrimazole 1% Oral
Chopra, MS; John P. McArter,
PharmD; Joseph A. Rosen, CPhT; S.
Pat Downing, RPh, Vice President
Bob Scarbrough, BSPharm, RPh, President
Adhesive Paste Kevin Li, PhD
Loyd V. Allen, Jr, PhD, RPh

154 Cyclosporine 10-mg/g 165 Menopausal Women’s ( Editorial Board )

in Oral Adhesive Paste Access Path to Harvey Ahl, RPh
Diane Boomsma, RPh, PharmD, FIACP
Bioidentical Hormone Marianna Foldvari, PhD, RPh
155 Dexpanthenol 5% Gel- Replacement Therapy: Peter R. Ford, BSPharm, FACA, FIACP
Paul F. Grassby, PhD, MRPharmS
Cream An Exploratory Study Hetty A. Lima, RPh, FASHP
Doris Moro, BHA, MRT(MR); Wendy Dave Mason, DPh, fiacp
156 Lamotrigine 25-mg/mL Young, PhD; Richard Stein, John Preckshot, RPh, FIACP
Lawrence A. Trissel, BS, RPh, FASHP
Injection BscPhm, FACA; Winston Isaac, PhD;
Deborah Goodman, PhD David J. Woods, MPharm, MRPharmS, FHPA

157 Metolazone 10-mg/mL 171 Low Dose Naltrexone: ( w ebsit e )

Injection Side Effects and Efficacy
www.ijpc.com
See our Website for subscription services, back issue
orders, products, and a searchable index.
158 Plasticized in Gastrointestinal
Hydrocarbon Gel Disorders
Subscription and Advertising
Jennifer Ploesser; Leonard Information See PAGE 176
159 Oral Adhesive Paste B. Weinstock, MD; Erin Thomas,
PharmD

International Journal of Pharmaceutical Compounding www.ijpc.com

90 Vol. 14 No. 2 | March/April 2010
 Prescription
The Ages of Man
It’s interesting to look at literature and see how the
different stages or ages of man are described. One
descriptive presentation lists the following seven
stages of man as: (1) infant, (2) child, (3) boy, (4)
young man, (5) matrimonial state, (6) parental state,
and (7) old man. This differs from the seven stages
of women in one resource that describes them as: (1)
infant, (2) child, (3) adolescence, (4) young lady, (5)
young lady, (6) young lady, and (7) young lady.
Although there are situations in the earlier stages
of man (infant, child, boy, young man, matrimonial
state) that require medical and pharmaceutical care,
the largest involvement is man as he becomes of age
in the parental state and especially as an old man.
The top 10 health threats that are compiled from
statistics provided by the Centers for Disease Control and Prevention, as
well as other leading organizations, include the following:
1. Heart disease: This is the leading men’s health threat.
2. Cancer: Lung cancer is the leading cause of cancer deaths in men,
followed by prostate and colorectal cancer.
Changing the Game
Remember Psych 101? At the risk of sounding
academic, I have been thinking a lot lately about
the Hierarchy of Needs as defined by Maslow. It’s
not the food and water that have been my con-
cern. Instead, I realize that a substantial number of
pharmacists practice on different places analogous
to one of the five levels—helping them move up the
ladder is part of my job at the American Pharmacists
Association (APhA).
I’m sure you remember Maslow’s pyramid. First
we have to make sure we have the basic necessities
of life—food, air, and water. Once those are assured,
people can worry about things such as safety and
shelter. On up the ladder one goes, through friend-
ship and family, self-esteem and confidence, and
finally morality and creativity, or as we learned, “self actualization” is the
level approached. Smaller and smaller numbers of people—including
pharmacists—reach each of these levels, hence the pyramid.
Why is this on my mind? Well, as an organization, APhA is currently
involved one way or another in more than 50 issues. Some of these are
food-and-water concerns, such as lunch breaks. Others are at the self-
actualization level. Practicing full time as a medication therapy manager
would be at that level (I believe), and APhA is working hard to ensure
that every pharmacist has the opportunity to practice at this level if they
so choose. In between are a host of topics, everything from importation
and Internet pharmacy to behind-the-counter drugs, the U.S. Food and
Drug Administration’s Risk Evaluation and Mitigation Strategy, and
restricted distribution systems.
International Journal of Pharmaceutical Compounding
92 Vol. 14 No. 2 | March/April 2010
3. Injuries: Motor vehicle crashes resulting in fatal accidents
4. Stroke
5. Chronic obstructive pulmonary disease (COPD): Includes bronchitis
and emphysema
6. Diabetes, Type 2 and associated complications: Includes heart dis-
ease, blindness, nerve damage, and kidney damage.
7. Flu: Especially complications, can be deadly
8. Suicide: Depression is an important risk factor.
9. Kidney disease: This can be a complication of diabetes or high blood
pressure.
10. Alzheimer’s disease
This issue of the International Journal of Pharmaceutical Compounding
is focused on “Compounding for Men.” As a man ages, he finds out he
is no longer the indomitable individual he once thought he was. Man is
mortal, subject to injury and disease, and often in need of specific com-
pounded medications for appropriate individualized treatment.
Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
On some of the more basic issues, there is often not a lot that APhA
can do, quite honestly, unless we get between labor and management.
We are not a union representing only the employee pharmacists. In
fact, many managers and owners are also members of APhA. When we
encounter situations that impede pharmacists’ ability to practice at a
professional level and within legal and ethical bounds, then we search
for relevant policies approved by our House of Delegates and start map-
ping out a reasoned response.
Those limitations feed into what has been a natural tendency for
APhA to look more closely at the higher-level issues, such as reposition-
ing the profession for medication therapy management and healthcare
reform—self-actualization. We take hits for operating at that level
sometimes. Some pharmacists complain that they aren’t given time (as
employees) to provide basic counseling, let alone provide medication
therapy management. But I see many practices that have been re-engi-
neered to provide stellar services while meeting dispensing needs. It can
be done, and more pharmacist employers and owners are getting there.
I don’t mind criticism—it makes us better. Hopefully, if we’re off base,
our critics will be constructive and join us in finding solutions. We will
address workplace issues when it might make a difference, but our focus
will continue to be advancement of pharmacists as service providers, not
just dispensers.
If we don’t, who will? And if we don’t, the game will never change.
Thomas E. Menighan, BPharm, MBA
Executive Vice President and CEO
American Pharmacists Association
www.ijpc.com
Your complete source
for compounding chemicals and supplies

• The most comprehensive line of hormones in the industry

• CSOS - Order CII’s online at letcomedical.com and get them tomorrow
• FREE Next Day Air shipping on most chemical orders over $75*
• Expanded selection of chemicals, capsules, and equipment
• Independently tested API’s to ensure highest quality
• Professional technical support services
• ACPE accredited training

*some exceptions apply

2010 NACP Compounding Classes Letco Medical is a leading supplier of fine pharmaceutical ingredients,
pharmacy equipment and specialty pharmaceuticals. We provide
Comprehensive Compounding
chemicals, supplies, and knowledge to compound an extensive range
January 23-24
May 22-23 of dosage forms and delivery systems including inhalation, oral solids,
July 31-Aug 1 controlled release, injectables, topicals, transdermals and liquids.
November 6-7
Veterinary Compounding Call us toll-free at 800-239-5288 or visit us online at letcomedical.com
March 27-28 for more information or to request a catalog.
Hormone Replacement
September 25-26

Class sizes are limited, so register today! Don’t miss

out on this opportunity to learn about the latest in
compounding! Multiple attendee discounts are
available. Ask about our pharmacy student program.
Free training is available to pharmacy students in
their final year of pharmacy school. For more
information or to register, call us at 800-239-5288
or email us at letcoinfo@letcomedical.com.
 Feature
E mer g in g E vidence for

Androgen Replacement
Therapy in Aging Men

|
Abstract
The age-related changes in organ and system function of an individual in-
crease the risk of developing certain diseases. The data presented in this
article reviews current literature on the specific physiological effects of an-
drogen deficiency in disease states and the risks and benefits of testoster-
one replacement therapy specifically in the areas of urologic, cardiac, and
endocrine health.

Bethany L. Bramwell, BS Pharm, RPh

Walgreens
West Plains, Missouri

The aging man confronts functional and

structural changes in his body that affect his
health and quality of life. One of the more
common changes affecting men, especially ag-
ing men, is androgen deficiency, a problem that
is often undiagnosed and untreated. Androgen,
also called androgenic hormones or testoids, is
the generic term for any natural or synthetic
compound (usually a steroid hormone) that
stimulates or controls the development and
maintenance of male characteristics. This
includes the activity of the accessory male
sex organs. Androgens are also the original
anabolic steroids and the precursor of all es-
trogens, the female sex hormones. The primary
and most well-known androgen is testosterone.
Other androgens include1:

• Androstenediol – The steroid metabolite

that is thought to act as the main regulator
of gonadotropin secretion.
• Androstenedione (Andro) – An androgenic
steroid produced by the testes, adrenal cor-
tex, and ovaries. While Andro is converted
metabolically to testosterone and other
androgens, it is also the parent structure

International Journal of Pharmaceutical Compounding www.ijpc.com

94 Vol. 14 No. 2 | March/April 2010

of estrone. Use of Andro as an athletic or body building supplement
has been banned by the International Olympic Committee as well as
other sporting organizations.
• Androsterone – A chemical by-product created during the break-
down of androgens, or derived from progesterone, that also exerts
minor masculinizing effects, but with one-seventh the intensity
of testosterone. It is found in approximately equal amounts in the
plasma and urine of both males and females.
• Dehydroepiandrosterone (DHEA) – A steroid hormone produced
in the adrenal cortex from cholesterol. It is the primary precursor of
natural estrogens. DHEA is also called dehydroisoandrosterone or
dehydroandrosterone.
• Dihydrotestosterone (DHT) – A metabolite of testosterone, and a
more potent androgen than testosterone in that it binds more strongly
to androgen receptors (AR). It is produced in the adrenal cortex.
The physiological and clinical manifestations of andropause include
changes in androgen metabolism, sexual dysfunction, altered body struc-
ture, and psychological changes.2
Hypogonadism (low testosterone) is a medical term for a defect of
the gonads that results in the underproduction of testosterone,3 which
can lead to reduced physical activity, loss of muscle mass and strength,
increased abdominal adiposity, and increased risk of developing heart
disease, diabetes, and osteoporosis. Symptoms of low testosterone can
include erectile dysfunction, feelings of low energy, fatigue, depression,
and decreased ability to recover after injury or illness.4 Androgen re-
placement has demonstrated significant improvement in health-related
quality of life scores.5 Quality of life is lower in hypogonadal men when
compared to men with normal serum testosterone levels, but improve-
ments are seen within three months of initiation of testosterone replace-
ment therapy (TRT), especially in the areas of emotional and social
functioning, mental health, and vitality.
Urology
There has been a long-standing belief in the medical world that
higher testosterone levels increase the risk of prostate cancer (PCa),
yet there is no evidence that supports the existence of this risk.4,6,7
The testosterone-PCa association grew from the work of Huggins
and coworkers in the early 1940s. These researchers reported sig-
nificant benefits to castration in men with advanced PCa along with
rapid clinical redevelopment or progression of PCa with testosterone
supplementation.7 In 1981, researchers Fowler and Whitmore found that
this deleterious effect of testosterone on PCa did not occur unless the
patients had already been castrated. This observation was apparently
shelved or dismissed until recently. Dr. Abraham Morgentaler, Men’s
Health Boston, Harvard Medical School, suggests multiple factors have
contributed to the persistence of the testosterone-PCa association ideol-
ogy. He cites the dramatic results with castration and continued use of
androgen suppression in the treatment of PCa and faults the medical
community for failing to recognize accumulating evidence inconsistent
with the mainstream dogma.
Coward et al at the University of North Carolina evaluated the PCa
risk of hypogonadal men receiving TRT. Eighty-one men, average
age 56.8 years, were followed for nearly three years after initiation of
TRT.8 Subjects had normal baseline prostate-specific antigen (PSA) and
patients with a history of prostatitis were excluded. Average initial total
www.ijpc.com
Feature
testosterone levels were 241.1 ng/dL; 36 months after treatment the
levels were 379.8 ng/dL. Within 22 to 41 months of therapy, four men
(4.9%) developed PCa. In cancer-free men, PSA levels, drawn annu-
ally, did not change significantly for five years. The men who developed
cancer had an increase in PSA from baseline of 1.8 ng/mL at 18 months
and 3.2 ng/mL at 36 months. Researchers concluded that TRT demon-
strated improvements in lipid profile, sexual function, and overall quality
of life. PSA levels remained stable, and the incidence of PCa was no
greater than that of the general population and could be diagnosed and
treated in TRT patients.
With increasing survival rates in patients diagnosed with PCa, along
with longer life expectancy, there is an increasing interest in the use of
TRT in cancer survivors. In the few case studies available, no clini-
cal progression of cancer has been observed in patients on TRT after
successful treatment of PCa.9 Researchers at the University of Southern
California followed 96 PCa survivors who received TRT for the relief of
hypogonadal symptoms.10 Forty-one of the men had an increase in PSA,
but only seven showed radiographic evidence of disease. Thirty-one
men remained on TRT with no increase in PSA or disease progression
after three years of therapy. The remainder either discontinued TRT
due to elevated PSA (which declined after cessation of TRT) or for rea-
sons other than disease progression. The factors associated with patients
continuing TRT were:
• Radical prostatectomy (RP)
• Initial low PSA level
• Concurrent use of dutasteride
Following an RP, up to 80% of men experience erectile dysfunction.
The effects of testosterone on erectile function are well established,
and data supports the use of testosterone to improve the recovery of
erections following RP.11 In a study at Baylor College of Medicine in
Houston, Texas, TRT was initiated in hypogonadal men following RP
with undetectable PSA levels.12 Fifty-seven men, aged 53 to 83, received
TRT for an average of three years. At 13 months after initiation of TRT,
the mean testosterone levels rose from 255 ng/dL to 459 ng/dL, and
none of the patients had a PSA recurrence. Researchers concluded that
TRT can effectively restore testosterone levels in men following RP.
A review of the literature on the relationship between TRT and
the risk of PCa indicates that the current guidelines for replacement
therapy are overly restrictive and should be re-examined. The evidence
indicates that serum testosterone levels are not associated with increased
PCa risk,13 nor does TRT appear to be associated with a recurrence
of PCa in men cured by surgery or radiation. In fact, low testosterone
levels have been found to be associated with advanced PCa. Researchers
have attempted to develop a satisfactory conceptual model to explain
the inconsistencies in testosterone replacement on prostate growth in
castrated versus noncastrated men. Exogenous androgens do not appear
to significantly increase intraprostatic testosterone levels in hypogo-
nadal men. Prostate growth is apparently very sensitive to fluctuations
in androgen levels at very low concentrations and insensitive to any
fluctuations at high concentrations.14 The prostatic effect of testosterone
is facilitated by binding to the AR, but maximal androgen-AR bind-
ing occurs at testosterone levels far below physiological range. Once
maximal androgen-AR binding is achieved, further testosterone has
little prostatic effect. In situations where serum testosterone levels are
below the maximum androgen-AR, as seen in castration, addition of
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 95
Feature

Rx
Testosterone 25-mg/g Topical
Gel
For 100 g
Testosterone 2.5 g The use of testosterone replacement therapy in men with heart
Ethyl alcohol 95% 70 mL
Carbopol 940 1 g significant benefits.15 A growing body of evidence suggests that androgen
Trolamine qs
Purified water qs 100 g vascular disease (CVD) and testosterone replacement could potentially
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Dissolve the testosterone in the ethyl alcohol and mix well.
4. Disperse the carbopol 940 slowly on the solution from step 3 with
rapid agitation.
5. Add sufficient purified water to 100 g and mix well.
6. Add the trolamine and mix well to obtain the desired viscosity.
7. Package and label.
STABILITY
A beyond-use date of up to 30 days can be used for this preparation.
testosterone can lead to PCa growth. This proposed saturation model
accounts for some of the previous contradictory findings in PCa studies
and indicates that there is a limit to the capacity of testosterone to direct
PCa development.
Cardiology
disease is gaining popularity as new evidence consistently indicates
deficiency plays a role in the development and progression of cardio-
reduce CVD risks in hypogonadal men.16 Recent studies have shown
that androgen deficiency is associated with higher mortality rates pre-
dominantly due to CVD.17
Androgen deficiency is associated with adverse cardiovascular risk
factors including higher levels of total cholesterol and low-density
lipoprotein (LDL), increases in pro-inflammatory cytokines, increases
in arterial wall thickness, and endothelial dysfunction.18 Low serum
testosterone levels have also been found to be independently associated
with a higher incidence of cardiovascular events, regardless of coronary
risk factors and endothelial function.17 But, clear vascular improvements
are seen when deficient testosterone is replaced. Arterial vasoreactivity
is restored; pro-inflammatory factors, total cholesterol, and triglycerides
are reduced; and endothelial function is improved.
Androgen deficiency is common in men with chronic heart failure
(CHF) and is associated with increased rates of morbidity and mortal-
ity.19 CHF is characterized by impaired cardiac function, progressive

Rx
Testosterone 100-mg/g in
Pluronic-Lecithin Organogel
For 100 g
Testosterone 10
Propylene glycol 5
Ethoxy diglycol 5
Lecithin:isopropyl palmitate 23
Pluronic 20% Gel qs 100
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Mix the testosterone with the propylene glycol and the ethoxy
diglycol.
4. Incorporate the lecithin:isopropyl palmitate and mix well.
5. Add the Pluronic 20% gel geometrically, using a shear mixing
method, to final weight and mix well.
6. Package and label.
STABILITY
A beyond-use date of up to 30 days can be used for this preparation.
catabolic metabolism, androgen imbalance, and declining skeletal
muscle bulk and strength. Androgens appear to play a critical role in
the pathophysiolgical changes in the failing heart.20 Animal models
have shown that androgen deficiency significantly aggravates cardiac
sympathetic function in heart failure, characterized by elevated serum
norepinephrine (NE), decreased cardiac NE, and tyrosine hydroxylase
protein. TRT reverses these adverse effects while also demonstrating
g a neuroprotective effect independent of the AR. Androgens appear to
augment angiogenesis, critical to cardiovascular repair and regenera-
g
tion (interestingly, this effect is specific to male endothelial cells), while
g
androgen deficiency dramatically reduces neovascularization.21 In men
g with moderately severe CHF, testosterone replacement has been shown
g to improve exercise capacity, muscle strength, insulin sensitivity, and
baroreflex sensitivity.22
While total serum testosterone is often normal in CHF patients,
free testosterone is low in the majority of patients. Dehydroepiandros-
terone-sulfate (DHEA-S) is often low as well.23 Low free testosterone
and DHEA-S are associated with higher New York Heart Association
(NYHA) class in CHF. Lower free testosterone and DHEA-S and higher
sex hormone-binding globulin (SHBG) are predictors of all-cause mor-
tality risk in men. SHBG levels are key to bioavailable androgens. High
levels of SHBG are also associated with increased mortality and disease
severity in men with CHF.24
Abnormal estradiol levels are also associated with disease severity,
prognosis, and mortality in men with CHF. As estrogens are formed by
the aromatization of testosterone, abnormal estradiol levels would be
expected in CHF patients. Researchers have found an interesting as-
sociation between circulating estradiol levels and survival rates in male
CHF patients. Higher mortality rates are seen in men with both high

International Journal of Pharmaceutical Compounding www.ijpc.com

96 Vol. 14 No. 2 | March/April 2010
 Sterile. Convenient. Economical.
Steri-Dropper 2-packs from EPS ! ® ®

2 bottles
per pack means
less waste!

Tired of losing money, risking

contamination or wasting
sterile bottles because you
only need one or two? EPS
solves the problem with
2 sterile bottles per EPS can also supply you with a variety of
individual pack our Steri-Dropper 2-packs -
non-sterile bottles for unlimited applications.
sterile ophthalmic dropper
bottles of stearate-free* resin, packed 2 per blister.
Choose from 3, 7, 10 or 15 ml sizes with snap-in
dropper tips and polypropylene caps. Another
EPS, INC. ®

Extra Personal Service in supplying pharmacy

innovative idea from the extensive EPS line that packaging needs around the world
includes lotion, spray, solution and tamper-evident Milton Building, 70 Industrial Drive
bottles in a full range of sizes. Contact us for Ivyland, PA 18974
literature and samples. 800-523-8966 Fax: 800-323-8966
215-396-8600 Fax: 215-396-6662
www.medidose.com E-mail: info@medidose.com

*Regular vial resins may contain zinc stearate which reacts with ethylene oxide, a commonly used sterilizing agent. Through a series of chemical processes involving
components of ophthalmic medication, totally unacceptable particles may form. EPS® INC. eliminates this possibility using and sterilizing only stearate-free resins.

PHARMACY SUPPLIES HOTLINE: 1-800-523-8966

Feature
and low estradiol levels when compared to midline levels.18 The high
and low estradiol groups, however, demonstrate vastly different clinical
characteristics. Men with lower serum estradiol levels (<12.9 pg/mL)
have higher serum total testosterone, lower serum DHEA-S, advanced
NYHA class, hepatic impairment, and lower total body fat. In contrast,
men with higher estradiol levels (>37.40 pg/mL) have elevated serum
bilirubin and liver enzymes and low serum sodium. The highest three-
year survivability rate (82.4%) is seen with serum estradiol levels of
21.80 to 30.11 pg/mL.
Similar findings are found in the relationship between circulating
SHBG, testosterone, and disease prevalence in abdominal aortic aneu-
rysms (AAA) in elderly men. Patients with AAA have low serum total
and free testosterone, and high luteinizing hormone levels.25 Research-
ers conclude that hypogonadism may be involved in occlusive vascular
disease and arterial dilation.
Testosterone replacement therapy also appears to exert a cardiopro-
tective effect against myocardial ischemia/reperfusion injury in animal
models.26 Testosterone administration increases post-ischemic recovery
of aortic flow, cardiac output, left ventricular developed pressure, and
contractility during reperfusion.
Endocrinology
Low testosterone levels are associated with abdominal obesity,
metabolic syndrome, and type 2 diabetes.27 There is a significantly lower
risk for later diabetes with higher levels of total testosterone.28 Whereas,
higher estradiol levels are associated with an increased risk of later
diabetes. Patients undergoing androgen deprivation therapy for PCa
have shown deleterious effects on insulin sensitivity and body fat mass.
Several studies have found a beneficial effect of testosterone replace-
ment on glycemic control in type 2 diabetes.29 Testosterone replacement
in hypogonadal men with metabolic syndrome has demonstrated posi-
tive improvements in metabolic control. Low testosterone levels can lead
to elevated fasting insulin, glucose, and HbA1C levels and may predict
the onset of type 2 diabetes.30,31 The resulting visceral adiposity acts an
endocrine organ, promoting endothelial dysfunction and vascular dis-
ease. Androgen replacement improves insulin sensitivity, fasting glucose,
and HbA1C levels.
Decreases in serum testosterone and elevated estradiol are charac-
teristic in diabetic males. Animal models have shown that an elevated
estradiol level persists even after castration, suggesting an alternative
origin for excess estradiol in diabetes.32 Diabetes increases renal and
ocular aromatase activity, but specifically, the diabetic kidney appears
to produce estradiol. This estrogen production mechanism is associated
with a high level of renal injury and may contribute to the progression
of end-organ damage seen in diabetes.
The adverse side-effects of the glitazones (e.g., pioglitazone, rosigli-
tazone), including CHF, osteoporosis, weight gain, and edema have
been frequently reported. Glitazones decrease androgen production,
attenuate AR activation, and increase binding to SHBG. The resulting
reduction in bioavailable testosterone explains the adverse effects of
the glitazones on organ systems.33 Studies are warranted on androgen
replacement in diabetic men on glitazones to establish whether the
adverse effects could be ameliorated or overcome by replacing deficient
androgens.
The evidence for TRT is strong and consistent for symptoms of
hypogonadism and disease, and the concern of some physicians about
an increased risk of PCa with testosterone supplementation is not
International Journal of Pharmaceutical Compounding
98 Vol. 14 No. 2 | March/April 2010
substantiated by decades of research.4,6 There is a significant increase in
all-cause mortality risk for men with low free testosterone levels.34 The
current guidelines recommend evaluating testosterone levels as routine
screening for men starting at 40 to 50 years of age to establish a baseline.
TRT should be discussed with symptomatic patients with total serum
testosterone levels <300 ng/dL. In older men, levels of bioavailable
testosterone, along with or instead of serum levels, should be obtained.
Serum bioavailable testosterone levels of less than 70 ng/dL in symptom-
atic men should warrant an empirical trial of TRT. A three-month trial
of TRT can be considered in symptomatic patients with slightly low or
borderline serum total testosterone levels.35 Therapy should be assessed
and adjusted accordingly every three to six months.
Testosterone supplementation has increased substantially over the
past several years with various delivery modalities utilized. Since the
introduction of commercially manufactured testosterone gels in 2000,
the transdermal dosage form has grown to be the preferred method of
testosterone delivery. Serum levels with gels reach steady state within
24 hours, and their kinetic profile is similar to that of the patch without
the risk of site reaction.36 Gels have demonstrated superior tolerability
while also allowing for dose flexibility. Injectable testosterone esters have
fallen out of favor because of the associated peaks and troughs, as well as
their higher risk of polycythemia.
Conclusion
Hypogonadism among aging men is common but sorely under-
diagnosed and often untreated. Current evidence implicates androgen
deficiency as a significant risk factor for CVD and type 2 diabetes and
ameliorates previous concerns of increased risk of prostate disease with
replacement therapy. Androgen replacement in hypogonadal men is a
viable option to improve functional status, prevent disease development
and progression, and improve quality of life in aging men.
References
1. [No author listed.] Wikipedia. Androgen. [Wikipedia Website.] Available
at: http://en.wikipedia.org/wiki/Androgen. Accessed January 29, 2010.
2. Delev DP, Kostadinova II, Kostadinov ID et al. Physiological and clinical
characteristics of andropause. Folia Med (Plovdiv) 2009; 51(1): 15–22.
3. [No author listed.] Wikipedia. Hypogonadism. [Wikipedia Website.] Avail-
able at: http://en.wikipedia.org/wiki/Hypogonadism. Accessed January
29, 2010.
4. Miner M, Canty DJ, Shabsigh R. Testosterone replacement therapy in
hypogonadal men: Assessing benefits, risks, and best practices. Postgrad
Med 2008; 120(3): 130–153.
5. Taniguchi H, Kawa G, Kinoshita H et al. Androgen replacement therapy
improves health-related quality of life in late onset hypogonadism
patients. Hinyokika Kiyo 2009; 55(12): 741–744.
6. Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone
replacement therapy: A review. Ther Clin Risk Manag 2009; 5(3): 427–448.
7. Morgentaler A. Guilt by association: A historical perspective on Hug-
gins, testosterone therapy, and prostate cancer. J Sex Med 2008; 5(8):
1834–1840.
8. Coward RM, Simhan J, Carson CC 3rd. Prostate-specific antigen
changes and prostate cancer in hypogonadal men treated with testoster-
one replacement therapy. BJU Int 2009; 103(9): 1179–1183.
9. Rhoden EL, Averbeck MA Testosterone therapy and prostate carcinoma.
Curr Urol Rep 2009; 10(6): 453–459.
www.ijpc.com
 Feature

10. Leibowitz RL, Dorff TB, Tucker S et al. Testosterone replacement syndrome and improves glycemic control in men with newly diagnosed
in prostate cancer survivors with hypogonadal symptoms. BJU Int [In type 2 diabetes and subnormal plasma testosterone. J Androl 2009;
print]. 30(6): 726–733.
11. Khera M. Androgens and erectile function: A case for early androgen 31. Traish AM, Saad F, Guay A. The dark side of testosterone deficiency:
use in postprostatectomy hypogonadal men. J Sex Med 2009; 6(Suppl II. Type 2 diabetes and insulin resistance. J Androl 2009; 30(1): 23–32.
3): 234–238. 32. Prabhu A, Xu Q , Manigrasso MB et al. Expression of aromatase, an-
12. Khera M, Grober ED, Najari B et al. Testosterone replacement therapy drogen and estrogen receptors in peripheral target tissues in diabetes.
following radical prostatectomy. J Sex Med 2009; 6(4): 1165–1170. Steroids [In print].
13. Isbarn H, Pinthus JH, Marks LS et al. Testosterone and prostate can- 33. Carruthers M, Trinick TR, Jankowska E et al. Are the adverse effects
cer: Revisiting old paradigms. Eur Urol 2009; 56(1): 48–56. of glitazones linked to induced testosterone deficiency? Cardiovasc
14. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and Diabetol 2008; 7: 30.
prostate cancer: The saturation model and the limits of androgen- 34. Vikan T, Schirmer H, Njølstad I et al. Low testosterone levels and
dependent growth. Eur Urol 2009; 55(2): 310–320. SHBG levels and high estradiol levels are independent predictors of
15. Malkin CJ, Jones TH, Channer KS. Testosterone in chronic heart type 2 diabetes in men. Eur J Endocrinol [In print].
failure. Front Horm Res 2009; 37: 183–196. 35. Hugh Jones T. What should I do with a 60 year old man with a slightly
16. Traish AM, Guay A, Feeley R et al. The dark side of testosterone defi- low serum total testosterone concentration and normal levels of serum
ciency: I. Metabolic syndrome and erectile dysfunction. J Androl 2009; gonadotrophins? Clin Endocrinol (Oxf) [In print].
30(1): 10–22. 36. Lakshman KM, Basaria S. Safety and efficacy of testosterone gel in the
17. Akishita M, Hashimoto M, Ohike Y et al. Low testosterone level as a treatment of male hypogonadism. Clin Interv Aging 2009; 4: 397–412.
predictor of cardiovascular events in Japanese men with coronary risk
factors. Atherosclerosis [In print]. Address correspondence to Bethany L. Bramwell, BS Pharm, RPh, Compound-
18. Traish AM, Saad F, Feeley RJ et al. The dark side of testosterone defi- ing Pharmacist, Walgreens District #306, Walgreens, 1010 Worley Drive, West
ciency: III. Cardiovascular disease. J Androl 2009; 30(5): 477–494. Plains, MO 65775. E-mail: bethany.bramwell@walgreens.com
19. Jankowska EA, Rozentryt P, Ponikowska B et al. Circulating estradiol
and mortality in men with systolic chronic heart failure. JAMA 2009;
301(18): 1892–1901.
20. Han Y, Fu L, Sun W et al. Neuroprotective effects of testosterone upon
cardiac sympathetic function in rats with induced heart failure. Eur J
Pharmacol 2009; 619(1–3): 68–74.
21. Sieveking DP, Lim P, Chow RW et al. A sex-specific role for androgens
in angiogenesis. J Exp Med [In print].
22. Caminiti G, Volterrani M, Iellamo F et al. Effect of long-acting tes-
tosterone treatment on functional exercise capacity, skeletal muscle
performance, insulin resistance, and baroreflex sensitivity in elderly
patients with chronic heart failure a double-blind, placebo-controlled,
randomized study. J Am Coll Cardiol 2009; 54(10): 919–927.
23. Güder G, Frantz S, Bauersachs J et al. Low circulating androgens and
mortality risk in heart failure. Heart [In print].
24. Pascual-Figal DA, Tornel PL, Nicolás F et al. Sex hormone-binding
globulin: A new marker of disease severity and prognosis in men with
chronic heart failure. Rev Esp Cardiol 2009; 62(12): 1381–1387.
25. Yeap BB, Hyde Z, Norman PE et al. Associations of total testoster-
one, sex hormone-binding globulin, calculated free testosterone, and
luteinizing hormone with prevalence of abdominal aortic aneurysm in
older men. J Clin Endocrinol Metab [In print].
26. Borst SE, Quindry JC, Yarrow JF et al. Testosterone administration
induces protection against global myocardial ischemia. Horm Metab Res
[In print].
Potts & Associates is the firm with the
27. Schubert M, Jockenhövel F. Testosterone and the metabolic syndrome. experience to assist you in planning
Urologe A [In print]. your IV Clean Room, Compounding
Laboratory, and presenting a more
28. Vikan T, Schirmer H, Njølstad I et al. Endogenous sex hormones and professional image to your customers.
LEE PHARMACY . FORT SMITH, AR
the prospective association with cardiovascular disease and mortality in Call us today or visit us online.

men: The Tromsø Study. Eur J Endocrinol 2009; 161(3): 435–442.

29. Corona G, Mannucci E, Forti G et al. Following the common as-
sociation between testosterone deficiency and diabetes mellitus, can 5050 BOYD BLVD | ROWLETT, TEXAS 75088 (DALLAS, TX Suburb)

testosterone be regarded as a new therapy for diabetes? Int J Androl main 9 7 2 . 4 7 5 . 4 3 7 1 | 9 7 2 . 4 7 5 . 4 6 2 0 | toll free 8 0 0 . 2 5 5 . 5 4 9 8
fax 9 7 2 . 4 7 5 . 4 8 3 9 | www.robtpotts.com

2009; 32(5): 431–441.

30. Heufelder AE, Saad F, Bunck MC et al. Fifty-two-week treatment with Serving Pharmacists Since 1954
diet and exercise plus transdermal testosterone reverses the metabolic

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 99
 Feature
Hormonal Influences in
Prostate Cancer:
A n U p d a t e o f a Complex Subject

Abstract
Pharmacists who are involved
with patients and physicians
have a tremendous opportunity
to serve in the realm of prostate
cancer, and there are numerous
compounding opportunities. For
example, compounded testos-
terone gels can help keep testos-
terone levels in the mid to upper
range with proper dosing and
patient counseling. Also, estra-
diol levels can be held in check
or lowered by compounding aro-
matase-inhibitors such as anas-
trazole or letrazole into the lower
doses that men require, rather
than their more potent versions
for female patients. Nutraceuti-
cals such as omega-3 fatty acids,
vitamin D, zinc, and selenium all
play an important role in pros-
tate health, as these agents have
5α-reductase inhibiting and anti-
inflammatory properties. More
than anything else, we see that
the pathophysiology of prostate
cancer, although quite complex,
is being explored at an amazing
rate.The author believes that hor-
monal balance is critical, and that
it is largely hormonal imbalance
that is involved in prostate dis-
ease. In that regard, the author
concludes that the levels of tes-
tosterone, estradiol, and dihy-
drotestosterone experienced at a
more youthful age are vital if we
are to improve prostate health.

International Journal of Pharmaceutical Compounding www.ijpc.com

100 Vol. 14 No. 2 | March/April 2010
 Feature

Bruce Biundo, BS, RPh

Professional Compounding Centers of America
Houston, Texas
. ..“Currently, the preponderance
of the evidence does not support
Let us take a deep breath as we enter the concept that normal serum
into this discussion of the hormonal levels of testosterone are
influences in prostate cancer.
a ssociated with increased risk of
prostate malignancy.”
For decades, we have been cautioned about
the primary male hormone, testosterone (T),
and its role in prostate cancer (PCa) and how
caution should be used in monitoring its levels
whose work was published in 1941.3 While • Years of studies about T therapy have not
in aging men. We have been assured that if
that research has had enormous implications shown an association with high cancer
there were only one thing that we were sure
and influences, it was severely limited by rates6
about in PCa, it was that T caused it. There
was this devilish issue, though; if T was the the sample size (two), and by the fact that it
could not foresee that years of T study would One particular study states, “Currently,
primary cause, how would we explain that PCa the preponderance of the evidence does not
occurred primarily in older men? Why did it severely undermine its conclusions. Major
studies include: support the concept that normal serum levels
not cause cancer when the levels were at their of testosterone are associated with increased
highest—in the earlier years of adulthood? • PCa risk is unrelated to serum T4 risk of prostate malignancy.”7 It must be stated,
Could it be that this was a very slow develop- • Low T is not protective against PCa5 however, that not all studies arrive at the same
ing cancer and that it took long exposure for
the disease to express itself ? Perhaps so, but
| Analytical Research Laboratories |
there have been researchers who explored

qual i ty:
deeply the answers to the possible role of the
potent androgen, dihydrotestosterone (DHT).
Considered to be the more potent androgen
in the prostate by most scientists,1,2 DHT has
been the subject of great interest and research
in recent years. Then enters the subject of the highest or finest standard
estrogen. Could estradiol (E2), the most potent
estrogen, have a strong influence in the pros- Resource for Compounding Pharmacists, Quality Control Testing, Excellent Customer Service
tate as it does in other tissue? For years, there
has been speculation about the role of E2 in
regards to the prostate, both in terms of Benign
Prostatic Hypertrophy (BPH), and, more
importantly, PCa. And, how does progesterone
fit into the picture: might it have a protective
role here, and, if so, exactly what is that role?
All of these questions are of interest and all
of them stir up even more questions. Ambi-
tiously, our goals in this article include: (1) to
examine the significant points of many areas of
research in the area of hormonal influences in
PCa, (2) seek to show the inter-relations of T,
E2, and DHT, (3) clarify what we believe to be
significant points, and (4) possibly point to the
protective, rather than the causative, role of T
in PCa.
Potency Determination | Sterility and Endotoxin
Stability Studies | <795> and <797> Consulting
Testosterone
There has been a long-standing fear Complaint Sample Testing | *Online Sample Submission
that the use of T increases the risk of PCa,
influenced strongly by the work of Huggins, | 800-393-1595 | Call or visit ARL today!| www.arlok.com |

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 101
Feature
conclusions. In one review of twenty-five stud-
ies, four of them showed a positive association
between high serum T and risk of PCa, fifteen
showed no association, and six of them showed
a reduced risk with high serum T.8
Hormone Nuclear
Receptors
It is commonly known that T exerts much
of its activity through its attachment to the
androgen receptor (AR). What is less known is
the role of estrogen receptors; more specifi-
cally, the estrogen receptors in the prostate. It
is of great importance to note in any discus-
sion of the role of estrogen at the receptor that
Si m p l y s t a t e d ,
ER α c o n t r i b u t e s
to tumor
proliferation,
w h i l e E Rβ
contributes
to tumor
suppression.
there are two receptors, alpha (ERα) and beta
(ERβ). The discovery of the second recep-
tor, ERβ, was revealed in a 1996 article and
attributed to the work of Jan-Ake Gustafsson,
(formerly from Sweden, now affiliated with
the University of Houston in Texas).9 The im-
portance of this cannot be overstated because
this discovery is of vital importance in prostate
disease. Simply stated, ERα contributes to
tumor proliferation, while ERβ contributes
to tumor suppression.10 Researchers have also
found that mice lacking ERα do not develop
PCa.11 There is another receptor complexity
in the prostate: there is cross-receptor activ-
ity, so that androgens can attach to ERβ and
estrogens can attach to the AR. Specifically,
it has been demonstrated that DHT can bind
to ERβ as well as the AR, and E2 can bind to
both as well.12 In recent years, the role of E2 in
prostate growth and carcinogenesis has been
studied extensively; we now see this role pri-
International Journal of Pharmaceutical Compounding
102 Vol. 14 No. 2 | March/April 2010
D HT, but not Testosterone, seems
t o have a role in carcinogenesis
in the prostate, although that
function is not fully explain ed.
marily as a result of the ERα. In an April 2008
article, Singh et al made several compelling
statements:13
ERβ may be under androgenic
regulation of the prostate as sug-
gested by its down regulation in
castrated rats, which is reversed
by subsequent testosterone
administration. In light of the
age-associated declines in tes-
tosterone levels in humans, this
may be a possible modulating
factor in the regulatory role of
ERβ in aging men and may have
important implications.
This is highly significant, and an important
part of the complex nature of prostate carcino-
genesis, as it suggests that we may have long
been looking at the wrong end of the T spec-
trum. Dr. Abraham Morgentaler of Harvard
Medical School has written extensively about
this phenomenon14 and is strongly influential
in examining the role of T supplementation in
older men, particularly the relationship with
PCa.
Estradiol
While E2 has long been suspected by some
as having a role in prostate disease, including
BPH as well as PCa, the mechanism by which
it affects prostate growth and tumor prolifera-
tion is beginning to emerge as an inflammatory
process.15,16 E2 is involved in the inflammatory
process, through ERα, while T is involved in
anti-inflammatory activity, perhaps through
ERβ.13,17 Ellem et al, in a November 2009 ar-
ticle, concluded that elevated T in the absence
of E2 leads to development of hypertrophy
and hyperplasia, but not malignancy, in the
prostate.17 On the other hand, high E2 and low
T have been shown to lead to the development
of inflammation upon aging and the emer-
gence of premalignant lesions. Further, they
state that it is the activation of ERα that leads
to this inflammation and proliferation. There is
a self-generating cycle involved in the inflam-
matory process: aromatase, the enzyme system
that metabolizes T to E2, may be enhanced by
inflammatory cytokines. E2 itself is capable
of inducing prostatic inflammation, and this
may serve to establish a cycle of increased aro-
matase, local estrogen metabolism, and subse-
quently greater inflammation. More evidence
of the anti-inflammatory role of T is found in
the study by Maggio and colleagues,18 in which
the authors state “…a close relationship exists
between the development of a proinflamma-
tory state and the decline in T levels, two
trends that are often observed in aging men.”
Yatkin et al16 state that age-related increases in
chronic prostatitis, a frequent prestate of PCa,
is associated with decreased T and decreased
T to E2 ratios, and, in normal conditions in an
aging male without elevated E2 and decreased
T, the pro-inflammatory action of E2 would
be blocked by androgen. It would appear that
it is not the action of E2 alone that is involved
here but rather the changing E2 to T ratio that
is significant.
Dihydrotestosterone
In the prostate, DHT is 10-fold more po-
tent than testosterone.13 While T is the major
circulating androgen, it is mainly DHT that is
found in tissues.13 Also, in major male popula-
tion studies involving Oriental-Americans,
Caucasian Americans, and African-Americans,
there were differences in the DHT/T ratios.
Among Oriental-Americans, with lower rates
of PCa, the DHT/T ratios were lower than
those of Caucasian Americans, and even
more so compared with African-Americans,
the group among the three with the highest
rates of PCa.13 It is evident that DHT plays
an important role in carcinogenesis, exerting
a more causative rather than a more protec-
tive role. Since the 5α-reductase enzyme is
responsible for the metabolism of T to DHT,
www.ijpc.com
 Feature

the use of inhibitors of that system have been mediated through a self-perpetuating cycli-
used to treat prostate disease. Both finasteride
and dutasteride have been studied in men for Testosterone cal process with aromatase and inflamma-
tory cytokine involvement. DHT, but not T,
E:CompoundBPH, and toIJPC-2004
ad rev a lesser extent, as a preventive
2/3/10 1:13 PM Page 1
for PCa.19-21 Saw Palmetto (Serenoa repens), h as affinity for seems to have a role in carcinogenesis in the
prostate, although that function is not fully

n ot only the AR
a widely used supplement, is also believed to explained. Through the thoroughly researched
have this same activity, and is the continu- work of Isbam and colleagues,24 we see that

ing subject of study. Usual dose is 160 mg of
standardized extract twice a day.22 Although
it may involve the Paddock
blocking of T IJPC Ad 2010
from those
receptors, metabolites of DHT are also shown
Title:theORA 1/2 Ad
to bind to ERβ, although significance of
that is not clear.23
Convert to 4-color
but also ER β ,
T may have a very useful role in protecting
the prostate against the inflammatory actions
a nd that may be
of E2, and that, at the very least, we should
be conscious of the fact that PCa occurs at a
time when tesosterone levels, but not E2 and
a major key to
DHT, are declining. T has affinity for not only
the AR but also ERβ, and that may be a major

Progesterone
f uture studies.
Need one HI-Res PDF and saved on a CD and One proof. key to future studies. Therapy that helps to
maintain T and DHT levels and control E2
There is some discussion about the prophy- may be desirable and many physicians appear
lactic use of progesterone in men, primarily there is a good premise for the consideration of to be influenced by these concepts.
based on the possibility that it may be an progesterone for prostate health. Pharmacists who are involved with patients
effective 5α-reductase inhibitor. To this point, and physicians have a tremendous opportunity
after extensive searching, we find that there is to serve in the realm of PCa, and there are
scant evidence of this action, although some Conclusion numerous compounding opportunities. For
experimental forms of progesterone have been We find that there is a great deal of new example, compounded T gels can help keep T
shown to have this activity.2 At the very least, evidence involving E2 in PCa, perhaps being levels in the mid to upper range with proper

T O P I C A L S
When swallowing a tablet is a problem...
I N J E C T A B L E S

O R A L L I Q U I D S

A Spoonful from Paddock

O R A L S O L I D S

S U P P O S I T O R I E S

Helps the Medicine Go Down C O M P O U N D I N G

Compounding
Vehicles

Ora-Blend® combines the suspending qualities of Ora-Plus® in a

1:1 ratio with the flavoring of Ora-Sweet®.
 Also available in sugar-free Ora-Blend SF.
 Documented Stability Studies for over 80 formulations using Ora-Plus,
Ora-Sweet, Ora-Sweet SF, Ora-Blend, and Ora-Blend® SF.
Professional
Compounding
Support

800.328.5113 www.paddocklabs.com prof_affairs@paddocklabs.com 0311-10-0110

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 103
Feature
I believe that
hormonal
balance is
critical, and
tha t i t i s l a r g e l y
hormonal
im b a l a n c e t h a t
is involved
in prostate
disease.
dosing and patient counseling. Also, E2 levels
can be held in check or lowered by compound-
ing aromatase-inhibitors such as anastrazole or
letrazole into the lower doses that men require,
rather than their more potent versions for fe-
male patients. Nutraceuticals such as omega-3
fatty acids, vitamin D, zinc, and selenium all
play an important role in prostate health, as
these agents have 5α-reductase inhibiting and
anti-inflammatory properties.24 More than
anything else, we see that the pathophysiol-
ogy of PCa, although quite complex, is being
explored at an amazing rate. I believe that
hormonal balance is critical, and that it is
largely hormonal imbalance that is involved
in prostate disease. In that regard, we must
conclude that the levels of T, E2, and DHT
experienced at a more youthful age are vital if
we are to improve prostate health.
Acknowledgment
The author expresses his appreciation to Ja-
son Tam, a student at the University of Hous-
ton College of Pharmacy, Houston, Texas, for
his tremendous assistance in preparing this
article while serving as an intern at Profes-
sional Compounding Centers of America.
References
1. Morgentaler A. Testosterone therapy in
men with prostate cancer: Scientific and
ethical considerations. J Urol 2009; 181(3):
972–979.
International Journal of Pharmaceutical Compounding
104 Vol. 14 No. 2 | March/April 2010
2. Cabeza M, Bratoeff E, Heuze I et al. New
progesterone derivatives as inhibitors of
5alpha-reductase enzyme and prostate
cancer cell growth. J Enzyme Inhibit Med
Chem 2006; 21(4): 371–378.
3. Huggins C, Hodges CV. Studies on pros-
tatic cancer: I. The effect of castration, of
estrogen and of androgen injection on se-
rum phosphatases in metastatic carcinoma
of the prostate. 1941. J Urol 2002; 168(1):
9–12.
4. Roddam AW, Allen NE, Appleby P et al.
Endogenous Hormones and Prostate Can-
cer Collaborative Group. Endogenous sex
hormones and prostate cancer: A collab-
orative analysis of 18 prospective studies. J
Natl Cancer Inst 2008; 100(3): 170–183.
5. Morgentaler A, Bruning CO III, DeW-
olf WC. Occult prostate cancer in men
with low testosterone levels. JAMA 1996;
276(23): 1904–1906.
6. Rhoden EL, Morgentaler A. Risks of
testosterone-replacement therapy and
recommendations for monitoring. N Engl J
Med 2004; 350(5): 482–492.
7. Morales A. Androgen replacement therapy
and prostate safety. Eur Urol 2002; 41(2):
113–120.
8. Slater S, Oliver RT. Testosterone: Its role
in development of prostate cancer and
potential risk from use as hormone re-
placement therapy. Drugs Aging 2000; 17(6):
431–439.
9. Kuiper GG, Enmark E, Pelto-Huikko M et
al. Cloning of a novel receptor expressed
in rat prostate and ovary. Proc Natl Acad Sci
USA 1996; 93(12): 5925–5930.
10. Bosland MC. Sex steroids and prostate
carcinogenesis: Integrated, multifactorial
working hypothesis. Ann N Y Acad Sci 2006;
1089: 168–176.
11. Friedman AE. Can a single model explain
both breast cancer and prostate cancer?
Theor Biol Med Model 2007; 4: 28.
12. Maggiolini M, Recchia AG, Carpino A et
al. Oestrogen receptor beta is required for
androgen-stiumlated proliferation of LN-
CaP prostate cancer cells. J Mol Endocrinol
2004; 32(3): 777–791.
13. Singh PB, Matanhelia SS, Martin FL. A
potential paradox in prostate adenocar-
cinoma progression: Oestrogen as the
initiating driver. Eur J Cancer 2008; 44(7):
928–936.
14. Morgentaler A. Testosterone deficiency
and prostate cancer: Emerging recognition
of an important and troubling relationship.
Eur Urol 2007; 52(3): 623–625.
15. Narayanan NK, Nargi D, Horton L et al.
Inflammatory processes of prostate tissue
microenvironment drive rat prostate car-
cinogenesis: Preventive effects of cele-
coxib. Prostate 2009; 69(2): 133–141.
16. Yatkin E, Bernoulli J, Talvitie EM et al.
Inflammation and epithelial alterations
in rat prostate: Impact of the androgen to
oestrogen ratio. Int J Androl 2009; 32(4):
399–410.
17. Ellem SJ, Risbridger GP. Aromatase and
regulating the estrogen:androgen ratio in
the prostate gland. J Steroid Biochem Mol
Biol 2009; [In print].
18. Maggio M, Basaria S, Ceda GP et al. The
relationship between testosterone and mo-
lecular markers of inflammation in older
men. J Endocrinol Invest 2005; 28(11 Suppl
Proceedings): 116–119.
19. Crawford ED, Andriole GL, Marberger
M et al. Reduction in the risk of prostate
cancer: Future directions after the Prostate
Cancer Prevention Trial. Urology 2009; [In
print].
20. Vickers AJ, Savage CJ, Lilja H. Finasteride
to prevent prostate cancer: Should all men
or only a high-risk subgroup be treated? J
Clin Oncol 2010; [In print].
21. Mostaghel EA, Geng L, Holcomb I et al.
Variability in the androgen response of
prostate epithelium to 5(alpha)-reductase
inhibition: Implications for prostate cancer
chemoprevention. Cancer Res 2010; 70(4):
1286–1295.
22. Scaglione F, Lucini V, Pannacci M et
al. Comparison of the potency of differ-
ent brands of Serenoa repens extract on
5alpha-reductase types I and II in prostatic
co-cultured epithelial and fibroblast cells.
Pharmacology 2008; 82(4): 270–275.
23. Frye CA, Koonce CJ, Edinger KL et al.
Androgens with activity at estrogen recep-
tor beta have anxiolytic and cognitive-
enhancing effects in male rats and mice.
Horm Behav 2008; 54(5): 726–734.
24. Isbam H, Pinthus JH, Marks LS et al. Tes-
tosterone and prostate cancer: Revisiting
old paradigms. Eur Urol 2009; 56(1): 48–56.
25. Trottier G, Boström PJ, Lawrentschuk N
et al. Nutraceuticals and prostate cancer
prevention: A current review. Nat Rev Urol
2010; 7(1): 21–30.
Address correspondence to Bruce Biundo, BS, RPh,
Professional Compounding Centers of America,
9901 South Wilcrest, Houston, TX 77099. E-mail:
bbiundo@pccarx.com
www.ijpc.com
 Feature
Determining the Causes of
Erectile Dysfunction:
Can Medications be a Double-Sided Sword?

LaVonn A. Williams
International Journal of
Pharmaceutical Compounding
Edmond, Oklahoma

Abstract
Like other medical problems, diagnosing the causes of erectile dysfunction requires a series of
tests, as well as trial and error.The possibility that side effects to a patient’s medications may be
one of the causes of erectile dysfunction is discussed often in published articles. Physicians are
aware that in order to diagnose a physiological problem, the simplest causes for the problem
should be considered and eliminated first. Therefore, the physician should review a patient’s list
of medications as first protocol.This article lists some of the more common causes of erectile dys-
function and provides a list of drugs that are linked to erectile dysfunction. Compounding phar-
macists should be involved in the treatment of this physiological/psychological condition to of-
fer private consultations and alternative medications to those patients who can’t or shouldn’t
take certain manufactured drugs that may cause erectile dysfunction or, because of certain risks,
drugs that are sold to treat erectile dysfunction.

O nce considered a subject that was too

personal or embarrassing, you can’t
turn on the television or the radio without
hearing an infomercial, commercial, or discus-
sion about erectile dysfunction (ED). In fact,
the International Journal of Pharmaceutical
Compounding has published many articles on
men in the U.S. and Europe suffering from
erectile dysfunction,1 clearly this is an issue
that will continue to be discussed, researched,
the subject of ED. With as many as 50 million and covered in publications, and new drugs

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 105
Feature
will continue to be manufactured, compounded, and sold to treat this
health problem.
ED can be a total inability to achieve erection, an inconsistent ability
to do so, or a tendency to sustain only brief erections.2 The Mayo Clinic
defines ED as the inability to maintain an erection sufficient for sexual
intercourse at least 25 percent of the time.3 Although ED is more com-
mon in older men, the problem can occur at any age. Formerly referred
to as (male) impotence and also referred to as sexual dysfunction, ED is
discussed in both the physiological and psychological fields. There are
many causes attributed to ED, but simply put, the male sexual arousal is a
complex process involving the brain, hormones, emotions, nerves, muscles,
and blood vessels. If something affects any of these systems, or the delicate
balance among them, ED can result. Although statistics vary, most indicate
that the causes of ED are physiological rather than psychological. At one
time, physicians attributed ED solely to psychological issues, but research
has proven this to be untrue. However, since sexual arousal involves
the brain, it cannot be denied that there are psychological causes of ED
including3:
• Anxiety
• Depression
• Fatigue
• Poor communication or conflict with your partner
• Stress
Regardless of the cause, a man’s self-image is a strong factor in the
decision to seek physiological/psychological advice for the treatment
of ED. According to the National Ambulatory Medical Care Survey
(NAMCS), in 1985, for every 1,000 men in the U.S., 7.7 physician office
visits were made for ED.2 By 1999, that rate had nearly tripled to 22.3.2
Although the increase in those patients seeking medical attention was
gradual, the numerous treatment options and the acceptance of openly
discussing this physiological problem was a large factor in the increased
number of men seeking advice. Although not without risk and, therefore,
not for every patient, one of the major factors for the increase in the
number of patients seeking advise for ED was the introduction of Viagra
in March 1998.2 NAMCS reported an estimated 2.6 million mentions
of Viagra at physician office visits in 1999; one-third of those mentions
occurred during visits for a diagnosis other than ED.2
Many publications attribute ED to a chronic health problem, includ-
ing the following3:
• Atherosclerosis (clogged blood vessels)
• Diabetes
• Heart disease
• High blood pressure
• Metabolic syndrome
• Obesity
Other causes and/or risk factors that can contribute to ED include3:
• Age
• Certain prescription medications
• Hormonal disorders such as low testosterone (hypogonadism)
• Multiple sclerosis
• Parkinson’s disease
• Peyronie’s disease
• Prolonged bicycling
• Substance abuse (e.g., alcoholism, smoking, marijuana)
International Journal of Pharmaceutical Compounding
106 Vol. 14 No. 2 | March/April 2010
• Surgeries or injuries that affect the pelvic area or spinal cord
• Treatments for prostate cancer
The purpose of this article is not to discuss nor debate published
literature on the physiological versus the psychological causes of ED nor
to discuss in detail the anatomical issues related to ED, but to discuss
one of the causes that was continuously revealed in the research as a
very possible cause of ED—side effects to certain medications (see the
accompanying Table). Physicians are aware that in order to diagnose
a physiological problem, the simplest causes for the problem should
be considered and eliminated first. Therefore, the physician should
review a patient’s list of medications as first protocol. Of course, we are
in no way insinuating that the answer to the cause of every patient’s
ED is simply in his medicine cabinet, nor are we insinuating that it is
an easy task to determine which, if any, medicines may be causing ED.
But, again, with so many available medicinal options, discontinuing and
trying different medications as trial and error to diagnose the cause of a
patient’s ED is much less invasive and less costly than the clinical tests
that are used to diagnose ED, including4:
• Corpus cavernosometry • Nocturnal penile tumescence
• Digital subtraction angiography • Penile angiogram
• Duplex ultrasound • Penile biothesiometry
• Dynamic infusion cavernosometry • Penile nerves function
• Magnetic resonance angiography
Since standard Medicare prescription drug coverage doesn’t cover
medications for erectile dysfunction, patients shouldn’t feel obligated
to take only manufactured drugs. A compounding pharmacist is more
likely to be able to prepare a drug that can treat and/or relieve ED than
a “one-size-fits-all” manufactured drug. Moreover, compounding phar-
macists offer private consultations to suggest alternative therapies for the
patient to present to their physician.
Conclusion
Like other medical problems, diagnosing the causes of erectile dys-
function requires a series of tests, as well as trial and error. The possibil-
ity that side effects to a patient’s medications may be one of the causes of
erectile dysfunction is discussed often in published articles. Physicians
are aware that in order to diagnose a physiological problem, the simplest
causes for the problem should be considered and eliminated first. There-
fore, the physician should review a patient’s list of medications as first
protocol. This article lists some of the more common causes of erectile
dysfunction and provides a list of drugs that are linked to erectile dys-
function. Compounding pharmacists should be involved in the treatment
of this physiological/psychological condition to offer private consulta-
tions and alternative medications to those patients who can’t or shouldn’t
take certain manufactured drugs that may cause erectile dysfunction or,
because of certain risks, drugs that are sold to treat erectile dysfunction.
References
1. [No author listed.] Erectile Dysfunction Facts. Information on E.D.
[E.D. Facts Website.] 2005. Available at: www.erectiledysfunction-
facts.com. Accessed January 13, 2010.
2. [No author listed.] National Institute of Diabetes and Digestive and
Kidney Diseases. National Institutes of Health of the U.S. Depart-
ment of Health and Human Services. Erectile Dysfunction. NIH
www.ijpc.com

Table. Drugs Linked to Erectile Dysfunction.5
Brand
Type Generic Name Name Type Generic Name Name
of Drug of Drug of Drug
Antiarrythmics Disopyramide Norpace
Antidepressants Amitriptyline Elavil
Anti-anxiety drugs/ Amoxipine Asendin
Antiepileptic drug Buspirone Buspar
Chlordiazepoxide Librium
Clomipramine Anafranil
Clorazepate Tranxene
Desipramine Norpramin
Diazepam Valium
Doxepin Sinequan
Fluoxetine Prozac Metoprolol Lopressor
Imipramine Tofranil
Isocarboxazid Marplan
Lorazepam Ativan
Nortriptyline Pamelor
Oxazepam Serax
Phenelzine Nardil
Phenytoin Dilantin Maxide
Sertraline Zoloft
Tranylcypromine Parnate Isoptin
Antihistamines Dimehydrinate Dramamine
Diphenhydramine Benadryl
Hydroxyzine Vistaril
Meclizine Antivert
Promethazine Phenergan
Chemotherapy Busulfan Myleran
medications Cyclophosphamide Cytoxan
Diuretics and Atenolol Tenormin
antihypertensives Bumetanide Bumex
Captopril Capoten
Chlorthalidone Hygroton
Clonidine Catapres
Enalapril Vasotec
Furosemide Lasix
Guanfacine Tenex
Hydralazine Apresoline
Publication No. 06-3923. [NIDDK. NIH Website.] December 2005.
Available at: http://kidney.niddk.nih.gov/kudiseases/pubs/impo-
tence. Accessed January 13, 2010.
3. [No author listed.] Mayo Foundation for Medical Education and
Research. Erectile Dysfunction. Document DS00162. [MayoClini.
com Website.] January 28, 2008. Available at: www.mayoclinic.com/
health/erectile-dysfunction/DS00162. Accessed January 13, 2010.
4. [No author listed.] Wikipedia. Erectile Dysfunction. [Wikipedia Web-
site.] Available at: http://en.wikipedia.org/wiki/Erectile_dysfunc-
tion. Accessed January 13, 2010.
www.ijpc.com
Feature
Brand
of Drug of Drug of Drug
Diuretics and Hydrochlorothiazide Esidrix
antihypertensives HydroDIURIL
continued Hydropres
Inderide
Lotensin
Moduretic
Oretic
Lotensin
Labetalol Normodyne
Methyldopa Aldomet
Nifedipine Adalat
Procardia
Phenoxybenzamine Dibenzyline
Propranolol Inderal
Spironolactone Aldactone
Triamterene Dyazide
Verapamil Calan
Verelan
Histamine H2-receptor Cimetidine Tagamet
antagonists Ranitidine Zantac
Muscle relaxants Cyclobenzaprine Flexeril
Orphenadrine Norflex
Nonsteroidal anti- Naproxen Anaprox
inflammatories Naprelan
Naprosyn
Indomethacin Indocin
Parkinson’s disease Benztropine Cogentin
medications Biperiden Akineton
Bromocriptine Parlodel
Levodopa Sinemet
Procyclidine Kemadrin
Trihexyphenidyl Artane
Prostate cancer Flutamide Eulexin
medications Leuprolide Lupron
5. [No author listed.] WebMD. Drugs Linked to Erectile Dysfunction.
[WebMD Website.] Available at: www.webmd.com/erectile-dysfunc-
tion/guide/drugs-linked-erectile-dysfunction. Accessed January 13,
2010.
Address correspondence to Loyd V. Allen, Jr., PhD, RPh, International Journal of
Pharmaceutical Compounding, 122 North Bryant Avenue, Edmond, OK 73034.
E-mail: lallen@ijpc.com
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 107
 Feature
Coenzyme Q10 Supplementation in the

Treatment of Heart
Disease
Bethany L. Bramwell, BS Pharm, RPh
Walgreens
West Plains, Missouri

Abstract
Significant deficiencies in coenzyme Q10
have been documented in a wide variety
of diseases in both animal and human
studies. Known predominately for its func-
tions as an antioxidant and membrane
stabilizer, coenzyme Q10 supplementa-
tion also has been demonstrated to ef-
fectively lower blood pressure, decrease
total cholesterol and low-density lipopro-
tein cholesterol, increase levels of high-
density lipoprotein cholesterol, and de-
crease symptoms of dyspnea, peripheral
edema, enlarged liver, and insomnia.The
majority of clinical work with coenzyme
Q10 in the past two decades has focused
on its role in heart disease. While usually
found in high concentrations in heart mus-
cle cells, both serum and tissue levels of
coenzyme Q10 are often lower in people
with congestive heart failure.The severity
of coenzyme Q10 deficiency is directly re-
lated to the severity of heart failure. Cor-
recting deficits in coenzyme Q10 in heart
failure patients can mitigate or reverse
myocardial dysfunction and necrosis.The
addition of coenzyme Q10 to conventional
treatments in congestive heart failure pa-
tients has been shown to improve quality
of life and decrease hospitalization rates.
In an effort to improve outcomes in pa-
tients supplemented with coenzyme Q10,
various delivery mechanisms to improve
the bioavailability of coenzyme Q10 are
currently under investigation.

International Journal of Pharmaceutical Compounding www.ijpc.com

108 Vol. 14 No. 2 | March/April 2010

Heart disease is the leading cause of morbidity and mortality in the U.S.1
Oxidative stress appears to play a vital role in atherosclerosis and heart fail-
ure.2 Evidence supports the adjunctive use of the antioxidant coenzyme Q10
(CoQ10) with conventional therapy in congestive heart failure (CHF), primary
hypertension, and myocardial infarction (MI). In an effort to improve out-
comes in patients supplemented with CoQ10, various drug delivery systems
are currently under investigation to improve bioavailability of CoQ10.
History
In 1957, Dr. Frederick Crane isolated a novel vitamin-like compound
from beef heart mitochondria.3 Having found the same substance from
vitamin-A-deficient rat liver, Professor Morton of England proposed the
name ubiquinone for the ubiquitous quinone we know as CoQ10. The
following year, researchers at Merck, Inc. determined the exact chemical
structure of CoQ10 as 2,3 dimethoxy-5 methyl-6 decaprenyl benzoquinone
and developed a process to synthesize it by fermentation. By the mid-1960s,
Professor Yamamura of Japan became the first to use CoQ7 (closely related
to CoQ10) for CHF in humans. In 1972, researchers documented CoQ10 de-
ficiency in human heart disease. By the mid-70s, the Japanese perfected the
large-scale technology required to produce pure CoQ10 in mass quantities,
paving the way for large clinical trials. With the ability to obtain pure CoQ10
and the technology to directly measure blood and tissue levels, the number
and size of clinical trials grew in the early 1980s.
Mechanism of Action
CoQ10 is a vitamin-like compound consisting of a quinone ring with
five-carbon isoprenoid attachments. CoQ10 is more prevalent in humans,
whereas CoQ6, CoQ7, CoQ8, and CoQ9 are higher in other species.4 CoQ10
is present in virtually all cells, but the highest concentrations are found in
mitochondria of cells in the heart, liver, kidneys, and pancreas. While CoQ10
behaves like a fat-soluble vitamin, it is normally produced in adequate
amounts endogenously and, therefore, does not meet the definition of a true
vitamin. CoQ10 is known predominately for its functions as an antioxidant
and membrane stabilizer, but it is a required cofactor in the mitochondrial
generation of adenosine triphosphate (ATP) in the oxidative respiration
pathway.
Prevention of oxidative damage, increased ATP synthesis,5 decreases
in free radicals, and membrane protection appear to be the primary
mechanisms of CoQ10’s benefits in heart failure and angina. CoQ10 also
lowers total peripheral resistance and systolic blood pressure.4 This effect
is theorized to occur by endothelium-independent arterial relaxation and
endothelium-dependent vasodilation caused by increases in endothelial
production of prostacyclin (PGI2) and/or increased sensitivity of arterial
smooth muscle to PGI2.
CoQ10 also decreases total cholesterol and low-density lipoprotein (LDL)
cholesterol, while increasing levels of high-density lipoprotein (HDL) cho-
lesterol and circulating levels of vitamins E and C.
CoQ10 Deficiency
Significant deficiencies in CoQ10 have been documented in a wide vari-
ety of diseases in both animal and human studies. CoQ10 levels are lower
in the elderly and in those with chronic diseases, including heart disease,
cancer, diabetes, HIV/AIDS, Parkinson’s, and muscular dystrophies.4,5
The biosynthesis of CoQ10 is highly complex and requires at least seven
vitamins, including B2, B6, B12, C, pantothenic acid, and folic acid, as well
as trace minerals.3 Due to these prerequisites, the endogenous process of
CoQ10 is highly vulnerable to dietary insufficiencies.
CoQ10 deficiencies can also result from pharmacological or physiological
impairment of CoQ10 biosynthesis or excessive utilization of CoQ10 by the
www.ijpc.com
Feature
body. Due to a partially shared biogenesis pathway, the cholesterol block-
ing action of HMG-CoA reductase inhibitors results in inhibition of CoQ10
production. This is of particular importance in heart failure patients—many
of which are prescribed statins on top of a preexisting CoQ10 deficiency.
CoQ10 in Heart Disease
Despite considerable advances in pharmacological therapy over the
years, morbidity and mortality remain high in heart failure patients.6 This
may be due, in part, to the inadequacy of current regimens to fully consider
the unique energy requirements of the heart. The majority of clinical work
with CoQ10 in the past two decades has focused on its role in heart disease.
While usually found in high concentrations in heart muscle cells, both serum
and tissue levels of CoQ10 are often lower in people with CHF.2 The severity
of CoQ10 deficiency is directly related to the severity of heart failure.
It is unknown whether CoQ10 deficiency is a primary or secondary
etiologic factor in heart disease. Regardless, increased oxidative stress in
heart failure results in excess consumption of CoQ107 and supplementation
with CoQ10 in patients with heart disease appears to prevent oxidative dam-
age. Correcting deficits in CoQ10, as well as other micronutrients including
l-carnitine, thiamine, and amino acids like taurine, in heart failure patients
can mitigate or reverse myocardial dysfunction and necrosis.6 The addition
of CoQ10 to conventional treatments in CHF patients has been shown to im-
prove quality of life and decrease hospitalization rates.2 Symptoms of dysp-
nea, peripheral edema, enlarged liver, and insomnia also are decreased in
patients supplemented with CoQ10. Previous research did not indicate that
CoQ10 improved ejection fraction or exercise tolerance in these patients;4
however, newer evidence opposes these past findings. Patients who begin
CoQ10 soon after the onset or diagnosis of CHF see the most improvement
in heart function.2 In contrast, when supplemented with CoQ10, patients with
progressed disease still demonstrate some improvement but do not see a
return to normal heart function.
Current evidence supports using CoQ10 as an adjunctive therapy to
conventional treatment in CHF. Concurrent with previous studies on myo-
cardial CoQ10 depletion in heart failure, CoQ10 plasma levels appear to be an
independent predictor of patient survival.8 Given along with conventional
therapy, CoQ10 results in an improved ejection fraction and increased cardiac
output. In doses ranging from 60 to 200 mg/day, researchers have concluded
that CoQ10 significantly improves systolic function in chronic heart failure.
Its effectiveness may actually be diminished, however, with concomitant use
of current standard therapies, specifically ACE inhibitors.9 The ongoing Q-
SYMBIO trial, studying CoQ10 as an adjunctive therapy, will address whether
CoQ10 supplementation improves survival in CHF patients.7
Studies have demonstrated that CoQ10 supplementation can also
effectively lower blood pressure. Taking CoQ10 along with antihyperten-
sives seems to provide additional reductions in both systolic and diastolic
pressure. This effect might allow for the dose reduction or discontinuation
of some antihypertensive medications.4 In patients with isolated systolic
hypertension, CoQ10 can lower the systolic pressure by about 26%.
CoQ10 has also demonstrated effectiveness in preventing a second MI. If
initiated within 72 hours post-MI, CoQ10 also has been shown to decrease
the risk of cardiac events including nonfatal MI and cardiac death in patients
at risk for atherothrombosis.4
Statin-induced CoQ10 Deficiencies
Statin therapy has not demonstrated improved outcomes in CHF pa-
tients, and CoQ10 depletion may be the reason.8 Statins work by inhibiting
the conversion of HMG-CoA to mevalonate, an early and rate-limiting step
in the biosynthesis of cholesterol.10 A branch of the mevalonate choles-
terol biosynthetic pathway leads to CoQ10 formation. Heart failure patients
treated with statins for 12 months or longer have demonstrated CoQ10
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 109
Feature
Rx
Coenzyme Q10 50-mg in
Polyethylene Glycol 1450 Troche
For 24 troches
Coenzyme Q10 1.2
Stevia 480
Silica gel 240
Xanthan gum 400
Polyethylene glycol 1450 22.5
Flavor qs
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Triturate the first four powders together and mix well.
4. Melt the polyethylene glycol 1450 at 50ºC and slowly add the
powders while stirring.
5. Remove from heat, add the flavor, and mix well.
6. Pour into molds, cool, and smooth the surface as needed.
7. Package and label.
STABILITY
A beyond-use date of up to 6 months can be used for this preparation.
Rx
Coenzyme Q10 10-mg/mL in MCT
Anhydrous Vehicle
For 100 mL
Coenzyme Q10 1
Sugar, confectioner’s 30
Benzoic acid 100
Silica gel 100
Flavor qs
Medium-chain Triglycerides qs 100
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Add the coenzyme Q10 to about 70 mL of the medium-chain
triglycerides, followed by the confectioner’s sugar, benzoic acid,
and colloidal silicon dioxide (silica gel); mix well after each addi-
tion.
4. Add the flavor and mix well.
5. Add sufficient medium-chain triglycerides to final volume and
mix well.
6. Package and label.
STABILITY
A beyond-use date of up to 6 months can be used for this preparation.
International Journal of Pharmaceutical Compounding
110 Vol. 14 No. 2 | March/April 2010
levels 20% lower than baseline.3 In addition, higher doses of statins reduce
CoQ10 in the liver and LDL-bound CoQ10.
Studies have shown that the use of statins for the prevention of athero-
sclerotic outcomes in ischemic heart failure patients does not have a benefi-
cial effect.11 In addition to the deleterious effects of statins on CoQ10 levels,
significant increases in collagen turnover indicators, which can contribute to
cardiac fibrosis, are seen with prolonged statin use. Researchers have con-
cluded that any purported beneficial outcomes of statin therapy on cardiac
g remodeling in heart failure patients are likely negated by these effects.
mg Clinicians have long reported that adverse effects from statin therapy
mg are higher than reported in the literature. A study at the East Texas Medical
mg Center in Tyler found that out of fifty new cardiology patients on statin
g therapy for an average of 28 months, all demonstrated one or more adverse
effects including myalgia, fatigue, dyspnea, memory loss, and peripheral
neuropathy.12 After discontinuation of the statin and initiation of CoQ10
therapy at an average of 240 mg/day, complaints of fatigue decreased from
84% to 16%, myalgia from 64% to 6%, and dyspnea from 58% to 12%.
The effects of statins on CoQ10 levels have long been known to the
pharmaceutical industry. In 1990, Merck, Inc. sought and received a patent
for combination statin/CoQ10 formulations for the prevention of statin-as-
sociated myopathy.10 To date, no combination product has come to market,
and no warning regarding potential detrimental effects of CoQ10 deficiency
appears in product labeling for any of the statins.
CoQ10 Delivery Mechanisms
While CoQ10 is present in small quantities in meats and seafoods, these
amounts are not therapeutically significant.4 Because of the limited oral
bioavailability of CoQ10, various formulations of this supplement are under
investigation. Some clinicians recommend chewing the tablets with a fatty
meal to improve absorption,3 and studies also have shown that the oral
bioavailability of CoQ10 formulated in soybean oil is higher than in other
formulations.4 Formulations for oral administration consisting of a combina-
tion of oil, surfactant, and cosurfactant significantly increase the maximum
plasma concentration (Cmax) and area under the curve (AUC) for CoQ10.13
Chinese researchers have demonstrated that using nanoliposomes as an
oral delivery vehicle also can enhance the intestinal absorption of CoQ10.14
While effervescent and fast-melting tablets have demonstrated faster de-
g livery of CoQ10, they exhibit the same AUC when compared to current soft
g gelatin and powder-filled hard gelatin capsule formulations and, therefore,
mg their role in CoQ10 therapy should be further evaluated.15
mg Due to the poor water-solubility of CoQ10, the feasibility of developing
a transdermal delivery system (TDS) for CoQ10 is of considerable interest.
mL Researchers at the Ewha Womens University College of Pharmacy in Seoul,
Korea recently reported their research on using pressure-sensitive adhesives
for a CoQ10 TDS. Of the solution formulations studied, the addition of
unsaturated fatty acids including lauric acid, linoleic acid, and oleic acid to
a 60:40 solution of diethylene glycol monoethyl ether (DGME)/propylene
glycol monolaurate (PGML) demonstrated the highest permeation flux rates
for CoQ10.16 Rates of up to 9.3 mcg/cm2/hour were seen with the most
rapid permeability during the first 12 hours. The system containing 6%
oleic acid demonstrated the most preferential pharmacokinetics including a
lower Cmax, comparable AUC, and prolonged half-life and time to maximum
plasma concentration (Tmax) when compared to oral CoQ10 administration.
Researchers concluded that effective transdermal delivery of CoQ10 could
be obtained when formulated in either 6% linoleic acid or oleic acid in
60:40 DGME/PGML.
The Future of CoQ10
In addition to CoQ10 deficiency, hypertension, CHF, and the prevention
of MI, CoQ10 has been used and effectiveness documented in:
www.ijpc.com
 Feature

• Atrial fibrillation17
• Mitochondrial encephalomyopathies4
• HIV/AIDS
• Huntington’s disease
• Ischemic reperfusion injury
• Migraine headaches
• Muscular dystrophy
• Parkinson’s disease
In light of the recent research on CoQ10, the roles of many other mi-
cronutrients involved in heart function are being reviewed. The use of full-
spectrum antioxidant therapy, featuring a complementary array of natural
antioxidants and nutraceuticals including folate, CoQ10, pirulina, lipoic acid,
N-acetylcysteine, cocoa flavanols, and taurine is being studied to determine
effects on cardiac remodeling and overall heart function.6,17
Conclusion
As CoQ10 itself is not patentable, its lack of use, despite four decades of
research demonstrating consistent outcomes, lies not in the evidence but in
politics and economics. The evidence supports CoQ10 supplementation as
an adjunct to conventional therapy in CHF, and statin use in these patients
should be carefully considered. Clinicians should be aware of the interaction
between CoQ10 levels and statins and be vigilant to the possibility that statin
drugs may impair both skeletal muscle and myocardial function. In an effort
to improve outcomes in patients supplemented with CoQ10, various delivery
mechanisms to improve the bioavailability of CoQ10 are currently under
investigation.
adverse effects with supplemental Coenzyme Q10 and statin drug
discontinuation. Biofactors 2005; 25(1–4): 147–152.
13. Balakrishnan P, Lee BJ, Oh DH et al. Enhanced oral bioavailability of
Coenzyme Q10 by self-emulsifying drug delivery systems. Int J Pharm
2009; 374(1–2): 66–72.
14. Xia S, Xu S, Zhang X et al. Nanoliposomes mediate coenzyme Q10
transport and accumulation across human intestinal Caco-2 cell mono-
layer. J Agric Food Chem 2009; 57(17): 7989–7996.
15. Joshi SS, Sawant SV, Shedge A et al. Comparative bioavailability of two
novel coenzyme Q10 preparations in humans. Int J Clin Pharmacol Ther
2003; 41(1): 42–48.
16. Jung SY, Kang EY, Choi YJ et al. Formulation and evaluation of ubi-
decarenone transdermal delivery systems. Drug Dev Ind Pharm 2009;
35(9): 1029–1034.
17. McCarty MF. Practical prevention of cardiac remodeling and atrial fibril-
lation with full-spectrum antioxidant therapy and ancillary strategies.
Med Hypotheses 2010; [In print].
Address correspondence to Bethany L. Bramwell, BS Pharm, RPh, Compounding
Pharmacist, Walgreens District #306, Walgreens, 1010 Worley Drive, West Plains,
MO 65775. E-mail: bethany.bramwell@walgreens.com

References
1. Centers for Disease Control and Prevention. FastStats. Leading Causes of
Death. [CDC Website.] Available at: www.cdc.gov/nchs/FASTATS/lcod.
htm. Accessed January 24, 2010.
2. Singh U, Devaraj S, Jialal I. Coenzyme Q10 supplementation and heart
failure. Nutr Rev 2007; 65(6 Pt 1): 286–293.
3. Langsjoen P. Introduction to Coenzyme Q10. [University of Washington
Faculty Website.] Available at: http://faculty.washington.edu/ely/co-
enzq10.html. Accessed January 22, 2010.
4. [No author listed.] Coenzyme Q-10. [Natural Medicines Comprehensive
Database Website.] Available at: www.naturaldatabase.com. Accessed
January 22, 2010.
5. DerMarderosian A. Coenzyme Q-10. [Merck Website.] May 2009. Avail-
able at: www.merck.com/mmpe/sec22/ch331/ch331f.html. Accessed
January 23, 2010.
6. Soukoulis V, Dihu JB, Sole M et al. Micronutrient deficiencies: An unmet
need in heart failure. J Am Coll Cardiol 2009; 54(18): 1660–1673.
7. Mortensen SA. Adjunctive Therapy with Coenzyme Q10 in Heart Failure: Q-
SYMBIO Study Status. Available at: www.senpu.jp/coq10/pdf/j11-022.
pdf. Accessed January 24, 2010.
8. Molyneux SL, Florkowski CM, Richards AM et al. Coenzyme Q10:
An adjunctive therapy for congestive heart failure? N Z Med J 2009;
122(1305): 74–79.
9. Sander S, Coleman CI, Patel AA et al. The impact of coenzyme Q10 on
systolic function in patients with chronic heart failure. J Card Fail 2006;
12(6): 464–472.
10. [No author listed.] [Free Patents Online Website.] Available at: www.
freepatentsonline.com/4933165.html. Accessed January 23, 2010.
11. Ashton E, Windebank E, Skiba M et al. Why did high-dose rosuvastatin
not improve cardiac remodeling in chronic heart failure? Mechanistic
insights from the UNIVERSE study. Int J Cardiol 2010; [In print].
12. Langsjoen PH, Langsjoen JO, Langsjoen AM et al. Treatment of statin

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 111
 Feature
C ase R eport:

The Use of Inhaled Cyclosporine to

Treat Bronchiolitis Obliterans Syndrome
in a Lung Transplant Patient
Linda F. McElhiney, PharmD, RPh, FIACP,
FASHP
Clarian Health Partners, Inc.
Indianapolis, Indiana

ABSTRACT
The first lung transplantation was performed
successfully in 1983 and has become a vi-
able option for end-stage pulmonary dis-
ease. Advances in surgical techniques, the
development of better immunosuppressive
agents, and the standardization of care have
improved patient survival and quality of life.
This article includes statistics on men versus
women diagnosed with Chronic Obstructive
Pulmonary Disease. Included with this article
is a case report of a 52-year-old white male
who had undergone a bilateral lung trans-
plant.The patient’s medication protocol is dis-
cussed within this article, including the use
of inhaled cyclosporine to treat acute cellu-
lar rejection, one of the major complications
associated with lung transplantation. The
formulation for the cyclosporine for aerosol
that was prepared by a compounding phar-
macist is included with this article.

International Journal of Pharmaceutical Compounding www.ijpc.com

112 Vol. 14 No. 2 | March/April 2010

CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
Chronic Obstructive Pulmonary Disease (COPD), a slowly progres-
sive disease of the respiratory system that is characterized by a gradual
loss of lung function, is the fourth leading cause of death in the U.S.1
Sidebar 1 lists some information and statistics about COPD. COPD is a
general term used to describe several respiratory diseases:
• Chronic bronchitis
• Chronic obstructive bronchitis
• Emphysema
• Combinations of these conditions
SIDEBAR 1
Chronic Obstructive Pulmonary Disease
Facts1
Prevalence
• Highest prevalence of emphysema in white males
and lowest in black females
• Higher prevalence of chronic bronchitis in females
than males
• 12.1 million adults ages 25 and older reported diagno-
sis of Chronic Obstructive Pulmonary Disease in
2001
Mortality
• The age-adjusted Chronic Obstructive Pulmonary
Disease death rate was about 46% higher in males
than females and 63% higher in whites than blacks
• Chronic Obstructive Pulmonary Disease death rate
for females more than doubled between 1980 and
2000
• Chronic Obstructive Pulmonary Disease is projected
to be the third leading cause of death for both males
and females by the year 2020
The largest risk factor for developing COPD is cigarette smoking;
although other types of tobacco smoking will increase the risk. Other
documented causes of COPD include occupational exposure to dusts
and chemicals. Currently, there is no known cure for COPD, and the
treatment is usually supportive to relieve symptoms and improve quality
of life for the patient. The symptoms of COPD can become severe and
life threatening. In adults, COPD is the common reason attributed to
lung transplantation.
The first lung transplantation was performed successfully in 1983 and
has become a viable option for end-stage pulmonary disease. Sidebar
2 provides a list of common diseases that may require transplantation.
Advances in surgical techniques, the development of better immunosup-
pressive agents, and the standardization of care have improved patient
survival2 (see sidebar 3 for survival statistics) and quality of life. Lung
transplantation involves removing a patient’s diseased lung and replac-
ing it with a healthy lung from a deceased donor or healthy lobes from
www.ijpc.com
Feature
SIDEBAR 2
Diseases that May Require Lung
Transplantation Based on Severity of
Disease
• Chronic Obstructive Pulmonary Disease (more
common in adults)
• Cystic fibrosis (more common in children)
• Idiopathic pulmonary fibrosis
• Pulmonary hypertension
• Alpha-1 antitrypsin deficiency
SIDEBAR 3
Single-Lung Transplantation Survival
Rates from 20052
• More than 82% of patients survive the first year
• Nearly 60% survive 3 years
• More than 43% survive 5 years
a couple of living donors. Of the possible transplantations (e.g., kidney,
heart), lung transplantations are less common due to the small number
of donors available. Lung transplantations are reserved for patients who
are likely to die from lung disease within one to two years.
There are major complications associated with lung transplantation,
mainly rejection and infection. Rejection most commonly occurs within
the first six months of the transplant. Treatment protocols for acute
cellular rejection and postoperative infections have improved; however,
chronic allograft rejection or bronchiolitis obliterans syndrome (BOS) is
a devastating complication of lung transplantation and the leading cause
of death in 50% of lung transplant patients.3 Treatment usually involves
increasing immunosuppression with various agents, but improvement
occurs only in 50% of affected patients. Increasing the dose of immu-
nosuppressive drugs frequently results in toxicity from the drugs and
opportunistic infection. Patients with BOS who do not respond to treat-
ment eventually succumb to progressive respiratory failure.
Cyclosporine
Cyclosporine is an immunosuppressive agent that is commercially
available as a capsule, oral solution, or parenteral product. It blocks
lymphocyte activation by inhibiting transcription of cytokine genes. Oral
absorption may be erratic in some patients, making dosing and achiev-
ing therapeutic levels difficult. Unfortunately, cyclosporine has a narrow
therapeutic index which can cause some serious adverse effects such as:
• Encephalopathy
• Hepatotoxicity
• Hyperkalemia
• Hypertension
• Microangiopathic hemolytic anemia
• Nephrotoxicity
• Thrombocytopenia
An off-label use of cyclosporine has been investigated since the early
1990s as a treatment for chronic rejection, persistent acute rejection,
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 113
Feature

BOS, and for prophylactic use.4 Aerosolized cyclosporine (aCsA) was

developed based on the rationale that high concentrations of the drug Table. Blood Levels on Aerosolized
delivered directly to the lung tissue by inhalation would result in de- Cyclosporine and Oral Cyclosporine for
creasing rejection while limiting systemic side effects. Studies by Keenan
et al5 and Burkart et al6 demonstrate this rationale and describe the
Patient SC.
preparation of the aCsA. The following case report, which represents Date Cyclosporine Blood Level (ng/mL)
the conclusion to this article, is an example of the use of cyclosporine in (Therapeutic Range: 150 to 400 ng/mL)
a patient who had undergone a bilateral lung transplant.
2/12 251
2/13 163
CASE REPORT 2/14 147
SC, a 52-year-old white male, was admitted to the hospital after a
bronchoscopy showed acute cellular rejection. A bronchoaveolar lavage 2/15 179
(BAL) culture revealed Mycobacterium gordonii. The patient underwent 2/16 161
a bilateral lung transplant six months prior to his admission. He had 2/17 155
undergone therapy for the rejection with methylprednisolone, as well as 2/26 145
undergoing prophylaxis for his cytomegalovirus (CMV) mismatch with
valganciclovir and CytoGam. Treatment course was complicated and, 3/09 212
since the transplant, severe tracheal stenosis required stent placement. 3/23 190
He also had a history of colonization with methicillin-resistant Staphy- 4/15 228
lococcus aureus (MRSA). Inhaled cyclosporine was added to his treatment

for the acute cellular rejection. The Mycobacterium gordonii culture was
sent out for susceptibility testing for future reference in case the patient
developed an infection.
One month later, SC was readmitted to the hospital with com-
plaints of hypoxia, nausea, and vomiting. He was placed empirically on
intravenous tigecycline, and he underwent bronchoscopy. Cultures were
consistent with the colonized MRSA. He also had significant stenosis
of the bronchus intermedius, which was ballooned with good results.
The remainder of his hospital course was unremarkable. Before being
discharged, the patient was taught how to self-administer the inhaled
cyclosporine (see sidebar 4 to view this patient’s discharge summary).
The patient’s cyclosporine blood levels remained within therapeutic
range throughout the course of therapy, the levels of which are shown in
the accompanying Table.
When the physician ordered the aCsA for SC, a request was sent to
the compounding pharmacy laboratory for preparation. Bulk United
States Pharmacopeial-grade cyclosporine powder and propylene glycol
was obtained from Spectrum Chemical. Sterile, water-free, 5-mL vials
were also purchased. The aCsA solution was prepared according to
the study by Keenan et al (see the accompanying formulation). Upon
discharge, the patient was given a 30-day supply since he resided almost
four hours from the hospital.
According to the United States Pharmacopeia Chapter <797> standards,
aCsA is a high-risk sterile compound.7 Since the patient is on immuno-
suppressive therapy, the prepared batch and subsequent batches were
tested for sterility to ensure that there was no microbial contamination
during the compounding process. Each vial was visually inspected for
color (liquid should be colorless), particulate matter, and precipitation.
The pH was tested. A beyond-use date of 30 days was assigned to the
compound, which is conservative since the aCsA is a nonaqueous liquid
preparation.
Two months after the second discharge, SC presented for a presched-
uled bronchoscopy with complaints of fever, shortness of breath, cough,
“rattling,” chills, headache, and earache. He stated that he had been
doing well until three days prior to admission. A chest x-ray revealed
a new left lower lobe infiltrate. He was admitted with increased O2 re-
quirement, relative hypoxia, and MRSA pneumonia. Although the acute
Rx
Cyclosporine for Aerosol
300-mg/5-mL Liquid
For 50 mL
Cyclosprine 3 g
Propylene glycol 48 mL
Note: This formulation should be prepared according to strict aseptic com-
pounding technique in a laminar airflow hood in a cleanroom or via isolation
barrier technology by a compounding pharmacist who is validated in aseptic
compounding. This is a high-risk preparation.
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Pour the propylene glycol into a glass beaker.
4. Add the cyclosporine to the beaker and mix well to dissolve.
Note: The mixture should be clear.
5. Draw up the liquid from the beaker into a sterile syringe.
6. Attach an appropriate 0.22 micron filter with a sterile needle and
push the desired amount of liquid into each sterile, water-free
vial.
7. Seal and label each vial.
8. Send a sample to be tested for sterility.
PACKAGING
Package in sterile, water-free vials.
LABELING
Store at room temperature. For inhalation use only.
STABILITY
A beyond-use date of 30 days is appropriate for this preparation.

International Journal of Pharmaceutical Compounding www.ijpc.com

114 Vol. 14 No. 2 | March/April 2010
 Feature

SIDEBAR 4
Patient Discharge Summary Physical Assessment
Condition: Stable
Chief Complaint
• Nausea and vomiting Labs
• Hypoxia Cyclosporine blood level 160 ng/mL
• Acute rejection of allograft
Discharge Medications
Past Medical History • Aerosolized cyclosporine: 100 mg inhaled daily for
• Chronic Obstructive Pulmonary Disease status post 7 days, then every other day (pre-medicate with
bilateral lung transplantation Xopenex and Lidocaine 2%)
• Ischemic reperfusion injury and tracheal stenosis • Prednisone: 20 mg po daily
• Multifocal atrial tachycardia • Mycophenolate mofetil: 1 g po twice daily
• Osteoporosis • Cyclosporine: 150 mg po daily
• Diabetes • Septra SS: po every other day
• Hyperlipidemia • Nystatin: 5 mL swish-and-swallow twice daily
• Anxiety • Valganciclovir: 900 mg po twice daily
• Depression • Metoprolol: 50 mg po twice daily
• Methicillin-resistant Staphylococcus aureus airway colo- • Lisinopril: 5 mg po daily
nization • NovoLog: sliding scale
• Vasectomy • Pravastatin: 40 mg po at bedtime
• Obesity • Esomeprazole: 40 mg po daily
• Allergic rhinitis • Clonazepam: 1 mg po daily
• Citracal plus vitamin D: 700 mg po twice daily
Allergies • Alendronate: 70 mg po weekly
None • Aspirin: 81 mg po daily
• Centrum Silver
Social History • MiraLax: prn
Former smoker, occasional alcohol use. Worked in man- • Azithromycin: 250 mg po every other day
agement. Lives with son and girlfriend. • Advair: 250/50 mg twice daily
• Norco: prn
Family History • Colace: prn
Diabetes, hypertension, Graves disease (in siblings) • Senokot: prn

rejection was being controlled and stabilized by the aCsA and the other
immunosuppressives, the patient succumbed two months later from sep-
tic shock, acute respiratory distress syndrome, and MRSA pneumonia.
REFERENCES
1. U.S. Department of Health and Human Services. National Institutes of
Health. National Heart, Lung, and Blood Institute. Data Fact Sheet: Chronic
Obstructive Pulmonary Disease. [U.S. Department of Health and Human
Services Website.] March 2003. Available at: www.apsfa.org/docs/copd_fact.
pdf. Accessed January 15, 2010.
2. U.S. Department of Health and Human Services. National Institutes of
Health. National Heart, Lung, and Blood Institute. Diseases and Conditions
Index: Lung Transplant. [U.S. Department of Health and Human Services
Website.] Available at: www.nhlbi.nih.gov/health/dci/Diseases/lungtxp/
lungtxp_risk.html. Accessed January 15, 2010.
3. Garone S, Ross DJ. Bronchiolitis obliterans syndrome. Current Opinion in
Organ Transplantation 1999; 4(3): 254–263.
4. Iacono AT, McCurry KR, Corcoran TE. Inhalation cyclosporine: A new use
in lung transplantation? Current Opinion in Organ Transplantation 2003; 8(4):
327–333.
5. Kennan RJ, Iacono A, Dauber JH et al. Treatment of refractory acute al-
lograft rejection with aerosolized cyclosporine in lung transplant recipients.
J Thorac Cardiovasc Surg 1997; 113(2): 335–341.
6. Burkart GJ, Smaldone GC, Eldon MA et al. Lung deposition and pharma-
cokinetics of cyclosporine after aerosolization in lung transplant patients.
Pharm Res 2003; 20(2): 252–256.
7. United States Pharmacopeial Convention, Inc. USP Pharmacists’ Pharma-
copeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention, Inc.; 2008:
779–831.
Address correspondence to Linda F. McElhiney, PharmD, RPh, FIACP, FASHP,
Clarian Health Partners, Inc., 550 N. University Boulevard UH 1451, Indianapo-
lis, IN 46202. E-mail: lmcelhin@clarian.org

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 115
THE LEADER IN
COMPOUNDING
TRAINING
RESOURCES
PCCA provides the highest quality educational programming
available in the profession. From pediatric preparations to pain
management, compounding pharmacists have benefitted
from our knowledge and resources that help provide person-
alized solutions for patients with medication challenges.

We’re pleased to offer an exciting line-up of compounding

topics and top-notch speakers in 2010!

PCCA is a complete resource for high-quality

fine chemicals, equipment, accredited training
and education, facility workflow and design, as
well as pharmacy, management and marketing
consultation necessary for a successful com-
pounding practice.
© PCCA 2010
PCCAPCCA
CE Programs
CE Programs
and Training
and Training
Courses
Courses 2 02
1 0 1S0CSHCEH
DEUDL U
E LE
Aseptic Technique
Aseptic Technique
Compounding
Compounding
Course Course Sept. 16/General
Sept. 16/General
Compounding
Compounding
Webinar for
Webinar
Practitioners;
for Practitioners;
Nov. 18/ Nov. 18/
Houston, Texas
Houston,
• Two
Texas
and•1/2-day
Two andcourse
1/2-day course VeterinaryVeterinary
Webinar; Dec.
Webinar;
9 /Men’s
Dec. Health
9 /Men’s
Webinar
Health Webinar
Dates: Jan.
Dates:
27-29,
Jan.
Feb.
27-29,
22-24,
Feb.
March
22-24,
8-10,
March
June8-10,
7-9, June
July 21-23,
7-9, July 21-23,
Aug. 25-27,
Aug.
Oct.
25-27,
13-15,
Oct.
Nov.
13-15,
3-5, Nov. 3-5, PCCA Symposiums
PCCA Symposiums
- Houston,
- Houston,
Texas Texas
Dates/Event:
Dates/Event:
April 22-24/Anti-Aging/Cosmeceutical
April 22-24/Anti-Aging/Cosmeceutical
Hands-onHands-on
Symposium;Symposium;
USP <797>
USP Implementation
<797> Implementation
Aseptic Compounding
Aseptic Compounding
Course Course May 20-21/Marketing
May 20-21/Marketing
Symposium;Symposium;
Aug. 12-14/PK
Aug. 12-14/PK
Software 2nd
Software
Annual
2nd Annual
Houston, Texas
Houston,
• Two
Texas
and•1/2-day
Two andcourse
1/2-day course User Conference;
User Conference;
Aug. 30-31/Quality
Aug. 30-31/Quality
Assurance/Accreditation
Assurance/Accreditation
ReadinessReadiness
Date: MayDate:
5-7 May 5-7 SymposiumSymposium
Comprehensive
Comprehensive
Compounding
Compounding
Course (C
Course
3
) - USA
(C3NEW!
) - USA NEW! PCCA Quick-Ed
PCCA Quick-Ed
Half-DayHalf-Day
RegionalRegional
Events NEW!
Events NEW!
Houston, Texas
Houston,
• Four-day
Texas • course
Four-day course Dates/Location:
Dates/Location:
Feb. 20/Innovative
Feb. 20/Innovative
CompoundingCompounding
for Dentistry/Orlando,
for Dentistry/Orlando,
Fla.; Fla.;
Dates: Jan.
Dates:
18-21,
Jan.
Feb.
18-21,
15-18,Feb.
March
15-18,
22-25,
March
April
22-25,
12-15,
April
May 12-15,
17-20,
May 17-20, March 27/Developing
March 27/Developing
a Cosmeceutical
a Cosmeceutical
Niche/Dallas,
Niche/Dallas,
Texas; April
Texas;
17/ April 17/
July 12-15,July
Aug.12-15,
16-19,
Aug.
Sept.
16-19,
20-23,
Sept.
Nov.
20-23,
8-11,Nov.
Dec.8-11,
6-9 Dec. 6-9 Compounding
Compounding
for Cash infor
a Third
Cash Party
in a Third
World/Atlanta,
Party World/Atlanta,
Ga; May 22/Ga; May 22/
Compounding
Compounding
for Cash infor
a Third
Cash Party
in a Third
World/Detroit,
Party World/Detroit,
Mich.; JuneMich.;
12/ June 12/
Marketing
Marketing
Boot Camps
Boot NEW!
Camps NEW! DevelopingDeveloping
a Cosmeceutical
a Cosmeceutical
Niche/Memphis,
Niche/Memphis,
Tenn.; Aug. Tenn.;
14/Innovative
Aug. 14/Innovative
Houston, Texas
Houston,
• One-day
Texas •course
One-day course Compounding
Compounding
for Dentistry/Oklahoma
for Dentistry/Oklahoma
City, Okla.;City,
Aug. Okla.;
21/Compounding
Aug. 21/Compounding
for for
Dates: Jan.
Dates:
22, Feb.
Jan.19,
22,March
Feb. 19,
26,March
April 16,
26,July
April16,
16,Aug.
July20,
16, Aug. 20, Podiatry &Podiatry
Wound Care/Newport,
& Wound Care/Newport,
R.I.; Sept.R.I.;
25/Developing
Sept. 25/Developing
a Sports a Sports
Sept. 24, Nov.
Sept.12,
24,Dec.
Nov.10
12, Dec. 10 Medicine/Nutrition
Medicine/Nutrition
Niche/Phoenix,
Niche/Phoenix,
Ariz. Ariz.
PK Software
PK Software
Training Training Andropause/Men’s
Andropause/Men’s
Health Events
Health Events
Houston, Texas
Houston,
• One-day
Texas •course
One-day course Dates/Time:
Dates/Time:
May 20/Men’s
May Health
20/Men’s
Webinar
Health(7-8:30
Webinar
PM(7-8:30
CST); PM
Dec.CST);
9/Men’s
Dec. 9/Men’s
Dates: Jan.
Dates:
22, Feb.
Jan.19,
22,March
Feb. 19,
26,March
April 16,
26,May
April21,
16,July
May16,
21, July 16, Health Webinar
Health(7-8:30
WebinarPM(7-8:30
CST) PM CST)
Aug. 12-14Aug.
(Conference),
12-14 (Conference),
Aug. 20, Sept.
Aug. 24,
20, Nov.
Sept.12,
24,Dec.
Nov.10
12, Dec. 10
Anti-Aging/Cosmeceutical
Anti-Aging/Cosmeceutical
Event Event
Comprehensive
Comprehensive
Compounding
Compounding
Course (C
Course
3
) - Canada
(C3) - Canada
NEW! NEW! Date/Event/Location:
Date/Event/Location:
April 22-24/Anti-Aging/Cosmeceutical
April 22-24/Anti-Aging/Cosmeceutical
Hands-onHands-on
London, Ontario
London,• Four-day
Ontario • course
Four-day course Symposium/Houston,
Symposium/Houston,
Texas Texas
Dates: March
Dates:
8-11,
March
Mar.8-11,
29 – April
Mar. 29
1, June
– April7-10,
1, June
Sept.7-10,
13-16,
Sept. 13-16,
Nov. 15-18,
Nov.
Nov.
15-18,
29 – Nov.
Dec. 29
2 – Dec. 2 Autism Event
AutismNEW!
Event NEW!
Date/Time:Date/Time:
June 17/Autism
June 17/Autism
Webinar (7-8:30
WebinarPM(7-8:30
CST) PM CST)
PCCA International
PCCA International
Compounding
Compounding
Seminar Seminar
Date/Location:
Date/Location:
October 6-9/Houston,
October 6-9/Houston,
Texas Texas BHRT Events
BHRT Events
Dates/Event/Location:
Dates/Event/Location:
Feb. 11-13/BHRT/Infertility/Nutrition
Feb. 11-13/BHRT/Infertility/Nutrition
Symposium/Las
Symposium/Las
PCCA Worldwide
PCCA Worldwide
Networking
Networking
Retreat Retreat Vegas, Nev.;
Vegas,
MayNev.;
13-15/Practical
May 13-15/Practical
Approach Approach
to BHRT Symposium/Denver,
to BHRT Symposium/Denver,
Date/Location:
Date/Location:
July 9-10/Hawaii
July 9-10/Hawaii Colo.; Nov.
Colo.;
11-13/BHRT
Nov. 11-13/BHRT
Symposium/Charleston,
Symposium/Charleston,
S.C. S.C.
PCCA Canada
PCCA Regional
Canada Regional
SeminarsSeminars Dental Event
DentalNEW!
Event NEW!
Dates/Location:
Dates/Location:
Feb. 26-27/Calgary,
Feb. 26-27/Calgary,
Alberta; Nov.
Alberta;
5-6/Toronto,
Nov. 5-6/Toronto,
Ontario Ontario Date/Time:Date/Time:
Jan. 14/Dental
Jan. 14/Dental
Webinar (7-8:30
Webinar
PM(7-8:30
CST) PM CST)
CPM Services
CPM Services
Client Seminar
Client Seminar General Compounding
General Compounding
Events for
Events
Practitioners
for Practitioners
NEW! NEW!
Date/Location:
Date/Location:
October 6/Houston,
October 6/Houston,
Texas Texas Dates/Time:Dates/Time:
April 1/General
April 1/General
Compounding
Compounding
Webinar for
Webinar
Practitioners
for Practitioners
CPM Services
CPM Services
CoachingCoaching
Client Webinars
Client Webinars
(7 PM CST)
(7 PM CST) (7-8:30 PM(7-8:30
CST); PM
Sept.
CST);
16/General
Sept. 16/General
Compounding
Compounding
Webinar for Webinar for
Dates: Jan.
Dates:
26, Feb.
Jan.23,
26,March
Feb. 23,
30,March
April 27,
30,May
April25,
27,June
May29,
25, June 29, Practitioners
Practitioners
(7-8:30 PM(7-8:30
CST) PM CST)
July 27, Aug.
July31,
27,Sept.
Aug. 28,
31, Oct.
Sept.26,
28,Nov.
Oct.3026, Nov. 30 InfertilityInfertility
Event NEW!Event NEW!
CPM Services
CPM Services
FinancialFinancial
Management
Management
SeminarsSeminars Date/Location:
Date/Location:
Feb. 11-13/BHRT/Infertility/Nutrition
Feb. 11-13/BHRT/Infertility/Nutrition
Symposium/
Symposium/
Dates/Location:
Dates/Location:
Feb. 14/Las
Feb.
Vegas,
14/Las
Nev.;
Vegas,
MayNev.;
16/Denver,
May 16/Denver,
Colo.; Colo.; Las Vegas,
Las
Nev.
Vegas, Nev.
Nov. 14/Charleston,
Nov. 14/Charleston,
S.C. S.C. Marketing
Marketing
Event Event
IACP Compounders
IACP Compounders
on Capitol
onHill
Capitol Hill Date/Location:
Date/Location:
May 20-21/Marketing
May 20-21/Marketing
Symposium/Houston,
Symposium/Houston,
Texas Texas
Date/Location:
Date/Location:
June 19-22/Washington,
June 19-22/Washington,
D.C. D.C. Pain Management
Pain Management
Event Event
PCCA Advisory
PCCA Advisory
Council Meetings
Council Meetings Date/Location:
Date/Location:
Aug. 6-7/Pain
Aug.Management
6-7/Pain Management
Symposium/Seattle,
Symposium/Seattle,
Wash. Wash.
Dates/Location:
Dates/Location:
April 9-10/Kiawah
April 9-10/Kiawah
Island, S.C.;
Island,
Sept.S.C.;
10-11/Houston,
Sept. 10-11/Houston,
Texas Texas
PK Software
PK Software
Event Event
Pharmacy Pharmacy
Student Boot
StudentCamps
Boot Camps Date/Location:
Date/Location:
Aug. 12-14/PK
Aug. 12-14/PK
Software 2nd
Software
Annual
2nd
User
Annual
Conference/
User Conference/
Dates/Location:
Dates/Location:
Jan. 7-8/Houston,
Jan. 7-8/Houston,
Texas; MayTexas;
24-25/Houston, Texas; Texas; Houston, Texas
May 24-25/Houston, Houston, Texas
June 17-18/Houston,
June 17-18/Houston,
Texas; June
Texas;
28-29/London,
June 28-29/London,
Ontario; Aug.
Ontario;
9-10/Aug. 9-10/ Quality Assurance/Accreditation
Quality Assurance/Accreditation
Readiness
Readiness
Event NEW!
Event NEW!
Houston, Texas
Houston, Texas Date/Location:
Date/Location:
Aug. 30-31/Houston,
Aug. 30-31/Houston,
Texas Texas
Pharmacy
Pharmacy
Student Advanced
Student Advanced
Courses Courses Sports Medicine
Sports Medicine
Event NEW!
Event NEW!
Dates/Location:
Dates/Location:
July 26-27/Houston,
July 26-27/Houston,
Texas; JulyTexas;
29-30July
(Veterinary)/
29-30 (Veterinary)/ Date/Time:Date/Time:
March 25/Sports
March 25/Sports
Medicine Webinar
Medicine(7-8:30
WebinarPM(7-8:30
CST) PM CST)
Houston, Texas
Houston, Texas
Veterinary
Veterinary
Events Events
PCCA Institute
PCCA Institute
Online Courses
Online Courses Dates/Location/Time:
Dates/Location/Time:
March 4-6/Veterinary
March 4-6/Veterinary
Symposium/Parrot
Symposium/Parrot
Jungle Jungle
Date: March
Date:
22/Online
March 22/Online
Intro Veterinary
Intro Veterinary
Course Begins
Course Begins Island, Miami,
Island,
Fla.;
Miami,
Aug.Fla.;
26/Veterinary
Aug. 26/Veterinary
Webinar (7-8:30
Webinar
PM(7-8:30
CST); PM CST);
Register atRegister
Any Time
at Any
for the
Time
Following
for the Following
Self-StudySelf-Study
Online Course:
Online Course: Nov. 18/Veterinary
Nov. 18/Veterinary
Webinar (7-8:30
Webinar
PM(7-8:30
CST) PM CST)
AdvancedAdvanced
Pharmaceutical
Pharmaceutical
Care & Compounds
Care & Compounds
for Canines
for Canines
Wellness/Nutrition
Wellness/Nutrition
Events Events
PCCA Online
PCCAWebinars
Online Webinars
(7-8:30 PM
(7-8:30
CST)PM CST) Date/Event/Location:
Date/Event/Location:
Feb. 11-13/BHRT/Infertility/Nutrition
Feb. 11-13/BHRT/Infertility/Nutrition
Symposium/ Symposium/
Dates: Jan.
Dates:
14/Dental
Jan. 14/Dental
Webinar; March
Webinar;
25/Sports
March 25/Sports
Medicine Webinar;
Medicine Webinar; Las Vegas,Las Nev.;
Vegas,
AprilNev.;
29-May
April1/Wellness/Nutrition
29-May 1/Wellness/Nutrition
Symposium/Napa
Symposium/Napa
April 1/General
April 1/General
Compounding
Compounding
Webinar for
Webinar
Practitioners;
for Practitioners;
May 20/Men’s
May 20/Men’s Valley, Calif.
Valley, Calif.
Health Webinar;
Health June
Webinar;
17/Autism
June 17/Autism
Webinar; Aug.
Webinar;
26/Veterinary
Aug. 26/Veterinary
Webinar; Webinar;

For more
Forinformation
more information
call 800.331.2498
call 800.331.2498
or visitorwww.pccarx.com.
visit www.pccarx.com.
PCCA Members
PCCA Members
– go to–the
go to
Members-only
the Members-only
Web siteWebforsite
more
forinformation.
more information.
 Feature
Developing a Tretinoin Oral Liquid for
Patients Who Cannot Take Capsules
Linda F. McElhiney, PharmD, RPh,
FIACP, FASHP
Clarian Health Partners, Inc.
Indianapolis, Indiana
International Journal of Pharmaceutical Compounding
118 Vol. 14 No. 2 | March/April 2010
Bone marrow smear
from a patient with acute
promyelocytic leukemia
Abstract
Published information on alternative ways to administer commercial dosage
forms may not always be the best option for patients and the hospital
staff.There are resources available to research information about drugs and
excipients. A compounding pharmacist can review the information and,
based on training and experience in compounding, develop a formulation
to meet the individual needs of a patient. The tretinoin oral suspension
formulation included with this article is an example of how to develop
a formulation without a published stability study by utilizing various
compounding references and databases.
www.ijpc.com

T
Tretinoin (Vesanoid), commonly known as
Retin-A or Renova, is used topically for the
treatment of acne vulgaris or photodamaged
skin and palliation of fine wrinkles, mottled
hyperpigmentation, and tactile roughness of
facial skin as part of a comprehensive skin care
program. When taken orally, tretinoin is an
antineoplastic agent used alone or in combina-
tion with the following antineoplastic agents
for remission induction in acute promyelocytic
leukemia (APL):
• Arsenic trioxide
• Arsenic trioxide-gemtuzumab
• Daunorubicin
• Daunorubicin-cytarabine
• Idarubicin
Tretinoin is also being investigated for
post consolidation and maintenance therapy
in APL and for use in combination therapy
with arsenic trioxide for remission induction
in APL.
Tretinoin is only
commercially
available as a 10-mg
liquid-filled capsule.
It is a category X
drug and hazardous
precautions must be
used by the nursing
and medical staff
when administering
the drug.
Tretinoin is only commercially available as
a 10-mg liquid-filled capsule. It is a category
X drug and hazardous precautions must be
used by the nursing and medical staff when
administering the drug. Although this drug is
primarily administered to adult patients, not
all patients are able to swallow the capsules.
There are cases in institutional settings where
patients requiring tretinoin therapy cannot
take medications orally (NPO) because they
are intubated. These cases present a difficult
treatment challenge for the hematology/on-
cology staff.
www.ijpc.com
Feature
Table. Ingredients of Vesanoid (Tretinoin).
Name (Active Moiety) Type Strength
Tretinoin Active 10 milligrams in 1 capsule
(6%)
Beeswax Inactive N/A
Butylated hydroxyanisole Inactive N/A
Edetate disodium Inactive N/A
Hydrogenated soybean oil flakes Inactive N/A
Hydrogenated vegetable oils Inactive 18%
Soybean oil Inactive 70%
Gelatin Inactive N/A
Glycerin Inactive N/A
Yellow iron oxide Inactive N/A
Red iron oxide Inactive N/A
Titanium dioxide Inactive N/A
Methylparaben Inactive N/A
Propylparaben Inactive N/A
N/A = not applicable
}
COMPOUNDINGTODAY.COM
CompoundingToday.com is the heart of pharmaceutical
compounding information. This interactive website is a
vital resource for any practice setting that is preparing
individual medications
Subscribers Include:
• Hospitals
• Community
Pharmacies
• Home Health Care
Centers
• Compounding-Only
Pharmacies
• Infusion Centers
• Universities
• Vet Compounding
Pharmacies
Contact The International Journal
of Pharmaceutical Compounding
for Subscription Information:
405.330.0094 or 800.757.4572
www.CompoundingToday.com
dmehlhaff@ijpc.com
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 119
Feature

IJPC
Treatment Although the
Options manufacturer does
Although the
manufacturer does not recommend using
not recommend using
the contents of the
the contents of the
tretinoin capsules to tretinoin capsules to
extemporaneously
prepare a tretinoin oral extemporaneously
suspension, there are
limited case reports prepare a tretinoin oral
Each CD is a
Compounding Theme CDs

on altering the com-

suspension, there are
compilation of mercial dosage form
to treat NPO patients. limited case reports on
previously published In a patient with a
nasogastric (NG) tube, altering the commercial
IJPC articles and the tretinoin capsules
were cut open and the dosage form to treat
formulations in PDF contents were partially
NPO patients.
format. aspirated into a glass
syringe. The residual
contents of the capsule were mixed with soybean oil, aspirated into the
For a complete list of same syringe, and administered to the patient.1 Another reported option
was to mix the tretinoin capsules with sterile water, heat in a water bath
CD contents, see at 37°C to melt the capsules, and create an oily suspension for NG tube
administration.2 Tretinoin has also been administered sublingually by
www.ijpc.com/products

[ ]
Order one CD for $95.
Additional discount
with multiple cd orders.
(Plus shipping & handling)
For more information
contact IJPC Circulation at
800.757.4572 or email:
subs@ijpc.com
pricking the capsules with a needle and squeezing the capsule contents
beneath the patient’s tongue.3
None of these options are ideal for administration. There may be loss
of drug when aspirating or squeezing the contents of the capsules into
a syringe or when administering the drug sublingually. Tretinoin may
adhere to the container when melting the capsules in a water bath. The
loss could be significant and result in a subtherapeutic dose. Low plasma
levels have been reported when tretinoin has been administered through
a feeding tube, although patient-specific impaired absorption may have
been a factor.4
Another concern with these preparation and administration tech-
niques is that tretinoin is a hazardous drug. If the first two techniques are
not being done in a biological safety cabinet (BSC) or barrier isolator,
the person preparing the dose(s) may be unnecessarily exposed to the
hazardous drug. Equipment, such as the glass syringe or the water bath,
may also be contaminated. The sublingual administration technique is
exposing the person administering the tretinoin to a category X drug.
Many healthcare systems are implementing policies that restrict the ma-
nipulation of hazardous drugs to pharmacy personnel so that the dose(s)
can be prepared in a negative-pressure hazard room within a BSC or
barrier isolator.

INTERNATIONAL JOURNAL
Developing a Formulation for
PHARMACEUTICAL Tretinoin Oral Suspension
COMPOUNDING
After several failed and nominally successful attempts by the inpa-
tient pharmacy staff to prepare tretinoin doses for the intubated patients
in the intensive care units, a request was sent to the compounding phar-
macy to develop a tretinoin oral suspension. A search was done to find a

International Journal of Pharmaceutical Compounding www.ijpc.com

120 Vol. 14 No. 2 | March/April 2010

published stability study for an oral tretinoin
suspension, but there was no information avail-
able. Another search was done on the Internet
to find out the exact contents of the tretinoin
capsules. On the National Library of Medicine
website, all of the active and inactive ingredi-
ents were listed (see the accompanying Table).
Each ingredient was researched in Trissel’s
Stability of Compounded Formulations and the
databases on the International Journal of Phar-
maceutical, Inc.’s CompoundingToday.com
website to determine the chemical properties
and which ingredient and quantities should be
included in the new oral suspension formula-
tion. The following information summarizes
the results of the search.
Tretinoin, also known
as all-trans-retinoic
acid, is the most stable
in an oil base. It is
sensitive to heat, air,
and especially light.
Tretinoin
Tretinoin, also known as all-trans-retinoic
acid, is the most stable in an oil base. It is sen-
sitive to heat, air, and especially light. There
were several studies on topical formulations
containing water; however, there were no stud-
ies on nonaqueous vehicles. The tretinoin in
the vegetable-soybean oil vehicle in the com-
mercial capsules had a long shelf-life stability.
Based on stability indicating high-performance
liquid chromatography analysis, the time to
10% loss of tretinoin (t90) was calculated to be
453 days at 25°C, 678 days at 19°C, and 1289
days or 3.5 years frozen.
Butylated Hydroxyanisole
Butylated hydroxyanisole (BHA) is a
preservative and antioxidant used in con-
centrations of 0.005% to 0.02%. It is soluble
in oil. Antioxidants are used to minimize or
retard the oxidative processes that occur with
some drugs, such as tretinoin, and excipients,
such as oils, upon exposure to oxygen or in
the presence of free radicals. Oxidation causes
rancidity in oils.
www.ijpc.com
Feature
Edetate Disodium
Edetate disodium is an adjunct preserva-
tive and antioxidant used in concentrations of
0.02% to 0.1%. It is soluble in water.
Soybean Oil
Soybean oil is the refined fixed oil obtained
from the seed of the soy plant Glycine soja (Le-
guminosae). It occurs as a clear, pale yellow,
oily liquid with a characteristic odor and taste.
It may be used as an oleaginous vehicle and a
solvent in both topical and oral use prepara-
tions. It is commonly used as the fat source in
total parenteral nutrition. Silicone from plastic
syringes can be leached into the soybean oil.
•••••
The availability of all of the ingredients
chosen for the new formulation was also
researched. All of the ingredients are readily
}
COMPOUNDINGTODAY.COM
Featuring:
• Over 2,000 Formulations with
References and Documentation
• Physicochemical Database which
Interacts with each Formula
• USP <795> and USP <797>
Beyond-Use Dates
Contact The International Journal
of Pharmaceutical Compounding
for Subscription Information:
405.330.0094 or 800.757.4572
www.CompoundingToday.com
dmehlhaff@ijpc.com
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 121
Feature

Rx
available through most
chemical wholesal- Since tretinoin is
ers. An order for Tretinoin Oral Suspension
the ingredients not a category X drug, 10 mg/mL (Fixed Oil Base)
routinely stocked in
the compounding all weighing and For 100 mL
laboratory was placed
with one of the whole- compounding should Tretinoin 1 g
salers to be shipped Butylated hydroxyanisole 0.02 g
overnight. be done in a negative- Edetate disodium dehydrate 0.1 g
In the meantime, Soybean oil qs 100 mL
a formulation record pressure hazard
sheet was written and
is provided in this room within a BSC Note: All weighing and mixing of hazardous substances should be done in a
article. Since tretinoin protected environment, using antineoplastic precautions, as recommended by the
is a category X drug, or barrier isolator National Institute for Occupational Safety and Health,6 United States Phar-
all weighing and macopeial Convention7 standards, and the American Society of Health-System
compounding should using antineoplastic Pharmacists guidelines.8
be done in a negative-
pressure hazard room precautions. METHOD OF PREPARATION
within a BSC or 1. Calculate the required quantity of each ingredient for the total
barrier isolator using amount to be prepared.
antineoplastic precautions. To prevent contamination of the compound- 2. Weigh and/or measure each ingredient accurately.
ing equipment, disposable equipment should be used to prepare the 3. Add a portion of the soybean oil to the powders and mix well us-
suspension. A disposable mortar and pestle may be used to mix the pow- ing a disposable mortar and pestle or by the syringe method.
ders into the soybean oil and the final container, an amber glass bottle, 4. Add the mixture to a calibrated glass amber bottle and add soy-
can be calibrated to the desired volume so that the suspension can be bean oil to bring the mixture up to the desired volume.
brought to the desired amount with the soybean oil. The final mixture is 5. Cap and shake well to mix.
a smooth, yellow liquid that uniformly suspends upon shaking well. 6. Seal and label the bottle.
Another method that is good for mixing some hazardous drugs is the
syringe method. The powders can be weighed and backloaded into one PACKAGING
Luer Lock syringe, and the soybean oil can be drawn up into another Package in tight, light-resistant containers.6 Use glass bottles only.
Luer Lock syringe. The two syringes are connected with a Luer Lock-
to-Luer Lock connector and the contents mixed by pushing the contents LABELING
back and forth between the two syringes until a smooth, uniform suspen- Protect from light. Store at room temperature. Shake well. Antine-
sion is made. The mixture is then added to a clean, calibrated, glass oplastic agent—handle properly.
amber bottle, and soybean oil is added to the desired volume. Since the
mixing occurs over a short period of time, there is little concern about STABILITY
the silicone from the syringes leaching into the soybean oil. The syringes A beyond-use date of 6 months is appropriate for this preparation.6
and connector may be disposed in a hazardous waste container. Due to the nature of tretinoin and lack of stability studies, a conser-
Since no stability studies have been done on tretinoin oral suspen-
vative beyond-use date of 30 days is recommended.
sion, United States Pharmacopeial Convention standards should be used
to determine the beyond-use date. This formulation is a nonaqueous
liquid and a 6-month beyond-use date may be assigned. However, since
tretinoin is a hazardous drug and sensitive to light, heat and air, a con- within a BSC or barrier isolator by a trained pharmacy staff member.
servative beyond-use date of 30 days may be more appropriate to ensure The dose should be drawn up into an oral syringe, properly labeled, and
that the patient will be receiving an accurate dose for the prescribed put into a sealed baggie for delivery just prior to the scheduled adminis-
chemotherapy treatment. tration time. Although many facilities prepare patient-specific doses in
8 to 24 hour supplies, the tretinoin oral suspension dose should be pre-
pared just prior to the scheduled administration time since the soybean
Dispensing and Administering oil vehicle of the tretinoin suspension can leach the silicone from the
Tretinoin Oral Suspension plastic syringes.
The nursing and medical staff should be educated on the precautions
A bulk bottle of the tretinoin oral suspension should be prepared and that should be taken when administering the tretinoin oral suspen-
kept in the inpatient pharmacy. It should not be dispensed directly to the sion. Staff members should wear gloves, a gown, and mask to protect
patient unit. Since many healthcare systems are implementing policies themselves from exposure to the tretinoin. Pregnant staff members or
that restrict the manipulation of hazardous drugs to pharmacy person- members who are possibly pregnant should not handle tretinoin because
nel, the dose(s) should be prepared in a negative-pressure hazard room of its known teratogenic effects. The used oral syringe should be prop-

International Journal of Pharmaceutical Compounding www.ijpc.com

122 Vol. 14 No. 2 | March/April 2010
 Feature

erly disposed in a designated hazardous waste

container along with any other contaminated
equipment, such as gloves.
Conclusion
Published information on alternative ways
to administer commercial dosage forms may
not always be the best option for patients and
the hospital staff. There are resources avail-
able to research information about drugs and
excipients. A compounding pharmacist can
review the information and, based on training
and experience in compounding, develop a
formulation to meet the individual needs of a
patient. The tretinoin oral suspension formula-
tion included with this article is an example
of how to develop a formulation without a
published stability study by utilizing various
compounding references and databases.
References
A compounding pharmacist can review the
information and, based on training and experience
in compounding, develop a formulation to meet
the individual needs of a patient. The tretinoin oral
suspension formulation included with this article is
an example of how to develop a formulation without
a published stability study by utilizing various
compounding references and databases.
ville, MD: US Pharmacopeial Convention, Address correspondence to Linda F. McElhiney,
Inc.; 2005: 408–413. PharmD, RPh, FIACP, FASHP, Clarian Health
8. American Society of Health-System Partners, Inc., 550 N. University Boulevard, UH
Pharmacists. ASHP guidelines on handling 1451, Indianapolis, IN 43202. E-mail: lmcelhin@
hazardous drugs. Am J Health-Syst Pharm clarian.org
2006; 63: 1172–1193.

1. Shaw PJ, Atkins MC, Nath CE et al. ATRA

}
administration in the critically ill patient.
Leukemia 1995; 9(7): 1288.
2. Bargetzi MJ, Tichelli A, Gratwohl A et al.
Oral all-transretinoic acid administration
COMPOUNDINGTODAY.COM
in intubated patients with acute promyte-
Includes:
locytic leukemia. Schweiz Med Wochenschr
• Trissels’ 2 Clinical Pharmaceutical
1996; 126(45): 1944–1945.
Database
3. Kueh YK, Liew PP, Ho PC et al. Sublingual
• Standard Operating Procedures
administration of all-trans retinoic acid to a
• Discontinued Medication
comatose patient with acute promyelocytic
Database
leukemia. Ann Pharmacother 1999; 33(4):
• Bacterial Endotoxin Levels
503–505.
4. Takitani K, Kakao Y, Kosada Y et al. Low
• Base Salt Ester Weight
plasma levels of all-trans retinoic acid Conversions
after feeding tube administration for acute • Chemotherapy Vial
promyelocytic leukemia. AmJ Hematol 2004; Reconstitution and Stability
76(1): 97–98.
5. U.S. National Library of Medicine. Nation-
al Institutes of Health, Health & Human
Services. Daily Med. [Daily Med Website.]
Available at: http://dailymed.nlm.nih.gov/
dailymed/about.cfm. Accessed January 11,
2010.
6. National Institute for Occupational Safety
and Health. Preventing Occupational Exposure
to Antineoplastic and Other Hazardous Drugs in
Health Care Settings. NIOSH Alert. [NIOSH Contact The International Journal
Website.] Available at: www.cdc.gov/niosh/ of Pharmaceutical Compounding
for Subscription Information:
docs/2004-154/2004-165d.html. Accessed
405.330.0094 or 800.757.4572
April 24, 2007. www.CompoundingToday.com
7. United States Pharmacopeial Convention, dmehlhaff@ijpc.com
Inc. USP Pharmacists’ Pharmacopeia. Rock-

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 123
 Feature
Inventory Information Approval
System Certification and Flexible
Spending Account Purchases:
A New Year Brings Changes

Brandon Shuey, President & CEO

FlexTRAX Solutions
Wichita, Kansas

LaVonn A. Williams
International Journal of Pharmaceutical
Compounding
Edmond, Oklahoma

Abstract
There is no question that 2009 was a year of change within the pharmacy indus-
try. Several new requirements were implemented, including the need for an In-
ventory Information Approval System for accepting flexible spending or health
reimbursement account cards. Some pharmacies relied on the 90% exemption
rule, which is discussed within this article, or an alternative method to avoid the
expense of a point of sale. However, with flexible spending or health reimburse-
ment account card participation expected to reach 85% in 2010, now may be the
time for compounding pharmacists to weigh the pros and cons of Inventory In-
formation Approval System certification.
Inventory
Information
Approval System
The Inventory Information Approval
System (IIAS) was developed by an online
retailer (drugstore.com) in 2005. This is why
the terminology used by the Internal Revenue
Service (IRS) in its description of an IIAS
may seem unusual at first. For example, an
IIAS is described by the IRS as an “inventory
control” system tied to SKUs. The IIAS was
first introduced to brick-and-mortar retailing
by Walgreens in 2006. Walmart became the
first discounter with an IIAS in late 2006. After
these two retailers implemented IIAS technol-
ogy, it was generally easier to understand as a
point-of-sale system (POS) tied to UPC. By
the end of 2007, all online pharmacies that ac-
cepted flexible spending or health reimburse-
ment account (FSA/HRA) debit cards were
required to have an IIAS. By the end of 2008,
all chain pharmacies were required to have an
IIAS as well.1
An IIAS is similar to the system that has
been used by grocery stores ever since they
introduced the first barcode scanners in the
1970s to separate items eligible for purchase
under the Food Stamp Program from those

International Journal of Pharmaceutical Compounding www.ijpc.com

124 Vol. 14 No. 2 | March/April 2010
 Feature

Brief Facts About an Inventory Information

Approval System1
• Inventory Information Approval System (IIAS) technology was first used in
2005, but was not officially approved by the Internal Revenue Service (IRS) until
July 2006.
• To crack down on flexible spending or health reimbursement account (FSA/
HRA) providers that were not following prior IRS guidance on FSA debit cards,
the IRS decided that grocery and discount stores having in-store pharmacies
would not be allowed to accept FSA debit cards unless they installed an IIAS.
• The IRS permitted stand-alone chain or independent pharmacies (known as
“true pharmacies”) to accept FSA debit cards without an IIAS.
• After grocers and discounters challenged the IRS ruling, claiming that they and
their in-store pharmacies were being discriminated against, the IRS made two
changes in another ruling as of December 2006:
- Grocers and discounters were allowed to accept FSA debit cards until De-
cember 31, 2007 to give them sufficient time to install an IIAS.
- “True pharmacies” were required to install an IIAS after June 30, 2009, un-
less at least 90% of the individual pharmacy’s sales are of “FSA-eligible”
items (i.e., prescription drugs, over- the-counter items).
• By 2009, most grocers, discounters, and chain or Internet pharmacies in the
U.S. were required to have an IIAS in place in order to accept FSA debit cards.

that are not eligible. An IIAS works in much

the same way, but with medical FSAs/HRAs
instead of food stamps.1
The IRS implemented IIAS certification
in July 2009 to validate the eligibility of pur-
chases made with an FSA/HRA card. When
the regulation was announced, an organiza-
tion made up of a group of companies that
support health-card transactions, the Special
Interest Group for IIAS Standards (SIGIS),
was created to establish and maintain the list
of eligible items and manage IIAS certifica-
tion for pharmacies. IIAS certified systems
provide third parties with auto-substantiated
transaction data, which verifies the categories
of the items in the transaction at the time of
purchase. When transactions are received
from a non-IIAS system, the third party can-
not identify whether the purchased items are
prescriptions, over-the-counter medications,
or a noneligible item (e.g., a candy bar). These
nonauto-substantiated transactions require
paper-based validation by the third party after
the transaction has already been processed.
Auto-substantiated transactions require sub-
stantially less work for a third party to process
than a traditional transaction; therefore, it is
understandable that third parties may choose
to only accept transactions received from an
IIAS certified POS.

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 125
Feature

90% Exemption
Rule
Recognizing that eligible items make up
the majority of sales at many independent
pharmacies, the IRS approved an alternative
to IIAS certification—the 90% exemption
rule. Pharmacies whose sales are at least 90%
comprised of eligible items qualify for the
exemption, enabling them to transmit FSA/
HRA transactions without an IIAS system.
However, the 90% rule is optional for third
parties to support because the transactions
are not auto-substantiated. Some insurance
companies require that their participants only
use FSA/HRA cards at merchants on the IIAS
Merchant List published by SIGIS; transac-
Important Reasons to Promote Tax- tions transmitted from noncertified stores are
Favored Health Accounts rejected or declined. In fact, stores registered
under the 90% rule have reported consistent
• While other Internal Revenue Service (IRS)-approved “auto-adjudication” declines of FSA/HRA transactions, and many
systems for electronic substantiation of flexible spending accounts (FSA) have experienced an increase in card declines
debit card charges are geared towards health plan expenses, such as since the beginning of the year. Declined
copay matching or electronic transmittal of explanations of benefits, transactions have created embarrassing and
an Inventory Information Approval System (IIAS) is the only one that is frustrating situations for FSA/HRA custom-
designed for use with over-the-counter (OTC) and similar items, as well as ers, who are often forced to take their business
prescription drugs. to a certified competitor next door. Increased
• An IIAS is the first system with 100% “auto-adjudication” of an entire declines have also prompted many pharmacies
class of FSA debit card charges that has been widely adopted by the FSA to seek a compliant solution to ensure these
industry. A few FSA vendors had previously used proprietary systems transactions are accepted by the issuers.
which provided 100% auto-adjudication of prescription charges through
a pharmacy benefits manager, but they ran into numerous technical and
educational issues and were not adaptable to OTC.
• Some of the IRS rules on what OTC items are and aren’t eligible for FSAs
have proven rather arcane in practice; for example, condoms are eligible
since they prevent pregnancy, but products to lubricate them are not eli-
gible. An IIAS effectively manages this problem by verifying eligibility of
each OTC item at point-of-sale.
• Both paper claims and manual substantiation of FSA debit card charges
often required the submission of receipts with “full names” of OTC items;
but many stores abbreviate item names in such a way that it is almost
impossible to tell if the item is eligible. Also, most providers did not
reimburse sales tax on paper claims with “mixed” FSA/non-FSA receipts An Inventory Information Ap-
because they could not “split” the tax line item without being versed in proval System is technology
the sales tax laws of every state and locality in the U.S., a near impossibil- that is used by retailers to en-
ity. An IIAS avoids this by having the retailer itself verify item eligibility sure that all Flexible Spending
and “split” the sales tax.
• The process of demanding receipts or reimbursement for FSA debit card
Account/Health Reimburse-
charges that are not “auto-adjudicated,” known as “pay and chase” in the ment Account card transac-
industry (a term recognized by the IRS), proved particularly cumbersome tions are eligible expenses
for OTC items due to the lack of “auto-adjudication” systems and the high under Internal Revenue Ser-
potential for fraudulent or erroneous charges. An IIAS eliminates this by vice regulations. Every item in
providing an “auto-adjudication” system for OTC while preventing many
fraudulent or erroneous charges at retailers.
a store’s scanner database is
flagged “yes” or “no” for plan
Source: Wikipedia Website. December 22, 2009. http://wikipedia.org/wiki/Inventory_in- eligibility.1
formation_approval_system.

International Journal of Pharmaceutical Compounding www.ijpc.com

126 Vol. 14 No. 2 | March/April 2010

Point-of-Sale
System
If you are considering IIAS compliance, a
POS (the location where a transaction occurs)
system is your only solution. Entry POS sys-
tems that can provide IIAS compliance in addi-
tion to the fundamental features of a traditional
POS are available and affordable. The number
of FSA/HRA accounts has gradually increased
over the last several years, with record par-
ticipation expected in 2010. Plan participation
typically begins in January, and card holders
will begin using their FSA/HRA cards in the
first several months. Given the trends we have
seen over the last year, it is better to prepare
now than to disappoint your customers, or
worse, lose them to the competition.
Declined transactions have
created embarrassing and
frustrating situations for FSA/
HRA customers, who are
often forced to take their busi-
ness to a certified competitor
next door. Increased declines
have also prompted many
pharmacies to seek a compli-
ant solution to ensure these
transactions are accepted by
the issuers.
Conclusion
The development of the IIAS has elimi-
nated many of the problems that were involved
in using medical FSAs at retailers. Because
an industry-wide standard was nonexistent,
retailers had to develop their own procedures
to comply with the regulations set forth by the
IRS. This meant that many of the retailers had
to make separate contractual agreements with
www.ijpc.com
individual benefit administrators. However,
SIGIS, a group of companies who support
health-card transactions, created an industry
standard. An IIAS standard will give retailers
the chance to implement an industry-wide
solution, allowing acceptance of all healthcare
reimbursement cards at any participating loca-
tion. What this means to FSA debit card hold-
ers is that their eligible prescription and OTC
purchases will be automatically approved and
paid for through their reimbursement account
funds.1 With FSA/HRA card participation ex-
pected to reach 85% in 2010,3 now may be the
time for compounding pharmacists to weigh
the pros and cons of IIAS certification.
Although this article is presented for the benefit of
compounding pharmacists to keep them abreast of the
current technology available for the many compliance-
related requirements, a patient hand-out of frequently
asked questions about an FSA is included. One of the
goals of compounding pharmacy is to empower the pa-
tient to have more control over his medical well being.
YOUR QUALITY CONTROL LAB
When you think quality, think Eagle.
For more information, call 800.745.8916 • www.eagleanalytical.com
International Journal of Pharmaceutical Compounding
Feature
This goal can be met quicker by providing additional
information to the patient.
References
1. [No author listed.] Wikipedia. Inventory Approval
System. [Wikipedia Website.] December 22, 2009.
Available at: http://wikipedia.org/wiki/Inven-
tory_information_approval_system. Accessed
February 5, 2010.
2. [No author listed.] Fringe Benefits Management
Company. Frequently Asked Questions—Flexible
Spending Accounts. [FBMC Website.] Available at:
www.myfbmc.com/customers/faq_fsa.aspx. Ac-
cessed February 8, 2010.
3. Answers.com. Flexible Spending Account. [Answers.
com Website.] Available at: www.answers.com/
topic/flexible-spendingaccount. Accessed Febru-
ary 8, 2010.
Address correspondence to Brandon Shuey, President
& CEO, FlexTRAX Solutions, A KeyCentrix Com-
pany, 245 N. Waco, Suite 100, Wichita, KS 67202.
E-mail: bshuey@keycentrix.com
ne
On-Li ing
rt
Repo ble!
Avai a
l
Vol. 14 No. 2 | March/April 2010 127
PATIENT HANDOUT :: FLEXIBLE SPENDING ACCOUNTS
Frequently Asked Questions About Flexible
Spending Accounts2
Q: What is a Flexible Spending Account (FSA)?
A: An FSA is an Internal Revenue Service (IRS)-approved, tax-favored ac-
count that allows you to pay for eligible medical and/or dependent care
expenses. Each pay period, a portion of your pre-tax salary is deposited
into your FSA. You are then reimbursed from this account for your
eligible expenses. This allows you to save on income and Social Security
taxes.
Q: What are the eligibility guidelines for an FSA?
A: Your medical expense FSA may be used to reimburse eligible expenses
incurred by:
• Yourself
• Your spouse
• Your qualifying child
• Your qualifying relative
Additional qualifying criteria for a spouse, child, or relative may be
acquired from the IRS.
Q: What is the turnaround time for reimbursement request
processing?
A: The normal turnaround time for reimbursement requests processing is
five business days from the date a reimbursement request is received.
For more information, please refer to your benefit enrollment materials.
Q: What is needed for reimbursement?
A: The items needed in order to process a medical reimbursement request
are:
• A completed and signed reimbursement request form
• A copy of an explanation of benefits form, statement, bill, or receipt
showing the type of service, date of service, and amount of service
provided.
The items needed in order to process a dependent care reimbursement
request are:
• A completed and signed reimbursement request form
• A copy of a receipt, invoice, or bill from the provider showing the
name and address of the provider, the beginning and ending dates
of the provided services, the cost of the services, and the age, grade,
and name of the IRS-eligible dependent for whom the services were
provided.
Note: This information is general in nature. All responses may not apply to all FSAs. Patients are urged to refer to their plan documents and enrollment materials, or to contact their provider for
more details.
Q: Do I need to send original documentation with my
reimbursement request form?
A: No. Copies of statements, bills, or receipts are sufficient.
Q: Where can I obtain additional reimbursement request
forms?
A: Download forms by logging into your account; follow the prompts. You
may also call your provider to acquire additional forms either by fax or
mail.
Q: When can I start submitting requests for reimburse-
ments?
A: If you are an existing employee, requests for reimbursement can be
submitted after the start of your plan year. For example, if your plan year
starts on January 1, you can start sending charges incurred from that
date. Most FSAs are set up so that the entire amount you elect to have
deducted for the year is made available for use in the first day of the plan
year; you don’t have to wait for the cash to accumulate in your account.
However, if you are a new hire, you can submit requests incurred from
your effective date forward.
Q: What is the last day to submit reimbursement requests?
A: Most FSAs require that all requests for reimbursement must have
services incurred by the last date of your plan year. For example, if your
plan year is January 1 through December 31, all dates of service must be
incurred by December 31; however, most FSA plans have a “run-out” pe-
riod, giving you up to 90 days from the end of your plan year to submit
requests.
Q: Is there a mileage allowance for transportation to ob-
tain medical care?
A: Yes. As of January 1, 2010, the IRS has established the mileage rate as
$0.165 (16.5 cents) per mile. You also may seek reimbursement for park-
ing and toll fees incurred as a result of travel for your medical appoint-
ment.
Q: What type of documentation is required to obtain reim-
bursement for mileage, parking, and toll fees for doctor
visits?
A: A receipt, statement, or bill validating your doctor visit must be sub-
mitted with your mileage statement and your toll and/or parking fee
receipts.
Q: Is there a mileage allowance for transportation to and
from my local pharmacy?
A: Yes. A visit to your pharmacy for prescriptions will be treated as a visit to
your local healthcare provider.
Q: What is the standard manner in which to calculate
mileage for reimbursement?
A: Calculate the mileage on the actual bill/receipt detailing the following:
roundtrip mileage multiplied by the mileage rate for the time period of
the mileage. On the claim form, include the name of the provider visited.
Q: Can I have my reimbursements directly deposited to my
bank account?
A: Most FSA providers allow direct depositing, once the appropriate forms
are completed.
 Featuring...
Over 2,000 Updated
Formulations with References
and Documentation
Physicochemical Database
Interacts with each Formula
USP <795> and USP <797>
Beyond-Use Dates

Also Includes...
• Trissels’ 2 Clinical
To Use...
Pharmaceutics Database
• Go to www.CompoundingToday.com
• Standard Operating • Click on ‘Formulas’
Procedures • Go to ‘Formula Search’
• Discontinued Medication [Search by Dosage Form(s),
Database
• Bacterial Endotoxin
Component, or Use]
Levels
• Base Salt Ester Weight
Conversions
• Chemotherapy Vial
Yearly Subscriptions...
• Level 1: Access to Fifteen Databases: $200
Reconstitution and
Stability • Level 1 + Level 2: Access to Formulations
• Disinfectants Database and Standard Operating
• Filter Membrane Procedures: $495
Compatibility
• Level 1 + Level 2 + Level 3: Trissels’ 2
• Flavorings
• NaCl Equivalents Clinical Pharmaceutics Database: $995
• Vehicles
• Excipients Selection Aids
Contact IJPC for Subscription Information
405.330.0094 / 800.757.4572
www.CompoundingToday.com
dmehlhaff@ijpc.com

Brought to you by The International Journal of Pharmaceutical Compounding

3
SPECIAL
OFFERS
IJPC 1/2 OFF SALE
ANNUAL SETS
(2007, 2008, or 2009) with
binder $85 each
Valued at $170

BACK ISSUES
Purchase any ten issues
(your choice) for $125
For a list of journal topics visit:
www.ijpc.com/Backissues/
Valued at $250

IJPC BINdErS will be $10 each while supplies last. Each

binder holds up to two years of IJPC issues while providing
protection for your journals. Valued at $20

INTERNATIONAL JOURNAL

PHARMACEUTICAL To ordEr Call 800.757.4572 or 405.330.0094 ext.1

COMPOUNDING
 Feature

Commander John Burke

Warren County Drug Task Force

[ ]
Lebanon, Ohio

Abstract
Law enforcement and the military have long relied on canines to provide
protection of the handler and others involved in combating crime. One of
the extremely important uses of canines is in the detection of illegal drugs,
bombs, and other explosives to protect the President of the United States,
other dignitaries, and the general public. This article discusses the details
on a canine that was trained to detect major illicit pharmaceuticals.The ef-
forts of this program were made easier with the help of a compounding
pharmacist who willingly assisted the Warren County Drug Task Force in
the canine’s detection training by preparing and individually labeling cap-
sules that contained pure drug. Both parties share their experiences in this
important endeavor to combat the illegal distribution and transportation
of prescription drugs.

Commander Burke
also serves as
the president I have had a long and blessed career in law ment’s pharmaceutical diversion squad. For the
of the National enforcement. I spent the first 32 years with the past 10 years of my 42-year career, I have been
Association of
Drug Diversion Cincinnati Police Department; the last nine in charge of the Warren County Drug Task
Investigators. years, I formed and commanded the depart- Force located in southwest Ohio. We provide

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 131
Feature

drug enforcement for the entire county
of Warren, and assist all law enforcement
agencies that operate in Warren County and
Wilmington, Ohio. Additionally, we provide
training for law enforcement and educate
the general public on the abuse of both licit
and illicit drugs. An important tool in our
efforts to combat the illegal distribution and
transportation of prescription drugs is the
use of canines, which have been used by law
enforcement and the military to detect not
only drugs but bombs and other explosives.
Canines are also trained to locate and track
dead or live humans, as witnessed in both the
attack on the twin towers in New York and
the attack on the Alfred P. Murrah Federal
Building in Oklahoma City, Oklahoma.
Kilo, a black Labrador Retriever, is one of
the canines that we were able to acquire for
drug detection. Kilo is full of more energy
than a nine-year-old boy! He is trained on all
of the major illicit drugs, including heroin,
methamphetamine, and marijuana. Since all
of those drugs are inherently illegal to pos-
sess, Kilo can be used to obtain something
called probable cause. Probable cause is
sometimes difficult to define, but it is a legal
term that law enforcement and the courts
deal with on a daily basis. It is the basis for
police obtaining a search warrant, arresting
a suspect, and, in the case of a dog like Kilo,
being able to search, without a search war-
rant, a motor vehicle on the highway when
Kilo alerts.
The problem is that the drugs mentioned
above leave out a huge source of drug abuse
in this country and that, of course, is pharma-
ceuticals. Kilo could be trained on prescrip-
tion drugs, but then he would have no value
in providing his handler with probable cause
since there is no way to know if he is alerting
to the pharmaceuticals or the illicit drugs.
Since pharmaceuticals can very possibly be
legal, it destroys the use of the alert in court.
In the meantime, our drug task force, like
others across this nation, found ourselves
seeing massive amounts of prescription
drugs on our streets and being transported
on our highways. Thousands of dosage units
of oxycodone were being transported from
Broward County, Florida, to the Midwest.
No law enforcement canine in the country
to my knowledge was trained to detect these
and other common pharmaceuticals, allowing
traffickers to hide these drugs in their cars
without detection even if sniffed by police
canines. So for the past two years, I have
attempted to get approval and funding for a
second canine that could be trained for the
detection of the most abused prescription
drugs in the country. Thanks to a willing
new sheriff, Larry Sims, and a grant from a
pharmaceutical company, we were given our
chance.
As part of our endeavors to prevent the
illegal distribution and transportation of
prescription drugs, we decided to train Kash,
a Belgian Malinois, initially trained to detect
U.S. currency, to detect prescription drugs.

A Unique Opportunity for Compounding

Jeff Hill, RPh
Hill’s Compounding Pharmacy
Milford, Ohio

For quite some time, I have been aware of the efforts of the Warren County Drug Task force and of Commander John
Burke’s career and reputation regarding pharmaceutical diversion in southwest Ohio. Therefore, when Commander Burke
contacted me and explained the challenges in training Kash for the detection of major illicit pharmaceuticals, I was hon-
ored to be involved with the project.
Given the controlled status of the drugs involved, our first priority was given to confirming the proper licensing and the
procedures with our state board of pharmacy and with the Drug Enforcement Administration.
This was an unusual project for a pharmacist, as we are always concerned with making sure the ingredients are mea-
sured and weighed accurately. However, for this project the exact formulation for each drug was not significant since none
of the capsules would be ingested. More significant was the minimum number of grams contained in the total number of
capsules (i.e., from 3 to 5 grams of pure drug in 15 to 20 capsules, with no fillers) to give Kash a significant gram/sample
from which to train. Capsules were uniquely marked to identify one drug from another and were placed back inside their
respective original chemical jars with their original labeling intact for subsequent storage and future training. Empty cap-
sules were supplied to confirm that Kash was identifying the actual drug and not the gelatin capsules.
Over the years, we have compounded veterinary prescriptions for police canines for their own health needs. This was
a unique opportunity for our compounding pharmacy to be involved in a positive way with law enforcement from a new
perspective.

Address correspondence to Jeff Hill, RPh, Hill’s Compounding Pharmacy, 931 St. Route 28, Milford, OH 45150. E-mail: pharmacy@
hillscompounding.com

International Journal of Pharmaceutical Compounding www.ijpc.com

132 Vol. 14 No. 2 | March/April 2010
 Feature

The Belgian Malinois is a Belgian sheepherd- Conclusion

ing dog, sometimes mistaken for the German To our knowledge, Kash is the first police
Shepherd. Our dilemma was how to train this canine with the ability to detect and alert on
new dog for this new task since controlled prescription drugs. He is currently trained
substance pharmaceuticals available on the on hydrocodone, oxycodone, alprazolam,
retail market contained other ingredients diazepam, methadone, hydromorphone, and
such as acetaminophen, aspirin, ibuprofen, morphine. Additional prescription drug odors
and various binders and coloring agents. How can be introduced to Kash as warranted.
would the handler know if the dog was alert- I am very proud of this new canine and its
ing on the generic drug or on the substances handler, Deputy Brian Lewis from the Warren
that held the tablet together? County Sheriff’s Office. Lewis, Kash, and Kilo
Since I had a strong background in can be viewed on our website at www.wcdtf.
pharmaceutical diversion for many years, I org. I also want to thank Jeff Hill and Hill’s
was well aware of the fact that compounding Compounding Pharmacy for their willingness TOP: KASH
pharmacies exist around the country, and, to assist us in this important program. This bottom: kilo
conveniently, in my home state of Ohio. I canine would not be as well trained for his field
knew that these specialized pharmacies com- work without Jeff’s initiative and interest in our
monly worked with pure products that we project.
needed in order to make sure that Kash was
alerting on the controlled substance and not Address correspondence to Commander John Burke,
the other ingredients (excipients) in the pill, The Greater Warren County Drug Task Force, P.O.
tablet, or capsule. Box 898, Lebanon, OH 45036. E-mail: burke@
We quickly applied for and obtained our naddi.org
Drug Enforcement Administration license,
allowing us to purchase and handle all sched-
ules of controlled substances. I then went to
our local compounding apothecary, Hill’s
Compounding Pharmacy, in Milford, Ohio,
and met the owner and pharmacist, Jeff Hill. I
explained my dilemma to him, and his mind
immediately went to work and suggested
that we put the pure drug in capsules that
he would prepare and individually mark to
differentiate which controlled substance was
present.
Since there were no binders, coloring
agents, or additives, the handler would know
whether the dog was alerting on the actual
drug, or alerting on other additives. The
good news is that Kash was trained first on
commercially available pills and tablets, and
when the items produced by my compound-
ing pharmacist (Hill) were introduced, Kash
again identified them as he had the commer-
cial pharmaceuticals. Kash was also trained off
of the empty gelatin capsules just in case they
would have an influence.
Kash hit the streets in late December 2009
and now rides proudly with his friend Kilo in
the same police car. If needed, Kilo provides
probable cause and then Kash can also search.
However, the majority of our searches involve
search warrants where we already have prob-
able cause or consents to search. Therefore,
Kash will be used in the majority of searches
that we conduct.

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 133
 Feature
--------------
O w n i n g a n I n - N e t w o r k P h a r m a c y a n d a S e c o n d O u t- o f - N e t w o r k
P h a r m a c y t h at P e r f o r m s Co m po u n d i n g :
S uggestions on H ow to Avoid
B eing T erminated from the
P harmacy B enefits M anager N etwork
Jonathan E. Levitt, Esq.
Todd Mizeski, Esq.
Frier & Levitt, LLC
Pine Brook, New Jersey
The number of compounding pharmacies is on the rise because of
the profitability of compounded prescription reimbursement received
from cash paying customers. Often, a pharmacy will own two pharma-
cies, one in-network and a second out-of-network pharmacy to do the
compounding. This may lead to a battle with the Pharmacy Benefits
Manager (PBM). The out-of-network pharmacy can avoid the reduced
PBM reimbursement for compounding because the cash paying cus-
tomer will pay more than the PBM.
PBMs have addressed this issue by amending their agreements to re-
quire that pharmacies fill compounded prescriptions with the in-net-
work pharmacy when such pharmacy is “affiliated” with an out-of-net-
work compounding pharmacy. The term “affiliated” is rarely defined by
the PBM. Nevertheless, PBMs threaten the in-network pharmacy with
termination from the network if it refuses to fill compound prescriptions
at the in-network store. Obviously, the in-network reimbursement rate
for the compounded prescription barely compensates the pharmacy for
the cost of ingredients. Owning two pharmacies can be legitimate and
following basic ground rules may increase the chances of successfully
maintaining two stores.
If you are an in-network pharmacy owner that also happens to have
an ownership interest in an out-of-network compounding pharmacy,
International Journal of Pharmaceutical Compounding
134 Vol. 14 No. 2 | March/April 2010
proper planning may ensure that your in-network pharmacy is not
subject to termination from a PBM’s network. The key to successfully
defending against a PBM’s threat of termination is to demonstrate that
the two pharmacies are separate and distinct entities, each of which is
self-sufficient. There are several steps you can take to establish that the
two pharmacies are not affiliated, including:
• Give appropriate attention to corporate formation, such that there is
no legal relationship between the pharmacies (avoid parent/subsid-
iary relationship).
• Do not perform any compounding at the in-network pharmacy.
• Maintain separate business locations. If you cannot maintain separate
locations, establish separate entrances to the pharmacies and separate
work areas (e.g., walls separating the two pharmacies, separate coun-
ter space).
• Maintain separate infrastructure, including separate telephone num-
bers, facsimile numbers, websites, and e-mail addresses.
• Hire separate employees and maintain separate payroll.
• Keep separate corporate books, records, and meeting minutes.
• Maintain separate inventories and equipment.
• Establish separate tax identification numbers.
• File separate tax returns.
• Obtain separate Drug Enforcement Administration licenses.
This is not intended to be an exhaustive list. If your in-network phar-
macy is being threatened with termination from a PBM’s network, it is
our suggestion that you seek legal advice.
www.ijpc.com
 Compounding Theme

Each CD contains an
up-to-date collection
of full-text articles
published in IJPC
that are related to
the CD’s theme.

$95
each
Some of our Compounding CDs include:
• Bio-Identical Hormone Replacement Therapy Patients
• Cancer, AIDS, and Hospice Patients
• Dermatology and Wound Care Patients
• Pain Management Patients
• Veterinary Patients
• Implementing USP Chapter <797>
• Marketing, Legal, and Business Issues
• Peer-Reviewed Stability and Compatibility Studies

>> To order or for more information: Call 1.800.757.4572 or 405.330.0094 or visit: www.ijpc.com or www.CompoundingToday.com
 Quality Control
From Record Keeping to
Key Performance Indicators:
Managing Quality in Compounding Pharmacies
Gláucia Karime Braga, Doctor in Pharmaceutical Sciences
Maria José Vieira Fonseca, Doctor in Pharmaceutical Sciences
Faculty of Pharmaceutical Sciences of Ribeirão Preto
University of São Paulo
Ribeirão Preto, São Paulo, Brazil
ABSTRACT
Record keeping is fundamental in any quality-management system. Com-
pounding pharmacies use a quality-management system that is based
on the Good Compounding Practices, which emphasizes the necessity
and therefore the importance of maintaining records. However, the activ-
ity of recording without conducting further data analysis does not assure
continuous improvement of the preparations, services, and of the sys-
tem itself.The purpose of this article is to suggest some nonfinancial key
performance indicators that can be easily implemented by compound-
ing pharmacies to assist in the development of an organizational proce-
dure for measuring the quality of products and services.This is a new par-
adigm for managing quality in compounding pharmacies.
International Journal of Pharmaceutical Compounding
136 Vol. 14 No. 2 | March/April 2010
INTRODUCTION
For a quality-management system (QMS)
to be effective, it must include actions for plan-
ning, monitoring, measuring, and improving
quality procedures.1 Quality record keeping
is fundamental in any QMS, since the records
(1) provide objective evidence that the planned
actions were performed and (2) serve as the
framework for the development of monitoring
systems.
Compounding pharmacies follow the Good
Compounding Practices in the development
of a QMS.2,3 The records contained within the
system basically assume the role of providing
evidence, without further data handling. How-
ever, a compounding pharmacy’s QMS should
be documented, monitored, and reviewed in
order to be effective and achieve continuous
improvement of the pharmaceutical products
and services. For this reason, the processes car-
ried out in the pharmacy must be monitored,
measured, and analyzed.
Key performance indicators (KPI) can be
defined as variables that are representative of
processes. A KPI system allows for decisions
to be made based on information given by the
indicators. Indicators are useful for identifying
the following4:
• Conformance or not with the expectations
• Trends
• Opportunities for improvement
According to the International Conference
on Harmonization,5 performance indicators
should be identified and used to monitor the
effectiveness of processes within the quality
system. But, what should be measured? What
is the measurement procedure? How often
should measurements be performed? Where
is the source of information for measuring?
These are some of the concerns that com-
pounding pharmacists have when setting up a
QMS.
The purpose of this article is to suggest
some nonfinancial KPIs that can be easily
implemented by compounding pharmacies
to develop an organizational procedure for
measuring the quality of products and services;
a step beyond simply record keeping. This is
a new paradigm for managing quality in com-
pounding pharmacies.
Nonfinancial metrics are not generally per-
ceived as important tools for decision making,
business learning, and continuous improve-
ment. This article highlights the importance of
nonfinancial metrics. Since financial indicators
are critical to a business and presumably mea-
sured, this article does not address this topic.
www.ijpc.com

Suggested KPIs are listed below, with a brief
description of the important aspects of each
(summarized in the accompanying Table).
DEFINING PROCESSES
TO BE MEASURED AND
THE KEY PERFORMANCE
INDICATORS
Since the pharmacist in a pharmaceutical care
environment is responsible for patients under
their care, the new tasks of pharmacists, accord-
ing to the World Health Organization,6 can be
outlined as follows:
• Collaborating actively with physicians, regu-
latory authorities, and other health profes-
sionals, becoming a member of a multidisci-
plinary health care team
• Participating in public campaigns in order to
promote the rational use of medicines
• Promoting safe medication use in society
• Participating in research activities
• Engaging in interdisciplinary collaboration
• Counseling and providing information on the
medicines, ensuring patient´s understanding/
adherence to his/her treatment
• Advice on self-medication of the nonprescrip-
tion medicines
• Monitoring and detecting adverse drug reac-
tions (pharmacovigilance)
• Assessing the prescriptions, in order to see if
they are suitable and do not have incompat-
ibilities
• Managing the practice, recording, monitoring,
and reporting the outcomes of their practices
Because of these responsibilities, compound-
ing pharmacists have a tripartite relationship:
prescriber—medicine—patient. The processes
encompassing this relationship can be gathered
in three great groups, as outlined below:
1. Processes related to prescriber, such as
pharmaceutical assessment of prescriptions
2. Processes related to the obtainment of a
compounded medicine, such as purchasing,
compounding, training of personnel, auditing
3. Processes related to the patient, such as
dispensing
Processes Related to Prescriber:
Pharmaceutical Assessment of
Prescriptions
The pharmacist/prescriber relationship
is guided by the prescription and the out-
comes of its pharmaceutical assessment. This
process is important to evaluate the plausibil-
www.ijpc.com
Quality Control
ity of the prescription regarding dosage form, deviation found in each material. It is possible
drugs, dose, duration of treatment, and drug to track the supplier of the material. This
interaction and compatibility, in order to avoid information is important feedback about the
problems. We suggest the following KPIs for quality of purchased materials and call for
this process: actions of these suppliers. If the dialogue
between the supplier and the compounding
• Number and types of prescription errors:
pharmacy was not possible or if the material
- How many erroneous prescriptions were
presented to the pharmacy?
supplied was frequently out of specifications,
the pharmacist can decide to discontinue
- What types of errors were found?
purchasing from this supplier.
- Were the errors most frequently related
to drug dose, route of administration,
physical-chemical, or pharmacological
incompatibilities?
- Were there any trends on prescribing?
This indicator answers these questions
and shows trends in prescriptions. With this
information, the compounding pharmacist
can develop health educational programs for
prescribers, which can improve the quality of
prescriptions.
• Number and types of pharmaceutical
interventions that have a positive influence
on treatment:
- How many interventions did the com-
pounding pharmacist make in a month?
- What types of interventions were made?
- To what classes of drugs were the inter-
ventions most frequently related?
Compounding
According to Ide and colleagues,7 this indi-
Obviously, compounding is the core process
cator can improve the quality of pharmacists
of compounding pharmacies, and, unfortu-
since a good value of this indicator can moti-
nately, deviations may affect the quality of
vate the pharmacists to enroll in continuous
preparations. For this reason, the process must
education programs and make more positive
be closely monitored and measured. We sug-
interventions.
gest the following indicators:
Processes Related to the Compounding
of a Prescription First Pass Approval: This indicator measures
Purchasing, compounding, training of the number of compounded preparations
personnel, and auditing are the main processes that were dispensed without re-analysis or
related to compounding a prescription. The rework. With this indicator, we can determine
following indicators can be used to measure how many deviations were found in a month
and how many reworks or re-analyses was
the effectiveness of these processes.
carried out. We can also determine what types
of deviations were found. This information
Purchasing
can provide compounding pharmacists with
For regulatory reasons, compounding
ideas to improve the performance of this core
pharmacies must select suppliers that have the
process.
ability to supply raw materials and package
materials according to applicable specifica-
tions. Moreover, these suppliers must be Complaint: “Complaint is defined as a state-
ment that something is wrong or not good
enrolled in a qualification program.2,3 The sug-
enough.”8 Patients may complain about the
gested indicator for this process is as follows:
quality of compounded preparations and the
Purchasing Loss of Quality: This KPI measures services provided by the pharmacists, such as
the number of materials that were rejected dispensing. This KPI measures the percent-
in quality-control tests. The pharmacist can age of complaints per number of compounded
“open this indicator” and analyze the type of preparations that were dispensed. It is
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 137
Quality Control
important to highlight that complaints are
an indicator of a patient’s perception of the
quality of compounded preparations and/or
pharmaceutical services. However, the absence
of complaints is not an indicator of a patient’s
satisfaction.
Training of Personnel
Training is one of the main control mea-
sures that can be used to minimize sanitary
risks in compounding.9 However, it is impor-
tant to assure that all efforts addressed to train-
ing are taken into effect. More than training
and recording it, assessing the effectiveness of
training is vital to keeping the processes within
the QMS under control. For this reason, we
suggest the following KPI:
Training Quality: This is an indicator that
measures effective training. Obviously, this
indicator would also provide the compound-
ing pharmacist with the number of trainings
that were not effective. The pharmacist can
investigate the reasons these trainings were not
effective and develop corrective actions that
can range from teaching strategies to changing
the trainers.
Auditing
Auditing is a systematic, independent, and
documented process used to acquire evidence
of compliance to established requirements. We
suggest the following KPI:
Regulatory Compliance: This is an indicator
that measures the percentage of regulatory
requirements of Good Compounding Practices
that “were” fulfilled per the number of total
requirements of Good Compliance Practices
that “should be” fulfilled. It is also important to
know which requirements were not met in or-
der to discuss the reasons why and to develop a
corrective action plan.
Processes Related to the Patient
The paradigm of the doctor as a prescriber
and the pharmacist as a dispenser are progres-
sively being broken, and the pharmacist is tak-
ing more responsibility for the drug therapy,
especially the outcomes of dispensing.6 Coun-
seling, including providing information on the
medicines to ensure that a patient understands
and adheres to his/her treatment, is one of the
responsibilities of the compounding pharma-
cist in a pharmaceutical care environment. For
this reason, we suggest the following KPI:
Patient Compliance: This indicator (1) mea-
sures the percentage of patients that comply
International Journal of Pharmaceutical Compounding
138 Vol. 14 No. 2 | March/April 2010
with the dosage instructions for compounded
preparations and (2) measures the pharma-
ceutical counseling. This indicator provides
a good opportunity to improve the quality of
information provided on the labeling of com-
pounding preparations and the information
provided during consultations, and to encour-
age the patient to take more responsibility
regarding his/her treatment.
Key Performance
Indicator Reports
and Decision-making
Process
KPIs do not decide anything. The com-
pounding pharmacist must analyze the infor-
mation given by the indicators and must make
decisions based on the information obtained.
In order to make the KPI analysis easier,
KPI reports must be elaborated. Graphic
methods of displaying data are encouraged
and are important adjuncts to data analysis and
presentation. Bar charts are very simple but
effective visual data displays. Pareto analysis is
a good statistical tool to choose the issues that
will have to be treated first because of their
high incidence and impact.8,10
KPI reports are a valuable high-level map
of performance of the processes carried out
by the compounding pharmacies, and, for
this reason, it is strongly advised that the KPI
reports be available for regulatory agency
inspectors upon request, mainly during Good
Compounding Practices inspections.
CONCLUSION
Organizations regularly measure their
finances, but seldom measure their processes.
Record keeping, which is emphasized by the
Good Compounding Practices as necessary
and important, is essential for an effective
QMS. However, documentation is not enough
if there is no data handling, since the presence
of records does not assure continuous improve-
ment of the products, services, and, finally, the
QMS. In this article, the authors have suggested
some KPIs that are simple to calculate and that
can be readily implemented in compounding
pharmacies.
It is important to highlight that an indicator
per se does not decide anything. The pharmacist
in charge is responsible for making decisions
based on the information shown by the indicator.
The nonfinancial KPIs proposed in this
article are important tools for decision making,
business learning, and continuous improve-
ment. For this reason, the indicators bring to the
organizations a new challenge; the challenge of
measurement-based decisions.
REFERENCES
1. Associação Brasileira de Normas Técnicas.
ABNT Number ISO 9001: Sistema de Gestão da
Qualidade—Requisitos 2008.
2. Agência Nacional de Vigilância Sanitária.
Regulamento Técnico sobre Boas Práticas
de Manipulação de Medicamentos para Uso
Humano em Farmácias. Resolução RDC Reso-
lution 67 of October 8, 2007. Diário Oficial da
União, Poder Executivo, Brasília, DF, 2009 de outubro
de 2007, Seção I. [Agencia Nacional de Vigilancia
Sanitaria Website.] Available at: www.anvisa.gov.
br. Accessed December 15, 2009.
3. United States Pharmacopeial Convention, Inc.
United States Pharmacopeia 30/National Formulary
25. Rockville, MD: US Pharmacopeial Conven-
tion, Inc.; 2006: 511–514.
4. Attadia LC, Martins RA. Measurement of
performance as a basis for evolution of continu-
ous improvement: A study theoretical. Revista
Produção 2003; 13(2): 33–41.
5. [No author listed.] U.S. Department of Health
& Human Services. U.S. Food and Drug
Administration. International Conference on
Harmonization. International Conference on Har-
monization – Draft Guidance: Q10 Pharmaceutical
Quality System. [U.S. Food and Drug Administra-
tion Website.] May 26, 2009. Available at: www.
fda.gov/RegulatoryInformation/Guidances/
ucm128030.htm. Accessed December 15, 2009.
6. Everard M, Gous AG, Mackie CA et al. Develop-
ing Pharmacy Practice: A Focus on Patient Care.
World Health Organization Headquarters in
Geneva; 2006: 1–97.
7. Ide N, Gotou S, Mori M. Proposal for a new
tool to evaluate clinical pharmacy practice
based on the percentage of pharmaceutical
interventions that influence medical treatments.
Yakugaku Zasshi 2008; 28(8): 1215–1220.
8. Braga GK. Complaint handling in pharmaceuti-
cal companies. Quality Assurance Journal 2007;
11(1): 16–21.
9. Braga G K. Tese de Doutorado apresentada ao
Departamento de Ciências Farmacêuticas, Fac-
uldade de Ciências Farmacêuticas de Ribeirão
Preto, Universidade de São Paulo, Ribeirão
Preto. Identificação dos Riscos Sanitários na Ma-
nipulação de Medicamentos Alopáticos Não Estéreis em
Farmácia Comunitária o Papel das Boas Práticas de
Manipulação No Controle Desses Riscos; 2009.
10. Bolton S. Pharmaceutical Statistics: Practical and
Clinical Applications. 3rd ed. New York, NY:
Marcel Dekker, Inc.; 1997: 1–646.
Address correspondence to Gláucia Karime Braga,
Doctor in Pharmaceutical Sciences, Rua Cila 2500
ap 31 Ed. Marianas, 15015-800 São José do Rio
Preto, São Paulo, Brazil. E-mail: glauciakbraga@
yahoo.com.br
www.ijpc.com

Table. Suggested Key Performance Indicators for Compounding Pharmacies.
KPI NAME OBJECTIVE
Prescription-
related Process
Prescription Error Measuring the percentage
of prescriptions that show
errors and analyze what
kind of errors the pharma-
cists are handling
Pharmaceutical Measuring the percent-
Intervention age of pharmaceutical
interventions that had a
positive impact on treat-
ment and review the types
of interventions made, if
they were before or during
the treatment
Compounding-
related Process
Purchasing loss of Measuring the percentage
quality of materials that failed in-
spection, the type of mate-
rial, and the deviation, and
documenting the supplier
from which the materials
were purchased
First Pass Approval Measuring the percentage
of compounded prepara-
tions that were dispensed
without re-analysis and/or
rework
Complaints Measuring the percentage
of complaints about com-
pounded preparations
Training Quality Measuring the percent-
age of trainings that were
considered effective
Regulatory Measuring the percentage
Compliance of regulatory requirements
of Good Compound-
ing Practices that were
fulfilled against total
requirements
Patient-related
Process
Patient Compliance Measuring the percentage
of patients that followed
dosage instructions on
the labels of compounded
preparations and as
instructed during patient
consultations
www.ijpc.com
Quality Control
SOURCE OF
EQUATION FREQUENCY INFORMATION
Prescription error = (number of Monthly Pharmaceutical assess-
prescriptions with error/number of ment of prescription
prescriptions) × 100 records
Pharmaceutical intervention = [(num- Monthly • Pharmaceutical
ber of pharmaceutical interventions assessment of
that optimized the treatment + number prescription records
of pharmaceutical interventions that • Pharmaceutical care
avoided problems)/number of pharma- records
ceutical interventions] × 100
Purchasing loss of quality = (number of Monthly • Raw material quality-
purchased material that failed inspec- control records
tion /number of purchased material) × • Packaging material
100 quality-control
records
First pass approval = (number of Monthly • Compounding
compounded products – [number of re- records
worked products + number of products • End-product quality-
with reanalysis]/number of compounded control records
products) × 100
Customer Complaints = (number of Monthly Complaint records
complaints/number of dispensed com-
pounded medicines) × 100
Training quality = (number of trainings Quarterly Training records
considered effective/number of train-
ings) × 100
Regulatory compliance = (Number of Annually Audit records
requirements of Good Compounding
Practices that were fulfilled/number of
requirements) × 100
Patient compliance = (number of pa- Quarterly Pharmaceutical care
tients that followed dosage instructions records
on the labels of compounded prepara-
tions and as instructed during patient
consultations/number of patients that
used compounded medicines) × 100
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 139
 Calculations
Shelly J. Stockton, BS Pharm, PhD, RPh
College of Pharmacy
Southwestern Oklahoma State University
Weatherford, Oklahoma
1
A formula for testosterone nasal spray is as follows:1
Testosterone 1g
Alcohol 10 mL
Propylene glycol 20 mL
Benzalkonium chloride 15 mg
Purified water qs 100 mL
A. How much of each ingredient would be needed to fill
twelve 15-mL nasal spray bottles?
12 bottles × 15 mL/bottle = 180 mL
Formula conversion factor = 180 mL/100 mL = 1.8
Testosterone: 1 g × 1.8 = 1.8 g
Alcohol: 10 mL × 1.8 = 18 mL
Propylene glycol: 20 mL × 1.8 = 36 mL
Benzalkonium chloride: 15 mg × 1.8 = 27 mg
Purified water: qs 180 mL
B. The benzalkonium chloride is available as a 1:750 w/v stock solu-
tion. How much would be needed for the amount deter-
mined in part A above?
27 mg × 1 g/1000 mg × 750 mL/1 g = 20.25 mL
C. What is the percent strength of propylene glycol in this
formula?
20 mL propylene glycol/100 mL formula × 100 = 20% v/v
D. The specific gravity of propylene glycol is 1.038. How many
grams would be needed to prepare the formula in part A?
36 mL × 1.038 g/mL = 37.37 g
E. If the propylene glycol is found to be contaminated with
1.7 ppm of arsenic, how much arsenic would be contained
in each bottle of the nasal spray?
36 mL p.g./12 bottles = 3 mL propylene glycol/bottle
3 mL p.g./bottle × 1.7 g arsenic/1 × 106 mL p.g. × 1 × 106 mcg/g
= 5.1 mcg arsenic/bottle
F. If the pharmacist mistakenly weighs 2.13 g of testosterone
to prepare the formula in part A, what is the percent error
in the measurement?
Error = 2.13 g - 1.8 g = 0.33 g
% error = 0.33 g/1.8 g × 100 = 18.33%
International Journal of Pharmaceutical Compounding
140 Vol. 14 No. 2 | March/April 2010
2
The normal blood level of testosterone in males is 270 to 1070
ng/dL.2 If a 5-mL blood sample is found to contain 32.6 ng of
testosterone, does this patient’s testosterone level fall within
the normal range?
32.6 ng/5 mL × 1000 mL/L × 1 L/10 dL = 652 ng/dL
Yes, this patient’s testosterone level of 652 ng/dL falls within the
normal range.
3
A pharmacist needs to weigh 32 mg of dehydroepiandroster-
one (DHEA) in order to prepare a compound. He has in the
pharmacy a balance with a sensitivity of 4.5 mg and needs to
weigh this quantity with a minimum of 5% accuracy.
A. What is the minimum weighable amount for his balance?
4.5 mg × 100%/5% = 90 mg
B. How can the 32-mg quantity of DHEA be weighed using the
aliquot method and starch as the diluent?
32 mg × 5 = 160 mg of DHEA
90 mg aliquot × 5 = 450 mg dilution
450 mg - 160 mg = 290 mg starch
1. Weigh 160 mg of DHEA and 290 mg of starch.
2. Mix thoroughly.
3. Weigh a 90-mg aliquot from this mixture, which will contain
32 mg of drug.
Double-check:
160 mg DHEA + 290 mg starch = 450 mg mixture
160 mg DHEA/450 mg mixture x 90 mg mixture = 32 mg DHEA
4
The information for Testopel (testosterone implantable pellets)
states that two 75-mg pellets should be implanted for each 25
mg of testosterone propionate required weekly.3 However, tes-
tosterone propionate has been discontinued, and testosterone
cypionate is administered by injection every two weeks.
A. If this same dose information can be applied for testoster-
one cypionate, how many 75-mg pellets would be required
for a patient receiving a 75-mg injection of testosterone
cypionate every two weeks?
75 mg/2 weeks = 37.5 mg/week
37.5 mg/week × 2 pellets/25 mg/week = 3 pellets
B. The Testopel information also states that approximately 1/3 of the
material is absorbed in the first month, 1/4 in the second month,
and 1/6 in the third month.3 Based on this information, how
much testosterone would be absorbed from the above dose
during each of the first three months after implantation,
and how much testosterone would be remaining after the
third month?
3 pellets × 75 mg/pellet = 225 mg
www.ijpc.com
 Calculations

flavor?
First month: 1/3 × 225 mg = 75 mg absorbed
Second month: 1/4 × 225 mg = 56.25 mg absorbed
Third month: 1/6 × 225 mg = 37.5 mg absorbed
What’s your
Total absorbed = 168.75 mg
Amount remaining = 225 mg - 168.75 mg = 56.25 mg remaining

References
1. Allen LV Jr. Testosterone 1-mg/0.1-mL nasal spray. IJPC 2000; 4(6):
462.
2. Wickersham RM, Novak KK, eds. Normal Laboratory Values. Facts
& Comparisons 4.0 [book online]. St. Louis, MO: Facts and Compari-
sons; 2009.
3. Wickersham RM, Novak KK, eds. Testopel. Facts & Comparisons 4.0
[book online]. St. Louis, MO: Facts and Comparisons; 2009.

Address correspondence to Shelly J. Stockton, BS Pharm, PhD, RPh, College

of Pharmacy, Southwestern Oklahoma State University, 100 Campus Drive,
Weatherford, OK 73096.

Whatever your flavor is, Spectrum’s flavors are

guaranteed to satisfy. Our flavors are made from
the finest ingredients and are so delicious that
taking medicine is an easier and tastier experience
even for the most fussy patients.

800.791.3210
SpectrumRx.com

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 141
 Basics of Compounding
Loyd V. Allen, Jr., PhD, RPh
International Journal of Pharmaceutical Compounding
Edmond, Oklahoma

Claudia C. Okeke, PhD, RPh

Claumek PharmaScience
Rockville, Maryland

Considerations for Implementing United States Pharmacopeia Chapter <797>

Pharmaceutical Compounding—Sterile Preparations,
Part 18: Verification of Automated
Compounding Devices for Parenteral
Nutrition Compounding and Finished
Preparation Release Checks and Tests
Abstract
A sound quality-assurance program, which should include standard operating procedures,
documentation, verification, and analytical and microbiological testing, is necessary to ensure
the quality of compounded preparations. This article discusses in a practical matter verifica-
tion of automated compounding devices for parenteral nutrition compounding and finished
preparation release checks and tests, and provides practice clarification to the standards set
forth by the United States Pharmacopeial Convention, Inc.

International Journal of Pharmaceutical Compounding www.ijpc.com

142 Vol. 14 No. 2 | March/April 2010
 Basics

This article represents the 18th
in a series of articles pertaining to
the implementation of United States
Pharmacopeia Chapter <797>
Pharmaceutical Compounding—
Sterile Preparations.
A quality-assurance (QA) program is a
system of written procedures and scien-
tific measurements designed to ensure the
maintenance of proper, accurate, and safe
compounded preparations. The need for a QC
system is well documented in the United States
Pharmacopeia (USP) chapters for compounded
preparations.1 A QA program for compound-
ing should include at least the following eight
separate but integrated components:
1. Training
2. Standard operating procedures (SOP)
3. Documentation
4. Verification
5. Testing
6. Cleaning and disinfecting
7. Containers, packaging, repackaging, and
storage
8. Outsourcing
tions for sterility and endotoxins and the out-
side laboratory testing of preparations to verify
strength, purity, and other parameters.
Quality I mprovement
Quality improvement (QI) is an ongoing
effort to improve preparations, services, or
processes. These efforts can seek incremen-
tal improvement over time or breakthrough
improvement all at once. QI activities in the
pharmacy can include identifying the cause
of failure when a preparation fails a QC test,
developing and implementing methods to
prevent the failure, and continued testing to
verify whether the improvements eliminate the
problem.
Quality Related Event
Quality related events (QRE) involve the
incorrect compounding and/or dispensing
of a medication that is received by a patient,
including a variation from the prescriber’s
prescription order. Included activities are:
• Clinical abuse/misuse
• Dispensing an incorrect drug, incorrect
drug strength, incorrect dosage form, or
drug to the wrong patient; mislabeled and/
or incorrectly compounded preparation
• Drug-allergy interactions
• Drug-disease contraindications
• Drug-drug interactions
• Failure to identify and manage over-utiliza-
tion
• Incorrect drug dosage or duration of drug
treatment
• Providing inadequate or incorrect packag-
ing, labeling, or directions
• Significant or unexpected reaction of a
patient to a compounded preparation
• Therapeutic duplication
Training
Personnel involved in nonsterile or sterile
compounding require additional, specific
training and periodic retraining beyond the

The first four components are discussed in

this article, however, before getting into specif-
ics, some definitions that are key components
in a discussion of quality issues are provided.

Definitions
Quality Assurance
QA is the planned and systematic activities
implemented in a quality system so that qual-
ity requirements for the pharmacy’s prepara-
tions or services are fulfilled. QA activities
involve processes in the pharmacy setting
and include training staff to assure proper
operation of equipment, developing master
formulation records to assure standardized
compounds, and using and verifying com-
pounding process records to assure that each
batch is made correctly and consistently.

Quality Control
Quality control (QC) involves the observa-
tion techniques and activities used to fulfill re-
quirements of quality. Pharmacy QC examples
can include the sampling of sterile prepara-

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 143
Basics

• Personnel cleanliness and garb

• Purchasing
• QA
• Safety
• Shipping
• Testing
• Training and retraining

SOPs were discussed in a previous article within this series2; there-

fore, an in-depth discussion on SOPs is not included in this article.

Documentation
The purpose of documentation is to provide a permanent record
of all aspects of compounding operations and procedures that are
described in USP Chapters <795> and <797>. Information on the
compounding record should be entered as the tasks are performed.
Additionally, beyond-use dating and sterility studies, where appropri-
ate, should be documented by reference to:

1. Stability studies published in peer-reviewed literature

2. In-house or laboratory-conducted stability and/or sterility studies
3. National compendia
4. Extrapolation of above based on professional judgment

training needed for routine dispensing duties. A thorough QA program
for compounded preparations requires documentation of both training
and skill competency. Personnel training for sterile preparation com-
pounding should meet or exceed the standards set forth in United States
Pharmacopeia (USP) Chapter<797>. Numerous techniques and technolo-
gies can be used for training, including seminars, audiovisual instruction,
college classes, etc.
Standard Operating
Procedures
SOPs for pharmaceutical compounding are documents that describe
how to perform routine and expected tasks in the compounding envi-
ronment, including but not limited to procedures involving:
Verification
Verification involves authoritatively signed assurance and
documentation that a process, procedure, or piece of equipment is
functioning properly and producing the expected results. The act of
verification of a compounding procedure involves checking to ensure
the calculations, weighing and measuring, order of mixing, and com-
pounding techniques and equipment were appropriate and accurately
used. The quality of ingredients should be verified upon receipt and
again prior to each use. Verification may require outside laboratory
testing when in-house capabilities are not adequate. Equipment veri-
fication methods are sometimes available from manufacturers of the
specific equipment or can be developed in house. The responsibility
for assuring that equipment performance is verified, including work
completed by contractors, resides with the compounder. The com-
pounding facilities and equipment should be of appropriate capacity
and should be designed for the compounding being performed.

• Beyond-use dating
• Chemical and physical stability Verification of Automated
•
•
Cleaning and disinfecting
Compounding methods
Compounding Devices for
• Dispensing Parenteral Nutrition
• Environmental quality and maintenance
• Equipment maintenance, calibration, and operation Compounding
• Formulation development Speed, efficiency, and accuracy are reasons for using automated
• Labeling compounding devices (ACDs) in hospitals and other healthcare
• Materials and final compounded preparation handling and storage settings. Parenteral nutrition (PN) compounding, a labor-intensive
• Measuring and weighing process, can provide many opportunities for errors either in calcula-
• Packaging and repackaging tions, preparation, or checking. PN solutions may have up to 20 or
• Patient monitoring, complaints, and adverse event reporting 30 ingredients ranging from micrograms to grams. Improved accu-
• Patient or caregiver education and training racy and precision, as well as efficiency and speed, are advantageous

International Journal of Pharmaceutical Compounding www.ijpc.com

144 Vol. 14 No. 2 | March/April 2010
 Basics

but can only be achieved if the devices are verified to be working

correctly.
Accuracy
The simplest method of checking the accuracy of an ACD is to use
water as a solution and program it to deliver replicates of different
volumes of the water. The water can then be weighed (taring for the
container) to confirm delivery of the proper quantity. For example, if
the ACD is programmed to deliver 25 mL of water, the weight of that
quantity should be 25 g.
Another method is to pump replicate volumes of a single electro-
lyte solution and have them analyzed for the electrolyte. The analyst
can establish a standard curve using the solution that is pumped and
compare it to the pumped volumes.
Regardless of which method is used, the ACD must perform within
the specifications provided by the manufacturer before the ACD is
used in the compounding of sterile preparations.
Precision
The results of the accuracy testing, if done in replicates, and
compared on a daily record will provide information on the precision
of the ACD as it relates to the day-to-day variations in performance
of the ACD.
Finished Preparation Release
Checks and Tests
Inspection of Solution Dosage
Forms and Review of Compounding
Procedures
A QA program must involve the final inspection of the compounded
preparation as well as a review of the records/documentation of the
ingredients and procedures used in its preparation.
Physical I nspection
To ensure consistency, each unit in a batch should have a uniform
weight or volume within a narrow range. Dosage units are defined as
dosage forms containing a single dose or a part of a dose in each unit.
If multidose units are compounded in a batch formulation, the total
number of units should not deviate from ± 10% of the theoretical
number of units.
Weight and volume assessment can be done by visual inspection.
Care should be taken to preserve the integrity of each preparation dur-
ing the assessment procedures. It can be assumed that the concentration
is uniform throughout the preparation and between containers of the
same preparation.

15-Minute Endotoxin Testing

The Endosafe®-PTS™ rapid test system is an accepted and
beneficial alternative to traditional LAL for in-process testing
and end-product release.
• FDA-licensed cartridges pre-loaded with all test components
• No preparation of standards required
• Results in 15 minutes
• Simple, one-button operation
• Detects .005-10 EU/mL
• Portable, handheld system
The PTS™ provides faster results for improved process efficiency
and ease-of-use over traditional methods while offering the additional
benefits of portability, improved accuracy and reproducibility.
For more information, call us at 1.877.CRIVER.1 or visit us at
www.criver.com/pts.

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 145
Basics
Additional QA checks should include a visual inspection for foreign
materials and expected appearance, as well as a measurement of pH,
as applicable. Additional information on finished preparation release
checks and tests involving physical inspection can be reviewed in an
earlier article within this series.3
Compounding Accuracy C hecks
A QA program for compounded preparations should include test-
ing during the compounding process and of the finished compounded
preparation, when appropriate, as described in USP Chapters <795>
and <797>. A more detailed presentation can be found in USP Chapter
<1163>, an informational chapter. The compounder should have a basic
understanding of pharmaceutical analysis to ensure that valid results
are obtained when tests are being conducted, whether they are done in
house or outsourced. Testing every compounded preparation is neither
practical nor officially required, but compounders should conduct visual
inspections and know the following:
1. The importance of testing in the overall quality program in the com-
pounding facility
2. When to test
3. What to test
4. What method(s) to use
5. How to interpret the results
6. The limits of the test
7. Specific actions required when a preparation does not meet
specifications
Additional information on finished preparation release checks and
tests involving compounding accuracy checks can be reviewed in an
earlier article within this series.3
Investigative and corrective action should extend to other prepara-
tions that may have been associated with the specific failure or discrep-
ancy. Testing may involve one, or more than one, quality attributes, and
each test will have one or more acceptable procedures, usually with
well-defined acceptance criteria.
The goal in testing is to determine accurately the adequacy of the
compounding process and the quality of the preparation. Any testing
procedure used should have accuracy, speed, reproducibility, and speci-
ficity. No single testing procedure is suitable for all drugs or prepara-
tions because a number of factors determine the validity and reliability
of results.
Compounding professionals have two options for the testing that
is required for compounded preparations or its ingredients. Some
testing methods can be performed easily at the compounding site, but
some may need to be outsourced to a contract laboratory. Some testing
methods can be conducted in house with proper training and a modest
investment in instrumentation, including, but not limited to:
• Weight and volumetric measurements
• pH
• Density
• Refractive index
• Endotoxins
• Sterility
• Ultraviolet and visible spectroscopy
International Journal of Pharmaceutical Compounding
146 Vol. 14 No. 2 | March/April 2010
If testing is done at the site of compounding, appropriate equip-
ment shall be obtained and qualified either by the manufacturer or by
the compound professional upon purchase and shall be maintained,
calibrated, and used properly. If testing is outsourced, the compounding
professional should determine what to outsource, how to select a labora-
tory, and should develop an ongoing relationship with the laboratories
chosen. Contract laboratories shall follow standards set forth in USP
general chapters, as appropriate, and preferably should be registered
with the U.S. Food and Drug Administration (FDA).
Selection of a Testing Method
One general consideration in the selection of a testing procedure is
the type of information needed, such as quantitative (strength, con-
centration), semiquantitative (where a tolerance level is involved, as in
endotoxin levels), or qualitative (presence/absence testing, including
substance identification, sterility). Another consideration involves the
physical and chemical characteristics of the analyte, including solubility,
partition coefficient, dissociation constant (pKa), volatility, binding, and
the quantity present. The testing method selected also depends upon
factors such as sample handling/preparation/purification requirements,
type of data needed, and levels of specificity and accuracy required.
(See the accompanying Table for suggested testing methods for different
dosage forms.)
Pharmaceutical analysis decisions include procedure selection,
administrative factors, obtaining a representative sample (the num-
ber of preparation units selected to adequately represent the entire
formulation (e.g., 10 randomly selected capsules from a preparation of
100 capsules), and storage/shipping of the sample, sample preparation
for analysis, the actual analysis, data acquisition, data treatment, and
interpretation.
The compounding facility is responsible for implementing a program
using selected testing methods for the preparations compounded in the
facility. Examples of general and microbiological testing methods are
discussed later in this article. Selected testing methods for bulk sub-
stances and various dosage forms, which are described in USP Chapter
<1151>,1 are also shown in the accompanying Table.
Sampling Requirements
Before collecting samples for testing, compounding professionals
should consider:
• The quantity of preparation being compounded
• A specific prescription versus batch compounding
• The number of samples needed
• Whether it will be destructive or nondestructive testing
• Appropriate methods of obtaining representative samples
• Physical state of the samples (solid, liquid, gas)
• Type of container required for collection and storage
• Any special handling and shipping requirements or restrictions (e.g.,
controlled drug substances, dangerous or hazardous chemicals, flam-
mable or caustic substances, refrigerated or frozen preparations)
Storage Requirements
Storage requirements for samples must be specified, including type of
container, temperature, humidity, and light.
www.ijpc.com
Basics

Table. Selected Compendial Testing Methods for Bulk Substances and Various Dosage Forms.1
Bulk Sub-stances and Testing Method
Dosage Forms Wt Vol pH Osm RI Sp Gr MP UV/Vis HPLC GC IR Ste-rile Endo-toxin PM
Bulk Substances – – + – + – + + + + + – +a –
Injections + + + + + + – + + + – + + +
Irrigations + + + + + + – + + + – + + –
Ophthalmics + + + + + + – + + + – + – +b
Sterile Implant Gels + + + + + + – + + + – + + –
Sterile Implant Solids + + – – – – + + + + – + + –
aEndotoxin testing may be needed for bulk substances used in compounding some sterile preparations.
bSolutions only, not suspensions or ointments

+ = test applicable PM = particulate matter

– = test not applicable RI = refractive index
GC = gas chromatography Sp Gr = specific gravity
HPLC = high-performance liquid chromatography UV/Vis = ultraviolet/visible spectroscopy
IR = infrared spectroscopy Vol = volume
MP = melting point Wt = weight
Osm = osmolality/osmolarity

VERIFICATION OF AUTOMATED COMPOUNDING DEVICES (ACDs) FOR PARENTERAL NUTRITION

COMPOUNDING
• Accuracy
• Precision
Item Requirements Yes No Comment/SOP
Accuracy
Are ACDs used?
Is the ACD tested for volume and weight? Volume ____ ____
Weight ____ ____
Is a detailed SOP used for testing the ACD?
Is a detailed SOP used to document
procedures to follow if the ACD is out of
specifications?
Are specific gravities of ingredients used ____ ____
in the ACD?
If specific gravities are used, is a detailed
SOP available on how to determine
specific gravity in the event an ingredient
does not have it listed in its package
information? ____ ____
Are tolerances well defined for the ACD?
Is the final volume checked and compared
to theoretical volume?
Is periodical chemical testing done for
quality assurance?
Precision
Are daily records maintained on
performance characteristics of the ACD?
Are the daily records evaluated regularly
to confirm the performance of the ACD?
Are ingredients with narrow therapeutic
indices (e.g., KCl) closely monitored?

SOP = standard operating procedure

International Journal of Pharmaceutical Compounding www.ijpc.com

148 Vol. 14 No. 2 | March/April 2010
 Basics

Sample and procedures are explained in USP Chapter

Interference
The effect(s) that any substance has on
the preparation that may interfere or alter
the results must be known beforehand. When
sending a preparation to a contract laboratory,
the compounder should provide the complete
formulation so that the laboratory can quickly
determine if any interfering substances are
present.
Data
Interpretation
Requirements
The collection of raw data from the test-
ing process must be completed accurately.
One must ensure that appropriate and valid
descriptive statistics (e.g., mean, standard
deviation) are used to analyze the data and
that the operating parameters of the analyti-
cal instruments are well established. Refer-
ence values, if available, should be provided
with the analytical results. A description of
the analytical controls used by the labora-
tory is important for documentation, as is the
source of reference standards used to establish
standard curves.
<71>. Bacterial endotoxin (pyrogen) testing
ing United States Pharmacopeia Chapter
<797> Pharmaceutical Compounding—
can be conducted using commercial kits or by Sterile Preparations, part 16: Suggested
purchasing the components separately. Endo- standard operating procedures. IJPC 2009;
toxin testing may be performed in house with 13(6): 546–553.
appropriate training and experience. Details 3. Allen LV Jr, Okeke CC. Basics of com-
on bacterial endotoxin testing are found in pounding: Considerations for implement-
USP Chapter <85>. ing United States Pharmacopeia Chapter
<797> Pharmaceutical Compounding—
Sterile Preparations, part 8: Stability
Summary and beyond-use dating. IJPC 2008; 12(4):
A sound QA program includes detailed 344–353.
SOPs, documentation, verification, and ana-
lytical and microbiological testing as appro-
priate to particular compounded preparations. Address correspondence to Loyd V. Allen, Jr., PhD,
Compounding professionals are to decide on RPh, International Journal of Pharmaceutical
the types of testing and degree of testing that
will be a part of their QA program. They also
Compounding, 122 North Bryant Avenue, Edmond,
OK 73034: E-mail: lallen@ijpc.com
must decide whether to do testing in house
or outsource it to a contract laboratory. A QA
program is necessary to ensure the quality of
compounded preparations.
References
1. United States Pharmacopeial Convention,
Inc. USP Pharmacists’ Pharmacopeia. Rock-
ville, MD: US Pharmacopeial Convention,
Inc.; 2008: 779, 793, 923–934.
2. Okeke CC, Allen LV Jr. Basics of com-
pounding: Considerations for implement-

Personnel
Requirements and
Considerations
If testing is done in house, personnel
involved in this activity must be appropriately
trained and evaluated with documentation of
the training and evaluation. If testing is out-
sourced, the compounder must be assured of
the credentials, proper training, and continu-
ing competency activities of the personnel in
the contract laboratory. It is preferable that
the contract laboratory be registered with the
FDA.

Sterility Testing
Microbiological testing for pharmacy
compounding includes sterility, endotoxin,
preservative effectiveness testing, and micro-
bial limit testing, as detailed in USP Chapter
<797>. Sterility tests can be conducted using
commercial kits or by developing and verify-
ing USP sterility testing protocols. Standards

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 149
 Formulations
Acyclovir 5% in Oral Adhesive Paste
Rx
For 100 g
Acyclovir 5 g
Mineral oil, Light qs
Oral Adhesive Paste 95 g
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Add a few drops of light mineral oil to the acyclovir powder and
mix to form a smooth paste.
4. Incorporate the Oral Adhesive Paste geometrically and mix until
uniform.
5. Package and label.
PACKAGING
Package in tight, light-resistant containers.1
LABELING
Keep out of reach of children. Use only as directed.
STABILITY
A beyond-use date of up to 6 months can be used for this preparation.1
USE
Acyclovir in an oral adhesive paste has been used in the treatment of
cold sores (herpes labialis) and mucutaneous herpes simplex virus. A
finger cot or glove should be used during application to prevent the oc-
currence of autoinoculation of other sites and transmission of the virus
to others.2
QUALITY CONTROL
Quality-control assessment can include theoretical weight compared
to actual weight, pH, specific gravity, active drug assay, color, texture-
surface, texture-spatula spread, appearance, feel, rheological properties,
and physical observations.3
DISCUSSION
Acyclovir is a synthetic purine nucleoside analog antiviral agent that
is derived from guanine. It is active against Herpesviridae, including
herpes simplex virus types 1 and 2. A commercial cream is available
for the treatment around the mouth of perioral herpes, cold sores, and
fever blisters. This preparation can be used for those that extend into the
mucosal area. A commercial oral adhesive paste (Orabase Plain) can be
used, or the Oral Adhesive Paste can be prepared. (See formula on page
159 for Oral Adhesive Paste).
Acyclovir (C8H11N5O3, MW 225.20) is a synthetic purine nucleoside
analog used as an antiviral agent. It is used in the treatment of genital
herpes, herpes zoster, and varicella in immunocompetent individuals. It
occurs as a white to off-white crystalline powder that is slightly soluble
in water and insoluble in alcohol. It melts at temperatures above 250ºC
International Journal of Pharmaceutical Compounding
150 Vol. 14 No. 2 | March/April 2010
with decomposition. It should be preserved in tight containers. The
injection has a pH between 11.0 and 12.5. It is commercially available as
capsules, tablets, and a suspension; acyclovir sodium is available as the
injection form.1,2
Light mineral oil is a transparent, colorless, viscous liquid that is practi-
cally tasteless and odorless when cold; when warm, it has a faint odor.
It is used as an emollient, solvent, lubricant, therapeutic agent, and ole-
aginous vehicle. It has a specific gravity of 0.818 to 0.880. It is insoluble
in water or alcohol. It is miscible with volatile and fixed oils, with the
exception of castor oil. To promote miscibility/solubilization, a small
amount of a suitable surfactant can be added. When exposed to heat and
light, it undergoes oxidation with the formation of peroxides and ulti-
mately involving an autocatalytic process. Stabilizers, such as butylated
hydroxyanisole, butylated hydroxytoluene, and alpha-tocopherol can be
used as antioxidants to retard the oxidative process. Mineral oil can be
sterilized by dry heat and should be stored in an airtight container, pro-
tected from light in a cool place. It is incompatible with strong oxidizing
agents.4
Oral Adhesive Paste is composed of gelatin, pectin, xanthan gum,
sodium carboxymethylcellulose (medium viscosity), polyethylene oxide
(WSR-301), and Plasticized Hydrocarbon Gel.5 Plasticized Hydrocarbon
Gel contains light and heavy mineral oil, polyethylene glycol 1450, and
methylcellulose (4000 cps). It is a non-water-soluble gel that adheres
to mucosal surfaces and body tissues upon application and is used to
provide protection of tissue and for the delivery of pharmaceuticals
to the site of application. Orabase Plain is a mixture of gelatin, pectin,
sodium carboxymethylcellulose in hydrocarbon gel with polyethylene,
and mineral oil.
References
1. United States Pharmacopeial Convention, Inc. USP Pharmacists’
Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention,
Inc.; 2008: 775–779, 1421.
2. McEvoy GK, ed. AHFS Drug Information–2008. Bethesda, MD: Ameri-
can Society of Health-System Pharmacists; 2008: 3506–3508.
3. Allen LV Jr. Standard operating procedure for performing physi-
cal quality assessment of ointments/creams/gels. IJPC 1998; 2(4):
308–309.
4. Sheng JJ. Light mineral oil. In: Rowe RC, Sheskey PJ, Quinn ME, eds.
Handbook of Pharmaceutical Excipients. 6th ed. London, UK: Pharmaceu-
tical Press; 2009: 447–449.
5. Allen LV Jr. Oral adhesive paste. IJPC 2010; 14(2): 159.
www.ijpc.com

Acyclovir 200-mg/5-mL Oral Suspension (From the Injection)
Rx
For 100 mL
Acyclovir sodium 4 g
Ora Plus 50 mL
Ora Sweet or Ora Sweet SF qs 100 mL
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Reconstitute the acyclovir sodium vial with the smallest quantity
of purified water required to allow withdrawal from the vial.
Note: It does not have to all be in solution.
4. Place in a suitable calibrated container.
5. Add the Ora-Plus geometrically and mix well.
6. Add sufficient Ora-Sweet or Ora-Sweet SF to volume and mix
well.
7. Package and label.
PACKAGING
Package in tight, light-resistant containers.1
LABELING
Keep out of reach of children. Use only as directed. Shake Well.
STABILITY
A beyond-use date of 12 hours can be used for this preparation.1
USE
Acyclovir oral suspension is used in the treatment of genital herpes,
herpes zoster, and varicella in immunocompetent individuals.2
QUALITY CONTROL
Quality-control assessment can include weight/volume, pH, specific
gravity, active drug assay, color, rheological properties/pourability,
physical observation, and physical stability (discoloration, foreign mate-
rials, gas formation, mold growth).3
DISCUSSION
Occasionally, acyclovir suspension may be in short supply, and this can
be easily addressed by compounding pharmacists using the capsules to
prepare an oral suspension. However, when the capsules are also in short
supply, there may be an occasion when another drug source is required,
which could be the injection. Normally, acyclovir injection would not
be used for oral administration but in the event it is required, the above
formulation can be used. One should be cognizant of the short beyond-
use time, which is based upon the injection.
Acyclovir (C8H11N5O3, MW 225.20) is a synthetic purine nucleoside
analog used as an antiviral agent. It is used in the treatment of genital
herpes, herpes zoster, and varicella in immunocompetent individuals. It
occurs as a white to off-white crystalline powder that is slightly soluble
www.ijpc.com
Formulations
in water and insoluble in alcohol. It melts at temperatures above 250ºC
with decomposition. It should be preserved in tight containers. The
injection has a pH between 11.0 and 12.5. In this formula, the vehicles
are buffered, which will serve to lower the pH of the final preparation;
it will also result in much of the acyclovir coming out of solution and
form a suspension.
Acyclovir is commercially available as capsules, tablets, and a suspen-
sion; acyclovir sodium is available as the injection form. Acyclovir
suspension contains acyclovir 200 mg/5 mL, and methylparaben,
propylparaben, carboxymethylcellulose sodium, flavor, glycerin, micro-
crystalline cellulose, and sorbitol.1,2
Ora-Plus is an oral suspending vehicle that accepts dilution of up to
50% or more with water, flavoring agents, or syrups and still retains
its suspending properties. It has a pH of approximately 4.2 and an
osmolality of about 230 mOsm/kg. It is a thixotropic vehicle with a
viscosity of approximately 1000 cps at 25ºC. It contains purified water,
microcrystalline cellulose, sodium carboxymethylcellulose, xanthan
gum, carrageenan, sodium phosphate, and citric acid as buffering
agents; simethicone as an antifoaming agent; and potassium sorbate and
methylparaben as preservatives.4
Ora-Sweet syrup vehicle is a flavoring vehicle for oral extemporaneous
preparations. It is flavored with a citrus-berry flavor blend and contains
glycerin and sorbitol to prevent "cap-lock," a problem associated with
many syrups. It is buffered to a pH of approximately 4.2 and has an
osmolality of about 3240 mOsm/kg. It contains purified water, sucrose,
glycerin, sorbitol (5%), flavoring, sodium phosphate, and citric acid as
buffering agents, and potassium sorbate and methylparaben as preserva-
tives.4
Ora-Sweet SF sugar-free syrup is a flavoring vehicle for oral extem-
poraneous preparations. It is a sugar-free, alcohol-free syrup flavored
with a citrus-berry flavor blend. It is buffered to a pH of approximately
4.2 and may be used alone or in combination with other vehicles. It will
tolerate a dilution to 50% with dissolved actives in water or suspending
agents and still retain an acceptable taste. It has an osmolality of 2150
mOsm/kg. It contains water, sodium saccharin, xanthan gum, glycerin,
sorbitol, citric acid, and sodium citrate as buffers; methylparaben,
propylparaben, and potassium sorbate as preservatives; and flavoring
agents.4
References
1. United States Pharmacopeial Convention, Inc. USP Pharmacists’
Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention,
Inc.; 2008: 775–779, 1421.
2. McEvoy GK, ed. AHFS Drug Information–2008. Bethesda, MD:
American Society of Health-System Pharmacists; 2008: 790–800,
3506–3508.
3. Allen LV Jr. Standard operating procedure for quality assessment of
oral and topical liquids. IJPC 1999; 3(2): 146–147.
4. Ora-Plus; Ora-Sweet; Ora-Sweet SF. [product information]. Min-
neapolis, MN: Paddock Laboratories, Inc.
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 151
Formulations

Ciclopirox 10% in Isopropyl Alcohol Nail Solution

not to be taken orally. Isopropyl alcohol boils at 82.4ºC and has a specific

Rx gravity of 0.786. It is miscible with chloroform, ethanol, glycerin, and

For 100 mL
Ciclopirox 10 g
Isopropyl alcohol (99%) qs 100 mL
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Dissolve the ciclopirox in sufficient isopropyl alcohol to volume.
4. Package in 10-mL dropper bottles.
5. Label.
PACKAGING
Package in tight, light-resistant containers.1
LABELING
Keep out of reach of children. Use only as directed.
water; soluble in acetone and insoluble in salt solutions. It should be
stored in a cool place. Isopropyl alcohol is listed as incompatible with
oxidizing agents (hydrogen peroxide, nitric acid), and it may be salted
out from aqueous mixtures by the addition of sodium chloride, sodium
sulfate, or other salts, as well as by sodium hydroxide.4
References
1. United States Pharmacopeial Convention, Inc. USP Pharmacists’
Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention,
Inc.; 2008: 127, 775–779, 1431
2. Allen LV Jr. Standard operating procedure for quality assessment of
oral and topical liquids. IJPC 1999; 3(2): 146–147.
3. McEvoy Gk. AHFS Drug Information–2008. Bethesda, MD: American
Society of Health-System Pharmacists; 2008: 3539–3542.
4. McCoy CP. Isopropyl alcohol. In: Rowe RC, Sheskey PJ, Quinn ME,
eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC:
American Pharmaceutical Association; 2009: 346–348.

STABILITY
A beyond-use date of up to 6 months can be used for this preparation.1

USE
Ciclopirox topical nail solution is used in the treatment of onychomy-
cosis.

QUALITY CONTROL
Quality-control assessment can include weight/volume, pH, specific
gravity, active drug assay, color, clarity, rheological properties/pour-
ability, physical observation, and physical stability (discoloration, foreign
materials, gas formation, mold growth).2

DISCUSSION
Ciclopirox (C12H17NO2, MW 207.27) occurs as a white to slightly
yellowish-white crystalline powder. It is slightly soluble in water and
freely soluble in ethanol.1 Ciclopirox appears to exert its antifungal
effect by causing intracellular depletion of essential substrates and/or
ions; however, the exact mechanism is unknown. Ciclopirox is available
as the base and as the olamine. The ciclopirox olamine is available in a
cream or lotion form. Ciclopirox is available as a gel, shampoo, and as a
solution (nail lacquer). The advantage to the nail lacquer is it retains the
ciclopirox at the site of application for a long period of time. The dis-
advantage is that it is sometimes difficult to remove as the film-forming
residue can build up unless removed thoroughly. The solution presented
here can be applied daily, and the solution can be thickened if desired by
adding a small amount of hydroxyethylcellulose or other alcohol-soluble
thickening agent.3

Isopropyl alcohol (C3H8O, MW 60.10, isopropanol) is a clear, colorless,

mobile, volatile flammable liquid with a characteristic odor resembling a
mixture of ethanol and acetone and a bitter taste. It is used in cosmetics
and pharmaceuticals primarily as a solvent in topical applications and is

International Journal of Pharmaceutical Compounding www.ijpc.com

152 Vol. 14 No. 2 | March/April 2010

Clotrimazole 1% Oral Adhesive Paste
Rx
For 100 g
Clotrimazole 1 g
Mineral oil, light qs
Oral Adhesive Paste 99 g
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Add a few drops of light mineral oil to the clotrimazole powder
to form a smooth paste.
4. Incorporate the clotrimazole mixture geometrically into the Oral
Adhesive Paste and mix until uniform.
5. Package and label.
PACKAGING
Package in tight, light-resistant containers.1
LABELING
Keep out of reach of children. Use only as directed.
STABILITY
A beyond-use date of up to 6 months can be used for this preparation.1
USE
Clotrimazole oral adhesive paste has been used in the treatment of ap-
propriate oropharyngeal candidiasis areas.2
QUALITY CONTROL
Quality-control assessment can include theoretical weight compared
to actual weight, pH, specific gravity, active drug assay, color, texture-
surface, texture-spatula spread, appearance, feel, rheological properties,
and physical observations.3
DISCUSSION
Clotrimazole (C22H17ClN2, MW 344.84) is an imidazole derivative,
a synthetic azole antifungal agent. It occurs as a white to pale yellow
crystalline powder that melts at about 142ºC, with decomposition. It
is practically insoluble in water and freely soluble in alcohol. It is used
orally in the form of a lozenge and topically as a cream, lotion, or solu-
tion. This adhesive paste may be appropriate for some lesions where the
paste can be applied. To achieve maximum benefit of the lozenge dosage
form, the drug is dissolved slowly in the mouth and dosing is five times
daily. This paste requires a less-frequent dosing interval.1
Light mineral oil is a transparent, colorless, viscous liquid that is practi-
cally tasteless and odorless when cold; when warm, it has a faint odor.
It is used as an emollient, solvent, lubricant, therapeutic agent, and ole-
aginous vehicle. It has a specific gravity of 0.818 to 0.880. It is insoluble
in water or alcohol. It is miscible with volatile and fixed oils, with the
exception of castor oil. To promote miscibility/solubilization, a small
www.ijpc.com
Formulations
amount of a suitable surfactant can be added. When exposed to heat and
light, it undergoes oxidation with the formation of peroxides and ulti-
mately involving an autocatalytic process. Stabilizers, such as butylated
hydroxyanisole, butylated hydroxytoluene, and alpha-tocopherol can be
used as antioxidants to retard the oxidative process. Mineral oil can be
sterilized by dry heat and should be stored in an airtight container, pro-
tected from light in a cool place. It is incompatible with strong oxidizing
agents.4
Oral Adhesive Paste is composed of gelatin, pectin, xanthan gum,
sodium carboxymethylcellulose (medium viscosity), polyethylene oxide
(WSR-301), and Plasticized Hydrocarbon Gel. Plasticized hydrocar-
bon gel contains light and heavy mineral oil, polyethylene glycol 1450,
and methylcellulose (4000 cps).5 Orabase Plain is a mixture of gela-
tin, pectin, sodium carboxymethylcellulose in hydrocarbon gel with
polyethylene, and mineral oil. It is a non-water-soluble gel that adheres
to mucosal surfaces and body tissues upon application and is used to
provide protection of tissue and for the delivery of pharmaceuticals to
the site of application.5
References
1. United States Pharmacopeial Convention, Inc. USP Pharmacists’
Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention,
Inc.; 2008: 134, 775–779, 1432.
2. McEvoy GK, ed. AHFS Drug Information–2008. Bethesda, MD: Ameri-
can Society of Health-Systems Pharmacists; 2008: 3515–3519.
3. Allen LV Jr. Standard operating procedure for performing physi-
cal quality assessment of ointments/creams/gels. IJPC 1998; 2(4):
308–309.
4. Sheng JJ. Light mineral oil. In: Rowe RC, Sheskey PJ, Quinn ME, eds.
Handbook of Pharmaceutical Excipients. 6th ed. London, UK: Pharma-
ceutical Press; 2009: 447–449.
5. Allen LV Jr. Oral adhesive paste. IJPC 2010; 14(2): 159.
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 153
Formulations

Cyclosporine 10-mg/g in Oral Adhesive Paste

immunosuppressant agent consisting of 11 amino acids produced as a

Rx metabolite by the fungus species Beauveria nivea.4
For 100 g
Oral Adhesive Paste is composed of gelatin, pectin, xanthan gum,
Cyclosporine 1 g sodium carboxymethylcellulose (medium viscosity), polyethylene oxide
Oral Adhesive Paste (Orabase) qs 100 g (WSR-301), and Plasticized Hydrocarbon Gel. Plasticized Hydro-
carbon Gel contains light and heavy mineral oil, polyethylene glycol
1450, and methylcellulose (4000 cps).6 Orabase Plain is a mixture of
Note: The cyclosporine can be obtained as the cyclosporine oral solution (10 mL of gelatin, pectin, sodium carboxymethylcellulose in hydrocarbon gel with
the 100-mg/mL solution can be used). polyethylene, and mineral oil. It is a non-water-soluble gel that adheres
to mucosal surfaces and body tissues upon application and is used to
METHOD OF PREPARATION provide protection of tissue and for the delivery of pharmaceuticals to
1. Calculate the required quantity of each ingredient for the total the site of application.
amount to be prepared.
2. Weigh and/or measure each ingredient accurately. References
3. Place the Oral Adhesive Paste (Orabase can be used if desired) 1. United States Pharmacopeial Convention, Inc. USP Pharmacists’
on a previously cleaned ointment slab or working area. Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention,
4. Place the cyclosporine oral solution on the working area (oint- Inc.; 2008: 775–770.
ment slab) and geometrically incorporate the oral adhesive paste 2. Allen LV Jr. Standard operating procedure for performing physi-
until uniformly mixed. cal quality assessment of ointments/creams/gels. IJPC 1998; 2(4):
5. Place in a catheter-tip syringe or other suitable syringe that can 308–309.
be used to fill small ointment tubes. 3. Ghnassia LT, Yau DF, Kaye KI et al. Stability of cyclosporine in an
6. Fill the paste into 10-g tubes (or other suitable package) from extemporaneously compounded paste. Am J Health-Syst Pharm 1995;
the syringe. 52(20): 2204–2207.
7. Package and label. 4. Tamura T, Takayama K, Satoh H et al. Evaluation of oil/water-type
cyclosporine gel ointment with commercially available oral solution.
PACKAGING Drug Dev and Ind Pharm 1997; 23(3): 285–291.
Package in tight, light-resistant containers.1 5. [No author listed.] Physicians’ Desk Reference. 61st ed. Montvale, NJ:
Thomson PDR; 2007: 2275–2278.
LABELING 6. Allen LV Jr. Oral Adhesive Paste. IJPC 2010; 14(2): 159.
Keep out of reach of children. Use only as directed.

STABILITY
A beyond-use date of 30 days can be used for this preparation.1

USE
This preparation has been used to treat oral lichen planus.

QUALITY CONTROL
Quality-control assessment can include theoretical weight compared
to actual weight, pH, specific gravity, active drug assay, color, texture-
surface, texture-spatula spread, appearance, feel, rheological properties,
and physical observations.2

DISCUSSION
Oral lichen planus is a disease that tends to be chronic, and treatment is
often palliative in nature. This formulation was prepared and studied at
Royal Prince Alfred Hospital in Sydney Australia.3

Cyclosporine A, generally used for the prevention and treatment of

organ transplant rejection, has also shown efficacy in psoriasis and poten-
tial usefulness in other dermatological diseases.4,5 Each mL of Cyclospo-
rine A Oral Solution (Sandimmune Oral Solution) contains cyclosporine
100 mg and alcohol 12.5% dissolved in an olive oil/polyoxyethyl-
ated oleic glycerides vehicle. Cyclosporine A is a cyclic polypeptide

International Journal of Pharmaceutical Compounding www.ijpc.com

154 Vol. 14 No. 2 | March/April 2010

Dexpanthenol 5% Gel-Cream
Rx
For 100 g
Dexpanthenol 5 g
Mineral oil, light 10 mL
Polyethylene glycol 400 15 mL
Pluronic F-127 20 g
Purified water qs 100 g dition polymer of ethylene oxide and water. At room temperature, poly-
Note: When counseling the patient concerning this preparation, it is advisable to
explain its temperature-dependent viscosity. As the preparation is rubbed into the
skin and warms up, it may become slightly more viscous and resistant to rubbing.1
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Dissolve the dexpanthenol and PEG 400 in about 50 mL of puri-
fied water.
4. Add the mineral oil and stir, heating to 60°C to 70ºC.
5. Incorporate the Pluronic F-127 slowly and stir until dissolved.
6. Cool to room temperature.
7. Add sufficient purified water to final weight and mix well.
8. Package and label.
PACKAGING
Package in tight, light-resistant containers.2
LABELING
Keep out of reach of children. Use only as directed.
STABILITY
A beyond-use date of up to 6 months can be used for this preparation.2
USE
Dexpanthenol 5% gel-cream has been used in the treatment of various
skin irritations and disorders.
QUALITY CONTROL
Quality-control assessment can include theoretical weight compared
to actual weight, pH, specific gravity, active drug assay, color, texture-
surface, texture-spatula spread, appearance, feel, rheological properties,
and physical observations.3
DISCUSSION
Dexpanthenol (C9H19NO4, MW 205.25) occurs as a clear, viscous,
somewhat hygroscopic liquid, having a slight characteristic odor. It
is freely soluble in water, alcohol, and propylene glycol, and slightly
soluble in glycerin. Some crystallization may occur. It should be stored
in air-tight containers. It has been used topically in 2% to 5% concen-
trations in the treatment of various minor skin disorders.4
Light mineral oil is a transparent, colorless, viscous liquid that is practi-
cally tasteless and odorless when cold; when warm, it has a faint odor. It
www.ijpc.com
Formulations
has a specific gravity of 0.818 to 0.880. It is insoluble in water or alcohol.
It is miscible with volatile and fixed oils, with the exception of castor oil.
Stabilizers, such as butylated hydroxyanisole, butylated hydroxytoluene,
and alpha-tocopherol can be used as antioxidants to retard the oxidative
process. Mineral oil should be stored in an airtight container, protected
from light in a cool place.5
Polyethylene glycol (Carbowax, PEG, polyoxyethylene glycol) is an ad-
ethylene glycols with molecular weights of 200 to 600 are liquid, and
those with molecular weights greater than 1000 are solid. The density of
the liquid PEGs is in the range of 1.11 to 1.14 g mL. The freezing point
for the PEG 400 is 4°C to 8°C. The polyethylene glycols are all soluble
in water and miscible in all ratios with other PEGs. The liquid PEGs are
soluble in acetone, alcohols, glycerin, and glycols. They are, however,
insoluble in fats, fixed oils, and mineral oil. The PEGs are chemically
stable, do not support microbial growth, and do not become rancid.6
Pluronic F-127 is a poloxamer. Poloxamers are a series of closely
related block copolymers of ethylene oxide and propylene oxide that are
used as emulsifying agents, solubilizing agents, and wetting agents. They
are available in different grades, either liquids or solids with average
molecular weights ranging from 2,090 to 14,600. The poloxamers are
stable, and aqueous solutions are stable in the presence of acids, alkalis,
and metal ions; the aqueous solutions do support mold growth. Polox-
amer 407 (Pluronic F-127) is generally available in powdered form. It is
either odorless or may have a very mild odor. It melts at about 56ºC and
is freely soluble in water, alcohol, and isopropyl alcohol.7
References
1. Collett JH. Poloxamer. In: Rowe RC, Sheskey PJ, Quinn ME, eds.
Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: Ameri-
can Pharmaceutical Association; 2009: 506–509.
2. United States Pharmacopeial Convention, Inc. USP Pharmacists’
Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention,
Inc.; 2008: 775–779.
3. Allen LV Jr. Standard operating procedure for performing physi-
cal quality assessment of ointments/creams/gels. IJPC 1998; 2(4):
308–309.
4. Sweetman SC, ed. MARTINDALE: The Complete Drug Reference. 35th ed.
London, UK: Pharmaceutical Press; 2007: 2142.
5. Sheng JJ. Light mineral oil. In: Rowe RC, Sheskey PJ, Quinn ME, eds.
Handbook of Pharmaceutical Excipients. 6th ed. London, UK: Pharmaceu-
tical Press; 2009: 447–449.
6. Wallick D Polyethylene glycol. In: Rowe RC, Sheskey PJ, Quinn ME,
eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC:
American Pharmaceutical Association; 2009: 517–522.
7. Collett JH. Poloxamer. In: Rowe RC, Sheskey PJ, Quinn ME, eds.
Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: Ameri-
can Pharmaceutical Association; 2009: 506–509.
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 155
Formulations
Lamotrigine 25-mg/mL Injection
Rx
For 100 mL
Lamotrigine 2.5 g
Mannitol 3.8 g
Methanesulfonic acid 937 mg
Sodium hydroxide qs pH 3.3 to 3.5
Sterile water for injection qs 100 mL
Note: This formulation should be prepared according to strict aseptic compound-
ing technique in a laminar airflow hood in a cleanroom or via isolation barrier
technology by a compounding pharmacist who is validated in aseptic compounding.
This is a high-risk preparation.
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Dissolve the mannitol in about 90 mL of sterile water for injection.
4. Add the lamotrigine followed by the methanesulfonic acid.
5. Adjust the pH of the solution to the range of pH 3.3 to 3.5.
6. Add sufficient sterile water for injection to volume.
7. Filter through an appropriate sterile 0.2 micron filter into sterile vials.
8. Package and label.
PACKAGING
Package in tight, light-resistant containers.1
LABELING
Keep out of reach of children. Use only as directed.
STABILITY
A beyond-use date of 7 days can be used if a sterility testing program is
in place.1
USE
Lamotrigine is used in the treatment of seizures.
QUALITY CONTROL
Quality-control assessment can include weight/volume, physical obser-
vation, pH, specific gravity, osmolality, assay, color, clarity, particulate
matter, sterility, and pyrogenicity.2,3
DISCUSSION
Lamotrigine (C9H7Cl2N5, MW 256.09, Lamictal) is a phenyltriazine
anticonvulsant that differs structurally from other anticonvulsants. It is
used in combination with other anticonvulsant agents to manage partial
seizures in both adults and children. It occurs as a white to pale cream-
colored powder and has a pKa of 5.7. Lamotrigine is very slightly soluble
in water (0.17 mg/mL at 25°C) and slightly soluble in 0.1 M hydrochlo-
ride (4.1 mg/mL at 25°C).4
Mannitol (C6H14O6, MW 182.17) occurs as a white, crystalline powder
or as free-flowing granules. It is odorless and has a sweet taste. It is freely
International Journal of Pharmaceutical Compounding
156 Vol. 14 No. 2 | March/April 2010
soluble in water, soluble in alkaline solutions, and very slightly soluble
in alcohol. It is used as a sweetening agent, tablet and/or capsule diluent,
tonicity-adjusting agent, and as a bulking agent for freeze-drying. It
is preserved in well-closed containers. It has a melting range between
164°C and 169°C.1
Methanesulfonic acid (CH4O3S, MW 96.10) is an aliphatic organic
compound that occurs as a colorless to yellowish liquid. It is soluble in
water and alcohol. It has a density of 1.483, melting point of 20ºC, and a
boiling point of 167ºC. It is used in parenterals to form the mesylate salt
or ester of selected drugs.5
Sodium hydroxide (NaOH, MW 40.00, caustic soda, soda lye) occurs
as dry, very deliquescent, white or almost white sticks, pellets, or fused
masses which are hard and brittle. It is strongly alkaline and corrosive
and rapidly absorbs moisture and carbon dioxide when it is exposed
to air. It is soluble 1 g in 1 mL of water and is freely soluble in alcohol.
A 0.01% solution in water has a pH of not less than 11.0. It should be
stored in airtight, nonmetallic containers.6,7
Sterile water for injection is water for injection that has been sterilized
and suitably packaged; it contains no added substances. Water for injec-
tion is water purified by distillation or by reverse osmosis and contains
no added substances. Note that water for injection is not prepared by
an ion exchange process. Water has a specific gravity of 0.9971 at room
temperature, a melting point at 0ºC, and a boiling point at 100ºC. It is
miscible with most polar solvents and is chemically stable in all physical
states (ice, liquid, steam).8
References
1. United States Pharmacopeial Convention, Inc. USP Pharmacists’
Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Conven-
tion, Inc.; 2008: 775–779, 797–831, 1446.
2. Allen LV Jr. Standard operating procedure for particulate testing for
sterile products. IJPC 1998; 2(1): 78.
3. Allen LV Jr. Standard operating procedure: Quality assessment for
injectable solutions. IJPC 1999; 3(5): 406–407.
4. Lamotrigine [product information]. Available at: www.rxlist.com/
lamictal-drug.htm. Accessed January 21, 2010.
5. Ash M, Ash I. Handbook of Pharmaceutical Additives. 3rd ed. Endicott,
NY: Synapse Information Resources, Inc.; 2007: 731.
6. Kibbe AH. Sodium hydroxide. In: Rowe RC, Sheskey PJ, Quinn ME,
eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC:
American Pharmaceutical Association; 2009: 648–649.
7. Reynolds JE, ed. MARTINDALE: The Extra Pharmacopeia. 30th ed.
London, UK: The Pharmaceutical Press; 1993: 1415.
8. Dubash D, Shah U. Water. In: Rowe RC, Sheskey PJ, Quinn ME, eds.
Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: Ameri-
can Pharmaceutical Association; 2009: 766–770.
www.ijpc.com

Metolazone 10-mg/mL Injection
Rx
For 100 mL
Metolazone 1 g solvent in injectable and oral liquids (variable concentration), and as a
Ethanol, 95% 10 mL
Propylene glycol 65 mL
Sterile water for injection qs 100 mL
Note: This formulation should be prepared according to strict aseptic compound-
ing technique in a laminar airflow hood in a cleanroom or via isolation barrier
technology by a compounding pharmacist who is validated in aseptic compounding.
This is a high-risk preparation.
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Place the propylene glycol in a suitable vehicle.
4. Add the metolazone and heat to about 50ºC and mix until dissolved.
5. Cool the solution to 25°C.
6. Add the ethanol and mix well.
7. Add sufficient sterile water for injection to volume and mix well.
8. Filter through an appropriate sterile 0.2 micron filter into sterile vials.
9. Package and label.
PACKAGING
Package in tight, light-resistant containers.1
LABELING
Keep out of reach of children. Use only as directed.
STABILITY
A beyond-use date of 14 days can be used for this preparation if a pro-
gram of sterility testing is in place.1
USE
Metolazone is used in the treatment of edema and hypertension.2
QUALITY CONTROL
Quality-control assessment can include weight/volume, physical obser-
vation, pH, specific gravity, osmolality, assay, color, clarity, particulate
matter, sterility, and pyrogenicity.3,4
DISCUSSION
Metolazone is used in the treatment of edema and hypertension. It
may be more effective than other thiazide-like diuretics in edematous
patients with impaired renal function.2
Metolazone (C16H16ClN3O3S, MW 365.84) is a quinazoline-derivative
diuretic that is structurally and pharmacologically similar to quine-
thazone and the thiazides. It occurs as a white powder that is practically
insoluble in water and sparingly soluble in alcohol. It has a pKa of 9.7. It
is commercially available as 2.5-mg, 5-mg, and 10-mg tablets (Zarox-
olyn).2
www.ijpc.com
Formulations
Alcohol (C2H5OH, MW 46.07, ethyl alcohol, ethanol, grain alcohol)
is a clear, colorless mobile and volatile liquid with a slight, character-
istic odor and a burning taste. It is used as an antimicrobial preserva-
tive (>10% concentration), disinfectant (60% to 90% concentration),
solvent in topical products (60% to 90% concentration). Alcohol USP
refers to 95% ethanol and dehydrated alcohol refers to 99.5% alcohol.
Its specific gravity is between 0.812 and 0.816, and its boiling point is
78.15°C. It is miscible with chloroform, glycerin, and water and its solu-
tions may be sterilized by autoclaving or by filtration. It should be stored
in a cool place.5
Propylene glycol (C3H8O2, MW 76.09) occurs as a clear, colorless, vis-
cous, practically odorless liquid with a sweet taste, somewhat resembling
glycerin. It has a specific gravity of 1.038 g/mL and is miscible with
acetone, chloroform, 95% ethanol, glycerin, and water. It is not miscible
with fixed oils or light mineral oil. It will, however, dissolve some es-
sential oils. Propylene glycol is used as a humectant in topicals (~15%
concentration), preservative in solutions and semisolids (15% to 30%
concentration), and as a solvent or cosolvent in aerosols (10% to 30%
concentration), oral solutions (10% to 25% concentration, parenterals
(10% to 60% concentration), and topicals (5% to 80% concentration).
Propylene glycol is actually a better solvent than glycerin. It is similar to
ethanol as an antiseptic and is also used in cosmetics and in the food in-
dustry as a vehicle for flavors and as a vehicle for emulsifiers. It is stable
and may be mixed with numerous other solvents. Aqueous solutions of
propylene glycol can be sterilized by autoclaving. Since propylene glycol
is hygroscopic, it should be stored in an airtight container and protected
from light. Incompatibilities include potassium permanganate.6
Sterile water for injection is water for injection that has been steril-
ized and suitably packaged; it contains no added substances. Water for
injection is water purified by distillation or by reverse osmosis (RO)
and contains no added substances. Note that water for injection is not
prepared by an ion exchange process. Water is used to describe potable
water from a public water supply that is suitable for drinking and is the
beginning point of the official waters. It is a clear, colorless, odorless, and
tasteless liquid. Purified water is water that is obtained by distillation, ion
exchange, RO, or some other suitable process. Water has a specific grav-
ity of 0.9971 at room temperature, a melting point at 0ºC and a boiling
point at 100ºC. It is miscible with most polar solvents and is chemically
stable in all physical states (ice, liquid, steam).7
References available upon request.
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 157
Formulations
Plasticized Hydrocarbon Gel
Rx
For 100 g
Mineral oil, light:heavy 1:1 90 g
Polyethylene glycol 1450 5 g
Methylcellulose (4000 cps) 5 g
Note: The ratios of the ingredients can be adjusted as needed.
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Heat the mineral oil blend to about 35ºC.
4. Incorporate the PEG 1450 and maintain the temperature until
the PEG is melted and mixed well.
5. Add the methylcellulose, cool the mixture, and allow the mixture
to gel.
6. Package and label.
PACKAGING
Package in tight, light-resistant containers.1
LABELING
Keep out of reach of children. Use only as directed.
STABILITY
A beyond-use date of up to 6 months can be used for this preparation.1
USE
Plasticized hydrocarbon gel is used in the preparation of oral adhesive
paste.
QUALITY CONTROL
Quality-control assessment can include theoretical weight compared to
actual weight, pH, specific gravity, color, texture-surface, texture-spatula
spread, appearance, feel, rheological properties, and physical observations.2
DISCUSSION
Light mineral oil is a transparent, colorless, viscous liquid that is practi-
cally tasteless and odorless when cold; when warm, it has a faint odor. It
has a specific gravity of 0.818 to 0.880. It is insoluble in water or alcohol.
It is miscible with volatile and fixed oils, with the exception of castor
oil. To promote miscibility/solubilization, a small amount of a suitable
surfactant can be added. When exposed to heat and light, it undergoes
oxidation with the formation of peroxides and ultimately involving an
autocatalytic process. Stabilizers, such as butylated hydroxyanisole,
butylated hydroxytoluene, and alpha-tocopherol can be used as antioxi-
dants to retard the oxidative process.3
Mineral oil (heavy mineral oil, liquid paraffin, liquid petrolatum, paraf-
fin oil, white mineral oil) is a transparent, colorless, viscous liquid that
is practically tasteless and odorless when cold; when warm, it has a faint
odor. It has a specific gravity of 0.845 to 0.905 and a boiling point of
International Journal of Pharmaceutical Compounding
158 Vol. 14 No. 2 | March/April 2010
greater than 360ºC. It is practically insoluble in 95% ethanol, glycerin,
and water. It is soluble in acetone, chloroform, and petroleum ether. It
is miscible with volatile and fixed oils, with the exception of castor oil.
To promote miscibility/solubilization, a small amount of a suitable
surfactant can be added. Stabilizers, such as butylated hydroxyanisole,
butylated hydroxytoluene, and alpha-tocopherol can be used as antioxi-
dants to retard the oxidative process.3
Polyethylene glycol (carbowax, PEG, polyoxyethylene glycol) is an
addition polymer of ethylene oxide and water. At room temperature,
polyethylene glycols with molecular weights of 200 to 600 are liquid,
and those with molecular weights greater than 1000 are solid. The liquid
polyethylene glycols are clear, colorless, or slightly yellow-colored,
viscous liquids with a slight, but characteristic odor and a bitter, slightly
burning taste. Solid polyethylene glycols are white or off-white pastes
or waxy flakes. The polyethylene glycols are all soluble in water and
miscible in all ratios with other PEGs. The PEGs are chemically stable,
do not support microbial growth, and do not become rancid.4
Methylcellulose (Methocel) is a practically odorless and tasteless, white
to yellowish-white colored granule or powder that is widely used in both
oral and topical formulations. It is available in different viscosity grades
with the low viscosity grades being used to emulsify oils, as suspending
and thickening agents for oral liquids, and the higher viscosity grades
used to thicken topically applied products such as creams and gels.
The pH of a 1% solution is in the range of 5.5 to 8.0. It is hygroscopic,
practically insoluble in acetone, ethanol, saturated salt solutions, and
hot water, and soluble in glacial acetic acid. In cold water, it swells and
disperses to form a viscous, colloidal dispersion.5
References
1. United States Pharmacopeial Convention, Inc. USP Pharmacists’
Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention,
Inc.; 2008: 775–779.
2. Allen LV Jr. Standard operating procedure for performing physi-
cal quality assessment of ointments/creams/gels. IJPC 1998; 2(4):
308–309.
3. Sheng JJ. Light mineral oil; Mineral oil. In: Rowe RC, Sheskey PJ,
Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. London,
UK: Pharmaceutical Press; 2009: 445–449.
4. Wallick D. Polyethylene glycol. In: Rowe RC, Sheskey PJ, Quinn ME,
eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC:
American Pharmaceutical Association; 2009: 517–522.
5. Allen LV Jr, Luner PE. Methylcellulose. In: Rowe RC, Sheskey PJ,
Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. Washing-
ton, DC: American Pharmaceutical Association; 2009: 438–441.
www.ijpc.com
 Formulations

Oral Adhesive Paste

alcohol or in diluted alcohol, and in other organic solvents. Pectin dis-

Rx solves in water more readily if it is first moistened with alcohol, glycerin,
or simple syrup, or if it is first mixed with three or more parts of sucrose.
For 100 g
Pectin USP differs from the commercial food pectin standardized to a
Gelatin 2 g “150 jelly grade” by the addition of dextrose or other sugars and some-
Pectin 2 g times sodium citrate or other buffer salts.1
Xanthan gum 1 g
Sodium carboxymethylcellulose (med visc) 4 g Xanthan gum (corn sugar gum) is a high molecular weight polysac-
Polyethylene oxide (WSR-301) 5 g charide gum with a molecular weight of approximately 2 × 106. Xanthan
Plasticized Hydrocarbon Gel qs 100 g gum occurs as a cream or white-colored, odorless, free-flowing fine
powder. It is soluble in cold or warm water but is practically insoluble in
ethanol and ether.4
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
Sodium carboxymethylcellulose (med visc) occurs as a white to
amount to be prepared.
cream-colored, hygroscopic powder or granules. It is easily dispersed
2. Weigh and/or measure each ingredient accurately.
in water to form colloidal solutions; it is insoluble in alcohol. The pH
3. Mix the gelatin, pectin, xanthan gum, sodium carboxymethylcel-
of a 1% aqueous solution is between 6.5 and 8.5. It is incompatible with
lulose, and polyethylene oxide in a mortar.
strongly acidic solutions, with soluble salts of iron and some other met-
4. Weigh about 50 g of plasticized hydrocarbon gel and heat using
als, and with xanthan gum.5
low heat with stirring.
5. Remove from heat, then geometrically incorporate the powder
Polyethylene oxide (Polyox, WSR-301) is a nonionic homopolymer
mixture from step #3.
of ethylene oxide, represented by the formula (OCH2CH2)n and occurs
6. Add sufficient additional plasticized hydrocarbon gel to final
as a white to off-white free-flowing powder, with a slight ammoniacal
weight and mix until uniform.
odor. It should be preserved in tight, light-resistant containers. It should
7. Package and label.
be labeled to indicate its viscosity profile and the name and quantity of
any added antioxidant. Polyethylene oxide strongly bonds with water, is
PACKAGING
nonionic, and undergoes salting-out effects.1,6
Package in tight, light-resistant containers.1
Plasticized hydrocarbon gel contains light and heavy mineral oil,
LABELING
polyethylene glycol 1450 and methylcellulose (4000 cps).7
Keep out of reach of children. Use only as directed.
References
STABILITY
1. United States Pharmacopeial Convention, Inc. USP Pharmacists’
A beyond-use date of up to 6 months can be used for this preparation.1
Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Conven-
tion, Inc.; 2008: 275, 287, 775–779, 1455.
USE
2. Allen LV Jr. Standard operating procedure for performing physi-
Oral Adhesive Paste is used as a vehicle for medications applied to the
cal quality assessment of ointments/creams/gels. IJPC 1998; 2(4):
mucosal surfaces of the mouth.
308–309.
3, Podczeck F. Gelatin. In: Rowe RC, Sheskey PJ, Quinn ME, eds.
QUALITY CONTROL
Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC:
Quality-control assessment can include theoretical weight compared
American Pharmaceutical Association; 2009: 278–281.
to actual weight, pH, specific gravity, active drug assay, color, texture-
4. Shah HC, Singh KK. Xanthan Gum. In: Rowe RC, Sheskey PJ,
surface, texture-spatula spread, appearance, feel, rheological properties,
Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. Wash-
and physical observations.2
ington, DC: American Pharmaceutical Association; 2009: 782–785.
5. Hooton JC. Carboxymethylcellulose sodium. In: Rowe RC, Sheskey
DISCUSSION
PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed.
Gelatin (Pharmagel A, Pharmagel B) occurs as a light-amber to faintly
Washington, DC: American Pharmaceutical Association; 2009:
yellow-colored vitreous, brittle solid that is practically odorless and
118–121.
tasteless. It is available as translucent sheets and granules or as a powder.3
6. Maximilien JS. Polyethylene oxide. In: Rowe RC, Sheskey PJ, Quinn
ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. Washington,
Pectin is a purified carbohydrate obtained from a dilute acid extract of
DC: American Pharmaceutical Association; 2009: 522–524.
the inner portion of the rind of citrus fruits or from apple pomace. It
7. Allen LV Jr. Plasticized Hydrocarbon Gel. IJPC 2010; 14(2): 158.
occurs as a coarse or fine powder that is yellowish white in color. Pectin
is odorless and has a mucilaginous taste. It is almost completely soluble
in 20 parts of water and forms a viscous, opalescent, colloidal solution
that readily flows and is acid to litmus. Pectin is practically insoluble in

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 159
 Peer Reviewed
Chemical Stability of Hydromorphone
Hydrochloride in Patient-Controlled
Analgesia Injector
Dristi Khondkar, PhD
Poonam Chopra, MS
College of Pharmacy
University of Cincinnati
Cincinnati, Ohio
John P. McArter, PharmD
Joseph A. Rosen, CPhT
University Hospital
University of Cincinnati
Cincinnati, Ohio
S. Kevin Li, PhD
College of Pharmacy
University of Cincinnati
Cincinnati, Ohio
Introduction
Intravenous (IV) administration of opioids
has been a common practice for many years
to deliver small boluses of opioids to produce
immediate analgesia.1-3 Patient-controlled an-
algesia (PCA) uses an electrically controlled
infusion pump which delivers a prescribed
amount of IV analgesia to the patient via ac-
tivation. It is more comfortable than the con-
ventional IV analgesia.4-7 PCA is programmed
per the physician's order for the amount and
interval between doses and "locks out" the
patient if he or she attempts to self administer
too often.4,6 It is very effective for post-oper-
ative pain as well as chronic malignant and
non-malignant pain in cases when the patients
are not able to take oral medication.2-3,8-11
Hydromorphone hydrochloride is an ideal
opioid for IV administration due to its anal-
gesic efficacy and potency.12 Hydromorphone
is a semi-synthetic hydrogenated ketone of
morphine. It has similar opioid-receptor
selectivity to morphine.13 It is an excellent
alternative to morphine and is approximately
five times more analgesic14-16 and potent than
morphine17 when given by the oral route, and
International Journal of Pharmaceutical Compounding
160 Vol. 14 No. 2 | March/April 2010
Abstract
The chemical stability of hydromorphone hydrochloride in patient–con-
trolled analgesia injectors was studied for 34 weeks at different tempera-
tures.The sterility of the solution was also monitored at the end of 16-week
storage. For the determination of stability of hydromorphone, five groups
of six patient–controlled analgesia injectors containing hydromorphone
solutions of 0.2 mg/mL (6 mg of drug solution in 30 mL 0.9% normal sa-
line) sealed with plastic tip caps were stored at 5ºC in refrigerator, 20ºC
on benchtop, 20ºC in dark, 35ºC in dark, and 50ºC in dark. Chemical stabil-
ity was determined throughout a storage period of 34 weeks using high
performance liquid chromatography. Sterility test was also performed at
16 weeks. Hydromorphone solutions stored in different conditions up to
34 weeks remained clear and free of visible precipitation throughout the
study. After 8 weeks of storage in the patient–controlled analgesia injec-
tors in different temperature conditions, the concentrations of hydromor-
phone in all the samples remained >95% of their original value. At 16 and
34 weeks, the concentration of hydromorphone in the injectors decreased
to 92% to 96% and 86% to 88% of their original value, respectively. In the
sterility test of bacterial contamination of the hydromorphone solutions in
the patient–controlled analgesia injectors at 16 weeks, none of the injec-
tor solutions showed evidence of microbial growth after 14 days of incu-
bation in fluid thioglycolate medium. This study demonstrates the stabil-
ity and sterility of hydromorphone hydrochloride solution.
8.5 times more potent than morphine when As the storage conditions such as containers,
given intravenously.18 The duration of action temperature, and excipients (excipient con-
of hydromorphone is approximately four to centrations) can affect drug stability, there is
five hours and plasma half-life is two to three no information in the literature that supports
hours, which are comparable to morphine.13,19 the long-term stability of hydromorphone in
Hydromorphone is more lipid-soluble and PCA injectors. It is important that the drug
has fewer active metabolites than morphine. solutions remain stable at the temperature
Because of its greater lipophilicity, hydro- they may experience during storage and
morphone has comparatively faster onset and shipping (5ºC to 40ºC). The sterility of the
shorter duration of action than morphine solution in hydromorphone PCA injectors is
in supraspinal distribution and has minimal another requirement for the long-term storage
adverse side effects.20 of these injectors. Usually, PCA injectors are
Whereas the chemical stability of hy- prepared extemporaneously by anesthetists,
dromorphone in plastic bags, glass vials, pharmacists, or nursing staff the day before
polypropylene infusion pump syringes, and they are administered, which is time consum-
elastomeric reservoir pumps has been estab- ing and can increase error and/or risk of
lished,21 the chemical stability of hydromor- contamination. They have an expiration of
phone in normal saline in PCA injectors and two days according to United States Phar-
their compatibility have not been studied. macopeial Convention guidelines. Labor cost
www.ijpc.com

and wastage also become important issues.
The purpose of this study was to investigate
the chemical stability and sterility of these
ready-to-use PCA injectors after they were
prepared in a hospital pharmacy under aseptic
conditions.
Materials and
Methods
Hydromorphone hydrochloride injectable,
2-mg/mL, 20-mL multiple dose vial (Lot
018106, NDC 0641-2341-41) was purchased
from Baxter Healthcare Corporation (Deer-
field, Illinois). PCA injectors were purchased
from Hospira (Lot 62-137-R1 and 66-247-R1,
30-mL single use empty vial and injector, List
No. 6021-03; Lake Forest Illinois). Hydromor-
phone standard was from Cerilliant Corpora-
tion (Lot FE050708-01; Round Rock, Texas).
High-performance liquid chromatographic-
grade acetonitrile, methanol, glacial acetic
acid, and analytical-grade sodium laurel
sulfate (SLS) were purchased from Fisher Sci-
entific (Lots 062507, 042177, 48039, 974577,
respectively; Florence, Kentucky). Diethyl
amine was from Alfa Aesar (Lot E07S052;
Ward Hill, Massachusetts).
Preparation of the
PCA Injectors
Stock hydromorphone solution (0.2 mg/
mL) was prepared by adding 90 mL of 2-mg/
mL hydromorphone hydrochloride to 810
mL 0.9% normal saline (Sodium Chloride,
Injection USP) in a 1000-mL sterile container
(Lot 830408, Exacta-Mix EVA; Baxa Corpora-
tion, Englewood, Colorado). The filling pump
was fitted with sterile single lead, luer-lock
tubing (Lot 01110508; Excelsior Medical,
Neptune, New Jersey) and connected to the
stock solution. The set volume for the pump
was 30-mL/injector. The PCA injector was
prepared for filling by depressing the plunger
to remove excess air from the chamber. This
was connected to the stock solution tubing
to fill the injector with 30-mL stock solution
and capped with a Baxa luer lock tip cap. The
entire procedure was performed under sterile
condition by a technician in sterile gown, with
hair, gloves, and feet covers in an International
Organization for Standardization (ISO) Class
5 vertical laminar airflow hood (Model: NU-
425-600, Biological Safety Cabinet: NuAire,
Plymouth, Minnesota) located in an ISO Class
7 cleanroom.
www.ijpc.com
Drug-material
Stability Test
Five groups of six hydromorphone PCA
injectors were prepared and kept in five differ-
ent conditions: the hydromorphone injectors
were incubated at 5ºC in a refrigerator, 20ºC
on benchtop, and exposed to normal daylight,
20ºC in dark, 35ºC in dark, and 50ºC in dark.
Hence, six hydromorphone PCA injectors
were tested under each condition. Hydromor-
phone solution in its originally sealed glass
vial (as it was supplied from the manufacturer)
maintained at room temperature and protected
from light was the control. The concentration
of hydromorphone was determined with high-
performance liquid chromatography (HPLC).
Then, the concentration of hydromorphone
was determined at 1, 2, 4, 7 days and 2, 4, 8, 16,
and 34 weeks. Briefly, solution samples were
collected from the PCA injectors (6 samples ×
5 conditions at each time point), diluted three-
fold by the mobile phase, and analyzed with
HPLC. Triplicate HPLC determinations were
performed for each of the 30 samples collected
at each time point. Two analytical methods
were used: the first method was adapted from
the British Pharmacopeia23 with some modifi-
cations and served as the main method, and
the second method was a stability-indicating
method from the literature24 to check the
results (the samples at 34 weeks were analyzed
with both the first and second methods and
the results were compared). There was no sig-
nificant difference (±1%) between the results
of 34 weeks from the first and second HPLC
methods.
The HPLC system consisted of a Shimadzu
LC SIL-20A autosampler, LC-20AT pump,
SPD-20A UV-Vis detector, and a Varian
Microsorb-MV 100-5 C18 column (150 mm ×
4.6 mm, 5 mcm). The column was kept at room
temperature (~23°C), the detector was set
at 284 nm, flow rate of the mobile phase was
constant at 1 mL/min, and sample injection
volume was 10 mcL. In the first method, the
mobile phase was 80:10:10 (v/v) water-ace-
tonitrile-methanol containing 1.9% dieth-
ylamine and 0.29% sodium laurilsulfate and
adjusted to pH 3.0 with phosphoric acid. In the
second method, the mobile phase was 1 L of
60:40 (v/v) water-acetonitrile mixed with 5.5 g
SLS and 11 mL of glacial acetic acid. Calibra-
tion curves were prepared in the mobile phase
at 0.002 to 0.2 mg/mL and based on peak area
measurements. The methods displayed good
linearity (correlation coefficient = 1.00) in
the calibration curves and precision for the
International Journal of Pharmaceutical Compounding
Peer Reviewed
samples (coefficient of variation <3%). All
chromatographs used to determine the con-
centration of hydromorphone had peak area/
height ratios within ±4% of the mean. The
pH of the samples was also monitored with pH
indicator strips (ColorpHast; EMD Chemicals,
Gibbstown, New Jersey) and occasionally
checked with a pH meter (pH/con 510 series,
Oakton, Vernon Hills, Illinois).
To confirm the hydromorphone peak in the
HPLC assay, HPLC fractionation and liquid
chromatography-mass spectrometry (LC-MS)
were carried out with the stock solution sam-
ples. Samples of eluent from the detector were
collected in the HPLC assay (the first method)
described above and analyzed with a liquid
chromatography-mass spectrometer (Model
Micromass ZQ 4000; Waters Corporation,
Milford, Massachusetts). The LC-MS system
had a Gemini C18 column (100 mm × 3 mm, 3
mcm; Phenomenex, Torrance, California), col-
umn temperature ~23°C, ultraciolet-viscosity
detector, mass spectrometry operated using
electrospray ionization in both the positive
(ESI+) and negative ionization mode (ESI-),
and MassLynx 4.0 software. The mobile phase
was 0.1% formic acid in water as solvent A and
acetonitrile as solvent B with solvent gradient
increasing the percentage of solvent B from
5% to 100% in the first 12 minutes and 100%
solvent B from 12 to 18 minutes.
Stress Test
A simplified stress test of the hydromor-
phone solution was performed under pro-
longed heating at 80°C. The hydromorphone
hydrochloride solution was prepared by dilut-
ing the 2-mg/mL hydromorphone hydrochlo-
ride injectable similar to the method described
in this article (Preparation of the PCA
Injectors) in a capped glass vial. The samples
were kept in an oven at 80°C for 24, 48, and 96
hours, withdrawn at the designated time points
and analyzed using HPLC. This test was done
in triplicate. The purpose of this stress test
was to show that significant drug degradation
would eventually occur under the present stor-
age conditions. The stress test results were not
used to quantify hydromorphone degradation.
Sterility Test
Sterility test was performed according to
the method described in the British Pharmaco-
peia.25 The test was carried out under aseptic
conditions using fluid thioglycollate culture
medium, suitable for detecting anaerobic
Vol. 14 No. 2 | March/April 2010 161
Peer Reviewed

Table 1. Percent of Initial Hydromorphone Concentration Remaining in the Solution in the PCA Injectors
Over Time Under the Stated Conditions (Mean ± Standard Deviation, n = 6).
Time (days) 5˚C, in Refrigerator 20˚C, on Benchtop 20˚C, in Dark 35˚C, in Dark 50˚C, in Dark
1 98.8 ± 2.3 99.2 ± 2.0 99.7 ± 1.7 101.1 ± 0.9 98.9 ± 0.9
2 99.4 ± 1.5 99.1 ± 1.6 99.4 ± 0.5 99.4 ± 0.3 99.6 ± 1.0
4 99.5 ± 1.0 99.5 ± 1.0 99.2 ± 1.6 99.6 ± 0.5 100.4 ± 0.6
7 99.8 ± 1.0 100.9 ± 1.7 99.0 ± 1.6 100.4 ± 0.5 100.8 ± 1.0
14 97.8 ± 1.5 98.1 ± 1.1 98.6 ± 1.6 100.8 ± 0.6 97.4 ± 1.5
28 98.1 ± 1.8 97.6 ± 2.2 98.0 ± 2.8 97.4 ± 0.1 97.2 ± 0.7
56 98.4 ± 3.9 99.6 ± 2.9 98.1 ± 1.5 97.2 ± 1.3 98.0 ± 0.7
112 94.7 ± 1.5 96.4 ± 1.1 95.4 ± 2.7 96.1 ± 0.9 92.3 ± 0.8
238 88.3 ± 3.0 88.3 ± 1.6 88.5 ± 1.4 86.9 ± 0.3 86.3 ± 1.4

9.283
Retention Time
and aerobic bacteria. Three injectors (n = 3) were randomly selected 75 -

--------------------

--------------------

--------------------
--------------------
a
from each condition discussed in this article (Drug-material Stability
50 -
Test) at 16 weeks for the sterility test. A small amount of the hydro- Volts

6.383
1.250

2.842
morphone solution (0.3 mL) from each injector was transferred directly

1.683
25 -

2.525

4.908
into the culture medium (3 mL) so the volume of the sample was not
more than 10% of the volume of the medium. To compare the sterility 0-

of the hydromorphone solutions, positive control of sterile water (n =

2.833
3), negative control of tap water (n = 3), and hydromorphone solution 150- Retention Time
control prepared directly from the injectable bottle without storage were b
also incubated under the same condition. The inoculated media was 100-
incubated for 14 days at 37ºC. The cultures were observed several times
Volts

9.200
during the incubation period.

6.350
1.258

50-
1.692

2.333
2.492

3.233
1.883

3.992

Results
Drug-stability Test
Table 1 shows that the hydromorphone solutions in PCA injectors
were relatively stable up to 34 weeks of storage under the conditions
tested in the present study (5ºC in refrigerator, 20ºC on benchtop,
20ºC in dark, 35ºC in dark, and 50ºC in dark). At 16 weeks, none of
the hydromorphone samples analyzed demonstrated a significant loss
of more than ~5% hydromorphone from their original concentra-
tion, except those stored at 50ºC. At 34 weeks, the concentration of
hydromorphone in the injectors decreased to ~86% to 88% of their
original value. Also, there was no photodegradation observed in the
samples stored on the benchtop exposed to daylight at room tempera-
ture, and all sample remained free of visible particles and practically
colorless throughout the study. The pH of the solutions in the injectors
remained constant between pH 6.5 to 7.5 throughout the study, except
those stored at 35ºC and 50ºC, which exhibited pH 7.5 to 8.5 after 34
weeks. The control in the original injectable vial (as it was supplied
from the manufacturer), kept in the dark and at room temperature,
demonstrated hydromorphone concentration of 100% from 1 to 8
weeks and 99.8% at 16 weeks. HPLC chromatograms of hydromor-
phone solutions exposed to PCA injectors and at different temperature
conditions revealed no additional peaks. No significant temperature
dependency upon the rate of hydromorphone degradation was ob-
served within the range of the temperature studied possibly due to the
small percentage of degradation and experimental uncertainties (see
Table 1).
0- 4.867
0 1 2 3 4 5 6 7 8 9 10
Minutes
Figure 1. Representative chromatograms obtained
after the hydromorphone samples were kept in 80˚C
for (a) 24 hours and (b) 96 hours. The fluctuation
in the baseline between 1.2 and 1.7 minutes in the
chromatograms and the resulting errors in peak
integration before 4 minutes did not affect the results
in Table 1 as the stress test data were not used to
quantify hydromorphone degradation in the present
study. In a few occasions in the stress test when
the peak at 2.8 minutes became significant, peak
integration at the later retention time could also be
affected, but this interference did not occur in the
chromatograms in the hydromorphone stability study.
Stress Test
After 48 hours of exposure to heat (80ºC), physical changes of the hy-
dromorphone solutions were visually observed as the solutions became
reddish in color. The HPLC chromatograms of the samples revealed a
significant additional peak at around 2.8 minutes believed to be a degra-
dation product (Figure 1).

International Journal of Pharmaceutical Compounding www.ijpc.com

162 Vol. 14 No. 2 | March/April 2010
 Peer Reviewed
Fig. 1

e i m q
a
Negative controls

j n r
b f

Positive controls
k o
c g

p
d h l

Figure 2. Representative photo of the sterility test of the hydromorphone solutions after 16 week storage at
different temperatures (a, b, c--20˚C on benchtop, d, e, f--20˚C in dark, g, h, i--35˚C in dark, j, k, l--50˚C in dark,
and m, n, o--5˚C in refrigerator) and freshly prepared without storage (p, q, r--hydromorphone solution control).
The negative and positive controls are also shown.
Fig. 2

Sterility Test
After 24 hours incubation, there was clear evidence of microbial
growth in the negative controls, but positive controls remained clear
throughout the incubation period. After 14 days of incubation, there was
no evidence of microbial growth in the hydromorphone solutions drawn
13chronic pain, which can save labor cost, avoid wastage, and reduce error
from the PCA injectors at 16 weeks, which complies with the test for
sterility (Figure 2).
Discussion
Hydromorphone is a potent analgesic and is commonly given via the
IV route using PCA. The stability and sterility of hydromorphone in
PCA injectors after long storage at different temperatures has not been
established in the literature. To our knowledge, this is the first report
that specifically addresses the stability and sterility of hydromorphone
solution stored in PCA injectors. Lawrence and colleagues22 suggested
that hydromorphone is stable while packaged in plastic syringes in re-
frigeration, at room temperature, and body temperatures for 2 days and
60 days. The results in the present study indicate that hydromorphone
solution prepared by diluting a commercially available hydromorphone
hydrochloride injectable solution is stable in the PCA injectors stored
between 5°C and 35°C for 16 weeks. All hydromorphone solutions
evaluated after 8-week storage in PCA injectors exhibited >95% of their
original concentration. At 16 weeks, <10% loss of hydromorphone was
found. In addition, the hydromorphone solution remained sterile in the
PCA injectors over the 16-week period. This allows the preparation
of the PCA injectors in a large batch for later use in the treatment of
and/or risk of contamination.
Conclusion
This study demonstrated that hydromorphone in PCA injectors
prepared from commercially available formulation of hydromorphone
hydrochloride has acceptable chemical stability and sterility up to 16
weeks of storage under normal temperature conditions encountered in
clinical and storage settings. Based on these data, the practice of storing
the hydromorphone in PCA injectors for later use is acceptable from a
stability and sterility perspective.
Acknowledgments
The authors extend their gratitude to Dr. James J. Knittel, Philip
T. Cherian, and Assistant Dean Andrea L. Wall for their assistance in
completing this study.
References
1. Charlton E. The management of postoperative pain. Update Anaesthe-
sia 1997; 7: 1–7.

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 163
Peer Reviewed

2. Moulin DE, Johnson NG, Murray-Parsons N et al. Subcutaneous 21. Trissel LA. Handbook on Injectable Drugs. 15th ed. Bethesda, MD:
narcotic infusions for cancer pain: Treatment outcome and guidelines American Society of Health-System Pharmacists; 2009: 871.
for use. CMA J 1992; 146(6): 891–897. 22. Trissel LA, Xu QA, Pham L. Physical and chemical stability of hy-
3. Negro S, Reyes R, Azuara ML et al. Morphine, haloperidol and hyo- dromorphone hydrochloride 1.5- and 80-mg/mL packaged in plastic
scine N-butyl bromide combined in s.c. infusion solutions: Compat- syringes. IJPC 2002; 6(1): 74–76.
ibility and stability evaluation in terminal oncology patients. Int J 23. British Pharmacopeia. Vol I. London, UK: Stationery Office; 2009:
Pharm 2006; 307(2): 278–284. 1023–1024.
4. Eisenach JC, Grice SC, Dewan DM. Patient-controlled analgesia fol- 24. Trissel LA, Trusley C, Ben M et al. Physical and chemical stabil-
lowing cesarean section: A comparison with epidural and intramus- ity of palonosetron hydrochloride with five opiate agonists during
cular narcotics. Anesthesiology 1988; 68(3): 444–448. simulated Y-site administration. Am J Health Syst Pharm 2007; 64(11):
5. Albert JM, Talbott TM. Patient-controlled analgesia vs. conventional 1209–1213.
intramuscular analgesia following colon surgery. Dis Colon Rectum 25. British Pharmacopeia. Vol IV, Appendix XVI. London, UK: Stationery
1988; 31(2): 83–86. Office; 2009: A399–A403.
6. McGrath D, Thurston N, Wright D et al. Comparison of one tech-
nique of patient-controlled postoperative analgesia with intramuscu- Address correspondence to S. Kevin Li, PhD, College of Pharmacy, University of
lar meperidine. Pain 1989; 37(3): 265–270. Cincinnati, 3225 Eden Avenue, Cincinnati, OH 45267-0004. E-mail: Kevin.li@
7. Chumbley GM, Hall GM, Salmon P. Patient-controlled analgesia: an uc.edu
assessment by 200 patients. Anaesthesia 1998; 53(3): 216–221.
8. Johnston KR, Fudin J. Administration of buprenorphine by continu-
ous subcutaneous infusion: Three case reports with commentary. J
Pharm Care Pain & Sympt Control 1993; 1(4): 35–42.
9. Fraser DG. Intravenous morphine infusions for chronic pain. Ann
Internal Medicine 1980; 93(5): 781–782.
10. Portenoy RK. Continuous infusion of opioid drugs in the treatment
of cancer pain: Guidelines for use. J Pain Symptom Manage 1986; 1(4):
223–228.
11. Citron ML, Johnston-Early A, Fossieck BE et al. Safety and efficacy
of continuous intravenous morphine for severe cancer pain. Am J Med
1984; 77(2): 199–204.
12. Fudin J, Smith HS, Toledo-Binette CS et al. Use of continuous
ambulatory infusions of concentrated subcutaneous (s.q.) hydro-
morphone versus intravenous (i.v.) morphine: Cost implications for
palliative care. Am J Hosp Palliat Care 2000; 17(5): 347–353.
13. Hildebrand KR, Elsberry DE, Anderson VC. Stability and compat-
ibility of hydromorphone hydrochloride in an implantable infusion
system. J Pain Symptom Manage 2001; 22(6): 1042–1047.
14. Lawlor P, Turner K, Hanson J et al. Dose ratio between morphine
and hydromorphone in patients with cancer pain: A retrospective
study. Pain 1997; 72(1-2): 79–85.
15. Mercadante S. Opioid rotation for cancer pain: Rationale and clinical
aspects. Cancer 1999; 86(9): 1856–1866.
16. Bruera E, Pereira J, Watanabe S et al. Opioid rotation in patients
with cancer pain. A retrospective comparison of dose ratios between
methadone, hydromorphone and morphine. Cancer 1996; 78(4):
852–857.
17. Golembiewski JA. Morphine and hydromorphone for postoperative
analgesia: Focus on safety. J Perianesth Nurs 2003; 18(2): 120–122.
18. Sarhill N, Walsh D, Nelson KA. Hydromorphone: Pharmacology and
clinical applications in cancer patients. Support Care Cancer 2001; 9(2):
84–96.
19. Foley KM. The treatment of cancer pain. N Engl J Med 1985; 313(2):
84–95.
20. Deer TR, Krames ES, Hassenbusch SJ et al. Polyanalgesic Consensus
Conference 2007: Recommendations for the management of pain by
intrathecal (intraspinal) drug delivery: Report of an interdisciplinary
expert panel. Neuromodulation 2007; 10(4): 300–328.

International Journal of Pharmaceutical Compounding www.ijpc.com

164 Vol. 14 No. 2 | March/April 2010

Menopausal Women's Access Path to
Bioidentical Hormone Replacement
Therapy: An Exploratory Study
Doris Moro, BHA, MRT(MR)
Ryerson University
Toronto, Ontario, Canada
Wendy Young, PhD
School of Nursing and Faculty of Medicine
Memorial University
St. John’s, Newfoundland and Labrador,
Canada
Richard Stein, BscPhm, FACA
The Medicine Shoppe Pharmacy
Toronto, Ontario, Canada
Winston Isaac, PhD
School of Health Services Management
Ryerson University
Toronto, Ontario, Canada
Deborah Goodman, PhD
Factor-Inwentash Faculty of Social Work
University of Toronto
Toronto, Ontario, Canada
Introduction
Physicians and other specialists in meno-
pausal health have been encouraged to discuss
options regarding hormone replacement
therapy (HRT) with patients.1-2 Menopause is
defined as cessation of menstruation for one
year usually occurring between the ages of 45
and 55.3 Replacement of estrogen, progester-
one, and testosterone, referred to as hormone
replacement therapy (HRT), is a common
treatment for symptoms associated with meno-
pause. The available HRT options are conven-
tional hormone replacement therapy (CHRT;
synthetic hormone replacement)4 and bioiden-
tical hormone replacement therapy (BHRT).
CHRT was developed in the 1940s to solve the
problem that bioidentical hormones degraded
rapidly.5 After development, CHRT was tested,
www.ijpc.com
Peer Reviewed
Abstract
The objective of this exploratory qualitative study was to describe (1) the
key factors affecting women’s initial decision to explore the use of bioi-
dentical hormones, (2) where women gather their information on bioi-
dentical hormones, (3) the enablers and barriers to obtaining bioidentical
hormones, and (4) how to improve the bioidentical hormone replacement
therapy access path.The study was conducted in a compounding pharmacy
located in a large urban area in southern Ontario, Canada. The participants
included four postmenopausal women between the ages of 46 and 72
who self-identified as users of bioidentical hormone replacement therapy
and with comprehensive provincial healthcare coverage. Participants were
recruited at a compounding pharmacy with the use of tri-fold brochures,
tear-sheets, and posters. The women participated in an audio-taped mini
focus group. Discussion was guided by six open-ended questions. Verba-
tim quotes were analyzed using an affinity diagram. Participants identified
three key factors related to their initial decision: (1) symptoms unalleviated
by synthetic hormone replacement therapy, (2) side effects from synthetic
hormone replacement therapy, and (3) personal preference. They obtained
information and support from many sources, including: family/friends,
publications, and specialists in menopausal health. Once participants had
made a decision, they obtained a prescription and accessed bioidentical
hormone replacement therapy at a compounding pharmacy. Knowledge-
able primary care physicians and compounding pharmacists were seen as
enablers. Lack of support/information and costs were identified as barri-
ers. Improvements to bioidentical hormone replacement therapy access
path were suggested. The results of this study suggest that there may be
value in implementing strategies to further encourage family physicians
and other specialists in menopausal health to discuss options regarding
hormone replacement therapy with patients. For example, the preparation
and distribution of updated consumer decision aids that summarize the
evidence on the options regarding hormone replacement therapy, includ-
ing bioidentical hormone replacement therapy, could be considered.
approved by the U.S. Food and Drug Adminis- that provide individualized custom prepara-
tration (FDA), and then prescribed to control tions for patients.6
menopausal symptoms. BHRT (estradiol, The scientific evidence related to the
estrone, estriol, progesterone, and testosterone) impact of CHRT and BHRT on patient out-
was first made available in the 1930s. BHRT comes is inconsistent. In the 1970s, the results
is prescribed by a physician and prepared of nonexperimental studies led investigators
by a “compounding pharmacy.” In Canada, to conclude that CHRT was associated with a
compounding pharmacies are provincially decreased risk of bone fracture.7 In the 1980s,
regulated and employ professional pharmacists CHRT was reported to be associated with a
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 165
Peer Reviewed
decreased risk of cardiovascular disease.7 Re-
cently the results of a very large randomized
trial known as the Women's Health Initia-
tive (WHI) strongly suggested that there was
an increased risk of stroke (41%), coronary
disease (29%), and breast cancer (26%) associ-
ated with long-term use of oral CHRT.8 The
release of the WHI results was associated with
a 38% decrease of HRT prescriptions and a
74% decrease in prescriptions for Premarin
and Provera (synthetic CHRT) in the U.S.9
The results from the WHI randomized trial
has led to a reported increase in the number
of women interested in learning about BHRT.3
Adams and Cannell10 found that women sur-
veyed in a compounding pharmacy stated that
“compared with standard hormones, natural
hormones are safer, cause fewer side effects,
and are equally or more effective for symptom
management.” Yet, the scientific evidence to
support women’s beliefs about the efficacy
of BHRT is weak.11-12 No large randomized
trials (RCT) of BHRT have yet been released.
Researchers are currently recruiting patients
for a study to determine if it will be feasible
to conduct an RCT comparing CHRT and
BHRT.13
Canadian menopause guidelines released in
2006 recommend that specialists in menopaus-
al health provide their patients “with advice,
encouragement and support, and trusted edu-
cational resources ….”1 However, information
on the uptake of the Canadian 2006 meno-
pause guidelines for women who have made
the decision to choose BHRT option is lacking.
Our exploratory study addresses a gap in the
BHRT literature related to decision making by
women interested in an alternative to CHRT.
Our research was designed to achieve the fol-
lowing research objectives:
1. Describe the key factors affecting women’s
initial decision to access BHRT.
2. Explore where women gather information
and support.
3. Explore the enablers and barriers for
women on the access path to BHRT.
4. Describe possible improvements to the ac-
cess path.
Ethics approval for the study was received
from Ryerson University.
Method
The design was an exploratory qualitative
study using a mini focus group. The setting
was a single compounding pharmacy that
International Journal of Pharmaceutical Compounding
166 Vol. 14 No. 2 | March/April 2010
was located in a large urban area in southern
Ontario, Canada. The participants included
four postmenopausal women between the
ages of 46 and 72 who self-identified as users
of BHRT and with comprehensive provincial
healthcare coverage. Participants were re-
cruited at a compounding pharmacy with the
use of tri-fold brochures, tear-sheets, and post-
ers. The participants provided written consent
(the Consent to Focus Group Participation
form can be viewed at www.ijpc.com) and
then participated in an audio-taped mini focus
group. The principal investigator facilitated a
two-hour discussion on barriers and enablers.
Discussion was guided by six open-ended
questions (Figure: Focus Group Questions).
The taped discussion was transcribed by
a professional transcriptionist. The principal
investigator (DM) transferred the participants’
comments to standard labels directly from
the transcript which was then affixed to 3 by 3
adhesive notes. An expert group of health pro-
fessionals then prepared an affinity diagram to
depict the access path by sorting the comments
displayed on the labels into categories/themes.
An affinity diagram is a technique used for
organizing large amounts of verbal information
into natural relationships. Each expert main-
tained silence throughout the sorting of com-
ments into categories/themes. The analysis
was complete when the card movement ceased
and consensus was reached by all.
Findings
The access path to BHRT based on the
categories identified by the experts is visually
displayed in this article. The experts identified
five steps on the path:
1. Make an initial decision to obtain informa-
tion on BHRT
2. Obtain information and support
3. Make an informed decision
4. Obtain a prescription
5. Purchase BHRT at compounding
pharmacies
As can be seen from the visual display,
the path reported by the participants was not
linear. The women reported that once the
initial decision was made, then information
was sought from friends, and/or books/web-
sites and/or from healthcare professionals. The
bi-directional arrows on the path indicate that
women reported that the access path could
include several visits to many healthcare pro-
fessionals, and consultations with additional
sources of information. In addition, enablers
and barriers were encountered at every step
along the access path.
Key Factors
Affecting Women’s
Initial Decision to
Access BHRT
At the top of the path are the three key
factors that affected women’s initial decision
to use BHRT: (1) unalleviated menopausal
symptoms, (2) side effects from synthetic HRT,
and (3) personal preference. Unalleviated
menopausal symptoms included: depression,
night sweats, insomnia, or mood swings. Par-
ticipants stated:
• “My mood swings were unbelievable with-
out BHRT.”
• “I felt like I was fighting depression.
Couldn’t cope with migraines, throwing up,
I had to go to bed.”
• “I went on antidepressants for insomnia.”
Quotes related to the side effects of syn-
thetic HRT assigned to this category included:
• “I couldn’t take synthetic. Even though they
stopped the hot flashes and other symp-
toms, it gave me eye pain…all around my
eyes and I tried every synthetic.”
• “Heard too many negative things about
HRT.”
Finally quotes related to personal prefer-
ences assigned to this category included:
• “I was sent home with synthetic HRT after
they took my ovaries out and never opened
the bottle.”
• “I take BHRT because they are natural and
I’m into natural remedies...I don’t believe in
synthetic HRT.”
• ”I don’t take synthetics, I had absolutely
no problem with BHRT and I’m a 72-year
old.”
Where Women Gather
Information and
Support
Women gathered information and support
from many sources including: family/friends,
books/websites, and healthcare profession-
als. A book mentioned by participants was
Suzanne Somers’ Ageless: The Naked Truth About
www.ijpc.com
 Peer Reviewed

Bioidentical Hormone Replacement Therapy Access Path Bioidentical Hormones. Quotes assigned to this
category by the experts included:
Factors Affecting Decision • “My husband brought all these brochures
and books home.”
• “I used books, wellness magazines and the
Internet for information...[and] finding
the compounding pharmacy that was very
knowledgeable.”
• “The compound pharmacist took time to
explain and discussed what I need... I read
the brochures handed out by the com-
pounding pharmacy.”
Unalleviated Symptoms Side Effects • “My pharmacist’s assistant told me about
BHRT and gave me a doctor who prescribes
it.”
• “I trust my gynecologist, she is younger
[and] really up on BHRT. She said, ‘I’d pre-
scribe this for my own mother... Information
makes me feel a lot better.’”

Enablers and
Personal Preference Barriers for Women
on the Access Path to
BHRT
Participants identified enablers and barriers
to obtaining information, obtaining a prescrip-
tion, and purchasing BHRT.

Obtaining
Information
Quality of available information was
reported by participants as a barrier to making
>

an informed decision. The Internet was noted

Obtain Information and Support
>
as a confusing medium from which to obtain
information due to the wide range of quality
in the information provided. The participants
>

>
>

commented:
Friends > > Books/Websites > > Health Care Professionals
• “This [BHRT information] should be on a
website if you want information. But some-
times the web is a dangerous place to go for
information.”
>

>

Make an Informed Decision Barriers/Enablers The attitude of the healthcare professional

was identified by focus group participants as
both the key enabler and the key barrier on
the access path identified by participants. The
>

healthcare professional was enabling if that

>
Obtain Prescription individual was supportive/trustworthy and
provided an explanation and ample informa-
tion to satisfy the patient’s questions. For
example, a participant remarked:
>

Purchase BHRT at Compounding Pharmacy > • “She’s [the gynecologist] marvellous, she
takes the time to sit down and explain.”

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 167
Peer Reviewed
The healthcare professional was identified
by participants as a barrier if that individual
lacked knowledge with respect to BHRT. The
women felt that some physicians did not listen
to their needs; that some physicians lacked the
knowledge to satisfactorily advise women on
alternatives to synthetic hormones; and some
doctors made unilateral decisions favoring
synthetic HRT without consulting the patient.
Physician’s reluctance to support woman’s
request for BHRT were expressed as:
• “My family doctor should have referred
me...she didn’t believe in bioidentical hor-
mones. I had to leave my doctor of twenty
years.”
• “We need more open-minded doctors.”
• “Doctors make unilateral decision towards
synthetics.”
Obtaining a
Prescription
Participants reported that once they had
made an informed decision to access BHRT,
they then encountered enablers and barriers
in obtaining a prescription. If the healthcare
provider was a “prescribing physician” then
access was enabled. The barriers identified
in this category were: struggle to find these
prescribing physicians; very few of these
prescribing physicians; long waits to see
prescribing physicians; and the personal costs
associated with accessing these physicians.
• “It was a struggle to find a prescribing phy-
sician and when you did there were long
waits to see these doctors.”
• “I’ve never been able to find a doctor
except the one I emailed back and forth on
the Internet in the States. He was the only
one that explained I was not getting the
right balance of estrogen and progester-
one.”
Purchasing BHRT
The last step on the access path, catego-
rized by the experts as the purchase of BHRT,
had additional enablers and barriers in the
purchase of BHRT. The “compounding phar-
macist” was identified as the key enabler. The
“cost” of bioidentical hormone therapies was
identified as the key barrier. Some drug plans
do not compensate subscribers for bioidenti-
cal hormones, for saliva testing of hormones,
and the compounded formulas. Participants
stated:
International Journal of Pharmaceutical Compounding
168 Vol. 14 No. 2 | March/April 2010
• “I can’t afford the two to five hundred dol-
lars required to go see a BHRT prescribing
physician in a private clinic.”
• “The price of hormone saliva testing is too
high.”
Possible
Improvements to the
Access Path
In response to the focus group question on
possible suggestions for improving the path-
way, participants made the following recom-
mendations:
• Continuing education for physicians to pro-
mote understanding of the available options
in hormone replacement therapy
• A comprehensive website that objectively
detailed risks and benefits of both synthetic
and bioidentical hormones
• The provision of regular seminars for
menopausal women
• Policy changes to allow other health profes-
sionals to prescribe BHRT
• Establish women-only clinics, where the in-
formation on all forms of hormone therapy
is organized and readily available
Discussion
Principal Findings
The results of this study, conducted after
the 2006 release of the Canadian menopause
guidelines, suggest that women who are trying
to access bioidentical hormones are motivated
by three key factors: (1) the adverse symptoms
of menopause, (2) the concerns with side
effects of conventional synthetic hormone
therapy, and (3) personal preferences. They
obtained information and support from many
sources including: family/friends, publica-
tions (books, brochures, wellness newsletters,
websites), and specialists in menopausal health.
Once participants had made a decision, they
obtained a prescription and accessed BHRT
at a compounding pharmacy. Knowledgeable
primary care physicians and compounding
pharmacists were seen as enablers. Lack of
support/information and costs were identified
as barriers. Participants suggested continuing
education for physicians to promote under-
standing of the available options in HRT.
Strengths and Weaknesses of the
Study
The strength of this study is that it ac-
quaints readers with some beginning informa-
tion of women’s perceptions of the BHRT
access path, two years after the release of the
2006 menopause guidelines. In 1998, Blake14
remarked in an editorial in the Canadian Fam-
ily Physician “We need to support patients'
attempts to sort through the quagmire of infor-
mation.” Ten years after the release of this
editorial, participants in our study highlighted
the opportunities for family physicians to pro-
vide women with reliable information on HRT
options. The small sample size is a limitation.
The focus group participant’s social economic
status (SES) was middle class, therefore, limit-
ing the results to women in this category only.
An unknown was how a disadvantaged women
or low SES status would affect the results.
Cultural diversity of the focus group was also
limited to subjects limited to one small geo-
graphic area. Nevertheless, this study is a good
beginning with regard to identifying issues
that could be used as a basis for constructing
a further study on the impact of the release of
the menopause guidelines. The study draws
attention to an important issue for family
physicians—menopause and BHRT.
Strengths and Weaknesses in
Relation to Other Studies
As our study is the first to look at women’s
perceptions post-guideline release, it is not
possible to compare our findings to other stud-
ies. Nevertheless, our main findings are similar
to those reported in earlier studies. Seidl and
Stewart,15 in a qualitative study conducted in
Toronto, Ontario, Canada, identified personal
control over health as the key factor affecting
women's initial decision to explore the use
of BHRT. Ma et al16 concluded that women
residing in the U.S. who participated in a
national survey reported that women obtained
information from many lay sources and that
the participants were not confident that their
physicians were knowledgeable about HRT
options. Seidl and Stewart15 identified knowl-
edgeable primary care physicians as enablers
and lack of support/information and costs
were identified as barriers. Finally, the educa-
tional interventions suggested by our partici-
pants are similar to those recently examined by
Le´gare´ et al; their trial reported that a patient
decision aid regarding the use of natural health
products at menopause increased knowledge
of available options.17
Implications for Family Physicians
These results suggest that our participants
are looking to family physicians to play a
www.ijpc.com

key role in providing reliable information
to women about menopause and treatment
options. Women want to manage their signs
and symptoms of menopause in a way that is
acceptable to their beliefs about their health-
care delivery and minimize risks of other
harm to their health that is associated with
synthetic therapy. Family physicians in busy
practices may be increasingly challenged to
find ways to help women in the decision-
making process.
Future Directions for Research
Further study is required to investigate the
impact of the Canadian Consensus statement
on menopause factors. Our exploratory study
highlights the importance of evaluating the
dissemination and uptake of these types of
initiatives to ensure that the Consensus Con-
ference on Menopause is achieving the goals
for which they were created. Our preliminary
study will help to raise some questions that
can be a platform upon which to build further
studies.
Conclusion
The results of this study suggest that there
may be value in implementing strategies
to further encourage family physicians and
other specialists in menopausal health to
discuss options regarding HRT with patients.
For example, the preparation and distribution
of updated consumer decision aids that sum-
marize the evidence on the options regarding
HRT, including BHRT, could be considered.
References
1. Canadian Consensus Conference on
Menopause. Canadian Consensus Confer-
ence on Menopause, 2006 update. No. 171.
JOGC 2006; 28(2): S1.
2. Executive Committee of the International
Menopause Society. Guidelines for hor-
mone treatment of women in the meno-
pausal transition and beyond: Position
Statement by the Executive Committee
of the International Menopause Society.
Maturitas 2005; 15(1): 15–20.
3. Cirigliano M. Bioidentical hormone
therapy: A review of the evidence. J Wom-
ens Health 2007; 16(5): 600–631.
4. La Valleur J. Counseling the perimeno-
pausal woman. Obstet Gynecol Clin North Am
2002; 29(3): 541–553.
5. Francisco L. Is bio-identical hormone
therapy fact or fairy tale? Nurse Pract 2003;
28(7 Pt 1): 39–44.
www.ijpc.com
Peer Reviewed
6. Watt PJ, Hughes RB, Rettew LB et al. A
holistic programmatic approach to natural
hormone replacement. Fam Community
Health 2003; 26(1): 53–63.
7. MacLennan AH. HRT: A reappraisal of
the risks and benefits. Med J Aust 2007;
186(12): 643–646.
8. Ness J, Aronow WS, Newkirk E et al.
Use of hormone replacement therapy by
postmenopausal women after publication
of the Women’s Health Initiative Trial.
J Gerontol A Biol Sci Med Sci 2005; 60(4):
460–462.
9. Hersh AL, Stefanick ML, Stafford RS.
National use of postmenopausal hormone
therapy: Annual trends and response to
recent evidence. JAMA 2004; 291(1): 47.
10. Adams C, Cannell S. Women’s beliefs
about “natural” hormones and natural
hormone replacement therapy. Menopause
2001; 8(6): 433–440.
11. Boothby LA, Doering PL, Kipersztok S.
Bioidentical hormone therapy: A review.
Menopause 2004; 11(3): 356–367.
12. Kuehn BM. FDA warns claims for
pharmacy-made “bio-identical” hormones
are misleading. JAMA 2008; 299(5): 512.
13. University of Kansas. Bioidentical ‘natural’
hormone evaluation in early menopause.
Identifier NCT00302731. [ClinicalTri-
als.gov Website.] September 14, 2009.
Available at: http://clinicaltrials.gov/ct2/
show/record/NCT00302731?intr=”Medr
oxyprogesterone+17-Acetate”&rank=17.
Accessed July 24, 2008.
14. Blake J. Hormone replacement. Can Fam
Physician 1998; 44: 1205–1206, 1216–1217.
15. Seidl MM, Stewart DE. Alternative treat-
ments for menopausal symptoms. Qualita-
tive study of women’s experiences. Can Fam
Physician 1998; 44: 1271–1276.
16. Ma J, Drieling R, Stafford RS. US women
desire greater professional guidance on
hormone and alternative therapies for
menopause symptom management. Meno-
pause 2006; 13(3): 506–516.
17. Légaré F, Dodin S, Stacey D et al. Patient
decision aid on natural health products
for menopausal symptoms: Randomized
controlled trial. Menopause Int 2008; 14(3):
105.
Address correspondence to Wendy Young, PhD,
School of Nursing and Faculty of Medicine, Memo-
rial University, 300 Prince Philip Drive St. John’s,
Newfoundland and Labrador, A1B 3V6. E-mail:
youngw@mum.ca
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 169
Peer Reviewed

Figure. Focus Group Questions.

Health Services Management

1. Write down three things that worked well when you were looking for bioidentical hormones. Write
down at least one area that could be improved.

2. Why did you choose bioidentical hormones?
• What factors made you switch or use these hormones?
• Did you ever use synthetic hormones and why?
• Who or what was influential in leading you to bioidentical hormones?

3. What are your impressions of information received on bioidentical hormones?

• Ease of obtaining information
• Credibility of information
• Sources of information
• Comprehension of material

4. Were there any problems with access to physician’s prescribing bioidentical hormones?
• Do you have any suggestions for improving this access?
• How can physicians and other health care providers ensure that patients receive effective
information?

5. What are your impressions of the emotional support given by friends, family and health
professionals?
• Pharmacists
• Medical specialists, Nurses
• Alternative medicine. I.e. Naturopaths, Homeopath’s

6. Imagine we had a women searching for bioidentical hormones, what would be her ideal journey?
• What would make her journey easier?
• Do you have any suggestions for pharmacies, physicians or other medical professionals in
improving the pathway to bioidentical hormones?

Thank you for participating in this focus group. Your participation will lead to a better understanding
of the issues that women face on their path to choosing bioidentical hormones. We have a $25 gift
card to Tim Horton’s to thank you for you time and interest in this project

International Journal of Pharmaceutical Compounding www.ijpc.com

170 Vol. 14 No. 2 | March/April 2010

Low Dose Naltrexone: Side Effects and
Efficacy in Gastrointestinal Disorders
Jennifer Ploesser
St. Louis College of Pharmacy
St. Louis, Missouri
Leonard B. Weinstock, MD
Washington University School of Medicine
Specialists in Gastroenterology, LLC
St. Louis, Missouri
Erin Thomas, PharmD
Trilogy Healthcare, LLC
St. Louis, Missouri
Introduction
Naltrexone is U.S. Food and Drug Adminis-
tration (FDA)-approved for relapse prevention
of alcohol dependence, and it plays a role in
relapse prevention of narcotic abuse.1-2 The
dose of oral naltrexone for these purposes is 50
mg daily.
Use of low dose naltrexone (LDN) (1.75 to
4.5 mg daily) has been advocated on the Inter-
net for a variety of medical problems.3 Only
a few articles on LDN or ultra-LDN have
been published in peer reviewed journals.4-6 A
recent review elucidated the potential mode
of action including immune-modulation and
anti-inflammatory processes.7 Manipulation
of opioid receptors has potential application
in gastrointestinal disorders. Opioid neurons
exhibit tonic restraint on intestinal motility;
opioid antagonists stimulate peristalsis and
increase transit. Anti-inflammatory effects are
also desirable for both inflammatory bowel
disease and irritable bowel syndrome (IBS).
Naltrexone is a water soluble compound
which crosses the blood brain barrier, and this
increases the potential for neurologic side
effects. Reported adverse effects of standard
dose naltrexone include anxiety, nervous-
ness, confusion, drowsiness, hallucinations,
skin crawling, blurred vision, muscle or joint
pain, vomiting, diarrhea, stomach pain, liver
disease, and skin rash. There were no signifi-
cant adverse reactions using ultra-LDN (0.5
mg) in one study.4 Recent FDA approval of
subcutaneously injected methylated formula-
www.ijpc.com
Peer Reviewed
Abstract
Use of low dose naltrexone has been advocated for a variety of medical
problems. Only a few articles published in peer reviewed journals have
documented side effects of low dose naltrexone. The purpose of this study
was to determine the frequency of adverse effects of low dose naltrexone
in patients who have been treated for a variety of gastrointestinal disor-
ders. The secondary purpose was to determine global efficacy in a ret-
rospective survey. Patients (206) from a single gastroenterologist’s clini-
cal practice who had been prescribed naltrexone were mailed a survey to
evaluate the side effects and efficacy of naltrexone. Patients had either
irritable bowel syndrome without evidence for small intestinal bacterial
overgrowth, irritable bowel syndrome with evidence of small intestinal
bacterial overgrowth, chronic idiopathic constipation, or inflammatory
bowel disease. Patients with diarrhea were given 2.5 mg daily, constipa-
tion 2.5 mg twice daily, and inflammatory bowel disease 4.5 mg daily. In
the patients who returned the survey, 47/121 (38.8%) had no side effects.
Of the 74/121 (61.2%) patients who had side effects, 58 had one or more
neurological complaints, and 32 had one or more gastrointestinal side ef-
fects. In the patients with side effects, 24/74 (32.4%) had short lived symp-
toms. Low dose naltrexone was terminated owing to side effects in 20/74
patients (27.0%). In 13 patients with idiopathic irritable bowel syndrome, 2
were markedly improved, 5 were moderately improved, 2 were unchanged,
and 3 were markedly worse. In 85 patients with irritable bowel syndrome-
small intestinal bacterial overgrowth, 15 were markedly improved, 32
were moderately improved, 11 were mildly improved, 23 were unchanged,
3 were moderately worse, and 1 was markedly worse. In 12 patients with
chronic constipation, 7 were markedly improved, 1 was moderately im-
proved, 3 were mildly improved, and 1 was unchanged. Two of 8 patients
with inflammatory bowel disease were markedly improved, 1 was moder-
ately improved, 1 was mildly improved, and 4 were unchanged. Low dose
naltrexone frequently has side effects but in most is tolerable. It appears
to be helpful for a number of patients with gastrointestinal disorders.
tion, methylnaltrexone (Relistor), allows for purpose was to determine global efficacy in a
safe use of this compound in patients who are retrospective survey.
on narcotics. Methylnaltrexone is effective
for opioid-induced constipation by reversing
peripheral opioid receptors.8 Material and
At this point in time, methylnaltrexone is Methods
not available in oral formulation and thus the LDN was compounded in 2.5-mg and
role of oral LDN needs to be further defined. 4.5-mg capsules. The source of naltrexone was
The purpose of this study was to determine Spectrum Chemical Manufacturing Corpora-
the frequency of adverse effects of LDN in tion. Compounding began by first calculating
patients who have been treated for a variety of the ingredient filling constants. Ingredients
gastrointestinal (GI) disorders. The secondary other than naltrexone included microcrystal-
International Journal of Pharmaceutical Compounding
Vol. 14 No. 2 | March/April 2010 171
Peer Reviewed
line cellulose as a filler and some food color
powder to assure proper blending of powders.
Formulas for batches of 100 and 300 capsules
were calculated using the filling constants;
and powders were mixed using an electronic
mortar and pestle. The final powder mixture
was then placed into empty size #3 gelatin
capsules which were locked into capsule ma-
chines. Once the capsules were appropriately
packed, the capsule tops were locked onto
the capsule bottoms.
Patients from a single gastroenterologist’s
clinical practice who had been prescribed
naltrexone in a two-year period were mailed
a letter asking if they would participate in
a survey to evaluate the side effects and ef-
ficacy of naltrexone. If they did not return
the survey they were called once to remind
them to fill out the survey. The majority of
the patients had received prescriptions in the
previous six months.
Patients (206) with the following GI
conditions were given prescriptions for LDN:
IBS without evidence for small intestinal
bacterial overgrowth (SIBO) (i.e., patients
with a normal lactulose breath test), IBS with
evidence of SIBO (using naltrexone as a sec-
ond phase of treatment in efforts to improve
motility and reduce inflammation), chronic
idiopathic constipation, and patients with
inflammatory bowel disease. Patients with di-
arrhea were given 2.5 mg daily, constipation
2.5 mg twice daily, and inflammatory bowel
disease 4.5 mg daily.
In the survey they were asked about the
duration and dose of naltrexone adminis-
tered. They were asked if they had any of
the following side effects: trouble sleep-
ing, nightmares or vivid dreams, jitteriness,
nervousness, dizziness, headache, drowsi-
ness, anxiety, vomiting, decrease in appetite,
diarrhea, stomach pain, muscle pain, nausea,
or other symptoms. They were asked if the
side effects improved with continued use
of the naltrexone and if they had to stop
using naltrexone because of a side effect. If
they were no longer taking naltrexone, they
were asked what made them stop taking
it: condition improved, unacceptable side
effects, or the medicine did not work. They
were asked if their overall GI symptoms were
markedly improved, moderately improved,
slightly improved, unchanged, slightly worse,
moderately worse, or markedly worse. If they
had SIBO, they were asked if they needed to
take another antibiotic since being placed on
naltrexone.
International Journal of Pharmaceutical Compounding
172 Vol. 14 No. 2 | March/April 2010
Results
Surveys were returned by 121/206 (58.7%)
of the patients. The mean age (±1 standard
deviation) was 53.0 ±16.8. Of these 92 women
and 29 men, 85 had IBS with SIBO, 14 had
idiopathic IBS, 12 had slow transit chronic
constipation, 8 had inflammatory bowel disease
(Crohn’s disease in 4 and ulcerative colitis in
4), and 2 had small bowel pseudoobstruction.
The daily dose of naltrexone was 2.5 mg in 67,
5.0 mg in 46, and 4.5 mg in 8 patients.
In the patients who returned the survey,
47/121 (38.8%) had no side effects. Of the
74/121 (61.2%) patients who had side effects,
58 had one or more neurological complaints,
and 32 had one or more GI side effects. The
profile of the side effects is shown in the ac-
companying Table. In the patients with side ef-
fects, 24/74 (32.4%) had short-lived symptoms.
In twenty of the 74 patients (27.0%), naltrex-
one was terminated owing to side effects. The
rest of the patients were able to tolerate the
side effects. The frequency of side effects for
the group treated with 2.5 mg compared with
the group treated with 5.0 mg daily differed in
three symptoms, respectively:
1. Anxiety (11.9 vs. 21.7%)
2. Muscle pain (4.5 vs. 15.2%)
3. Diarrhea (6.0 vs. 13.0%)
The efficacy of naltrexone was determined a
global assessment of overall clinical improve-
ment:
• Markedly improved
• Moderately improved
• Mildly improved
• Unchanged
• Mildly worse
• Moderately worse
• Markedly worse
Naltrexone was used to supplement stable
existing therapy in IBD patients or act as sole
treatment in the cases of IBS-SIBO and idio-
pathic IBS. Patients with chronic constipation
were treated with LDN alone or as an adjunct
to other partially effective medications.
Of the 13 patients with idiopathic IBS (3
with diarrhea, 5 with constipation, and 5 with
alternating bowel habits), the results were:
• 2 (15.3%) were markedly improved
• 5 (38.5%) were moderately improved
• 2 (15.3%) were unchanged
• 3 (23.1%) were markedly worse
Of the 3 that were worse, the results were:
• 1 had IBS-constipation
• 2 had IBS-alternating bowel habits
The 85 patients with IBS-SIBO were
treated for a mean of 14.2 weeks (58 with 2.5
mg and 27 with 2.5 mg twice daily LDN), with
the following results:
• 15 (17.6%) were markedly improved
• 32 (37.6%) were moderately improved
• 11 (12.9%) were mildly improved
• 23 (27.0%) were unchanged
• 3 (3.5%) were moderately worse
• 1 (1.2%) were markedly worse
A second course of antibiotics were admin-
istered in 38% of these patients during the 14
weeks to retreat recurrent symptoms of SIBO.
LDN (2.5 mg twice daily) was administered
for a mean of 10.8 weeks in 12 patients with
chronic constipation. Of these patients, the
results were:
• 7 (58.3%) were markedly improved
• 1 (8.3%) was moderately improved
• 3 (25.0%) were mildly improved
• 1 (8.3%) was unchanged
Eight patients with inflammatory bowel
disease (4 Crohn’s and 4 ulcerative colitis)
were treated with 4.5 mg naltrexone daily for a
mean of 16.8 weeks, with the following results:
• Two were markedly improved
• 1 was moderately improved
• 1 was mildly improved
• 4 were unchanged
Two of those who stated they were un-
changed were in clinical remission prior to
starting naltrexone.
Discussion
The current study shows that side effects
of LDN occurred frequently (61%) and led
to cessation of the treatment in a quarter of
those with adverse effects. The retrospective
nature of the study and incomplete return of
the surveys would likely bias the frequency
to a higher number of adverse effects. There
are few studies that have evaluated side
effects of LDN. In 40 multiple sclerosis
patients treated with 3.0 mg naltrexone, 3
reported having trouble concentrating and 1
reported having fatigue.6 In 42 IBS patients
www.ijpc.com
 Peer Reviewed

Table. Side Effects of Low Dose Naltrexone in 121 Patients.

Neurological Side Effects Number of Participants with Side Effects Percentage of Participants with Side Effects
Anxiety 19 15.7
Drowsiness 14 11.6
Headache 14 11.6
Dizziness 13 10.7
Insomnia 10 8.3
Muscle pain 10 8.3
Vivid dreams 6 5.0
Mood change 4 3.3
Trouble concentrating 2 1.7

Gastrointestinal Side Effects

Nausea 15 12.4
Abdominal pain 14 11.6
Diarrhea 10 8.3
Anorexia 10 8.3

Other Side Effects

Rash 1 0.1
Hot flashes 1 0.1
Weight gain 1 0.1

treated with ultra-LDN (0.5 mg), no side
effects were reported.4
There is theoretic value to use of LDN in
GI disorders, but few articles have been pub-
lished. One study of 50 mg naltrexone to affect
GI motility failed to show efficacy in treat-
ment of constipation in IBS.9 In an open-label
study, 89% of 17 Crohn's disease exhibited
a response to LDN (4.5 mg daily), and 67%
achieved a remission (P <0.001).6 In another
open-label study, 42 IBS patients participated
and received ultra-LDN (0.5 mg daily).4
During treatment, the mean weekly number
of pain-free days increased from 0.5+/-1 to
1.25+/-2.14 (P = 0.011).
In the present study, the global responses to
LDN appeared to show promise in IBS, IBS-
SIBO, chronic constipation, and inflammatory
bowel disease. The nature of this study did not
allow for quantitative analysis. Retrospective
nature and incomplete data collection further
reduced the conclusions that can be reached.
Further study appears to be warranted to de-
termine the efficacy of LDN in GI diseases.
Acknowledgment
This study was approved by a human studies
committee (Sterling Institutional Review Board,
Georgia, Alabama).
Conclusion 6. Gironi M, Martinelli-Boneschi F, Sac-
LDN is not without potential for side erdote P et al. A pilot trial of low-dose
effects. Future use of methylnaltrexone may naltrexone in primary progressive multiple
be better tolerated since it does not cross the sclerosis. Mult Scler 2008; 14(8): 1076–1083.
blood brain barrier. 7. Brown N, Panksepp J. Low-dose naltrex-
one for disease prevention and quality of
life. Med Hypotheses 2009; 72(3): 333–337.
References 8. Thomas J, Karver S, Cooney GA et al.
1. Garbutt JC. The state of pharmacotherapy Methylnaltrexone for opioid-induced
for the treatment of alcohol dependence. J constipation in advanced illness. N Engl J
Med 2008; 358(22): 2332–2343.
Subst Abuse Treat 2009; 36(1): S15–S23.
9. Foxx-Orenstein AE, Camilleri M, Szarka
2. Adi Y, Juarez-Garcia A, Wang D et al.
LA et al. Does co-administration of a
Oral naltrexone as a treatment for relapse
non-selective opiate antagonist enhance
prevention in formerly opioid-dependent
acceleration of transit by a 5-HT4 agonist
drug users: A systematic review and
in constipation-predominant irritable
economic evaluation. Health Technol Assess
bowel syndrome? A randomized controlled
2007; 11(6): iii–iv, 1–85.
trial. Neurogastroenterol Motil 2007; 19(10):
3. [No author listed.] Low dose naltrexone.
821–830.
[Low Dose Naltrexone Website.] Decem-
ber 20, 2009. Available at: www.lowdosen- Address correspondence to Dr. L. Weinstock, 11525
altrexone.org. Accessed March 30, 2009. Olde Cabin Road, St. Louis, MO 63141. E-mail:
4. Kariv R, Tiomny E, Grenshpon R et al. lw@gidoctor.net
Low-dose naltrexone for the treatment of
irritable bowel syndrome: A pilot study.
Dig Dis Sci 2006; 51(12): 2128–2133.
5. Smith JP, Stock H, Bingaman S et al. Low-
dose naltrexone therapy improves active
Crohn's disease. Am J Gastroenterol 2007;
102(4): 820–828.

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 173
 Postscription
Is Being Involved in the Pharmacy
Student Preceptor Program Worth
the Effort?
Loyd V. Allen, Jr., PhD, RPh
International Journal of Pharmaceutical Compounding
Edmond, Oklahoma
The International Journal of Pharmaceutical Compounding (IJPC)
encourages compounding pharmacies to participate in the pharmacy
student preceptor programs of their local universities. Moreover, we
have published many articles in our journal, the International Journal of
Pharmaceutical Compounding, about the importance of this program and
have published several articles actually written by students of phar-
macy schools. We “practice what we preach,” as IJPC has invited many
pharmacy students to fulfill part of their rotation at our home office in
Photo of Dared Price. Dared served part of his
pharmacy student rotation at the offices/lab
of the International Journal of Pharmaceutical
Compounding, Edmond, Oklahoma.
International Journal of Pharmaceutical Compounding
174 Vol. 14 No. 2 | March/April 2010
Edmond, Oklahoma. These students were enrolled at The University of
Oklahoma College of Pharmacy (Oklahoma City and Tulsa campuses)
and Southwestern Oklahoma State University School of Pharmacy. Yes,
it took some of our time, especially mine, as anytime a student is pres-
ent, a registered pharmacist must be on hand the same as a professor of
pharmacy must be in the classroom with the students. Our participation
has not been without expense, but it was well worth the expense and our
time, and we feel certain it was educational for the students.
As seasoned pharmacists, we should be mentors to these students who
are close to becoming pharmacy graduates. Compounding pharmacy is
constantly under the microscope and our efforts to educate these new
pharmacists could possibly prevent them from making mistakes that
could result in a patient’s death; a mistake that could possibly end their
pharmaceutical career. Internship in an actual pharmacy setting broad-
ens the views of these young professionals in pharmacy practice, policy
issues, the superfluity of opportunities, and specialized careers in the
healthcare industry.1 As one practicing compounding pharmacist who
interned at a compounding pharmacy eloquently stated2:
While compounding should be the main focus of your
clinical pharmacy rotation, you have the opportunity to
teach your students so much more. Many of you are in a
unique position to teach your students skills that they may
never have the opportunity to learn elsewhere. Develop
a rotation that gives the student a well-rounded learning
experience that encompasses the art of compounding and
more. The rewards…priceless!
The remainder of this article was submitted by Mark Burger, a prac-
ticing compounding pharmacist in Windsor, California, about his intern-
ship while working at the U.S. Food and Drug Administration (FDA) as
part of his Masters Graduate program. We think the experience shared
by Mark is an excellent example of how valuable the internship program
is to the intern, the preceptor, and, in the long-run, the patients. The
scenario described by Mark is also a good example of a “life lesson” and
unusual results of a student’s internship.
References
1. Kirk LM. Golden ticket to the United States Pharmacopeial Conven-
tion’s veterinary internship. IJPC 2008; 12(5): 410–413.
2. Walkup KR. Developing and implementing a clinical pharmacy
rotation in a community compounding pharmacy. IJPC 2008; 12(3):
213–215.
Address correspondence to Loyd V. Allen, Jr., PhD, RPh, International Journal of
Pharmaceutical Compounding, Inc., 122 N. Bryant Avenue, Edmond, OK 73034.
E-mail: lallen@ijpc.com
www.ijpc.com
 Postscription

Mark Burger, PharmD paradoxically, it became difficult-to-impossible extravasation, unintentional intra-arterial

Health First! Pharmacy
Windsor, California
As part of my Masters Graduate program,
I worked for the FDA in Rockville, Maryland.
My assignment and thesis project was to gather
information about the Adverse Drug Event
Reporting (ADR) system and its effectiveness.
This was in 1975—pre-computer age.
My thesis/argument was that the FDA’s
ADR system was burdensome and was slow at
getting meaningful changes made on the package
insert, referred to as “labeling” by the FDA. As
part of my thesis, I wanted to present a test
case. I chose to discuss the terrible sequelae of
skin necrosis in newborns that were inadver-
tently given intra-arterial hydroxyzine/Vistaril,
a mistake that resulted in a number of children
losing parts of their scalp (at the time, most
newborns involved had scalp-vein access) and
adults losing skin and fingers. Years later, the
FDA finally changed the labeling of this drug
to “Intramuscular Use Only”; that same label-
ing is used today.
Part of the requirements to complete my
thesis was to look up the ADRs (historically),
document the actions that were taken, and
determine the time-line involved in making the
decision and actually effecting a change to the
labeling. This would be a part of my test case.
Another goal of my thesis was to show that a
regular review of current medical literature
(e.g., IJPC, Journal of the American Medical
Association, New England Journal of Medicine, Post-
graduate Medicine) to search for evidence (e.g.,
to locate the files that I needed to complete my
test case. By the end of my six-month intern-
ship, my efforts were completely useless. I was
naïve at the time because I thought everyone
would help me acquire the information to com-
plete my thesis. It soon became apparent that
my efforts were stepping on some very big toes.
As a postscript, I would like to add that the
scenario described above about intra-arterial
hydroxyzine/Vistaril is currently happening
with a similar pre-anesthetic/pre-operative
drug—promethazine hydrochloride—with its
inadvertent injection into an artery, which, in
a likewise fashion, is getting its own black box
warning. According to FDA Medwatch in an
alert posted on September 16, 2009 for health-
care professionals, it was stated:1
Intravenous administration of prometh-
azine can cause severe tissue injury, in-
cluding gangrene, requiring fasciotomy,
skin graft, and/or amputation….Severe
tissue injury can occur from perivascular
injection, and intraneuronal or perineu-
ronal infiltration. The preferred route of
administration is deep intramuscular in-
jection. Subcutaneous and intra-arterial
injections are contraindicated.
It would be interesting to see how many
reports, over what period of time were required
to bring us to this latest warning.
Reference
1. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. Recalls and
Safety Alerts: Boxed Warning about Tissue Injury with
IV Promethazine. [U.S. Food and Drug Adminis-
tration Website.] December 2009. Available at:
www.fda.gov/Safety/MedWatch/SafetyInforma-
tion/SafetyAlertsforHumanMedicalProducts/
ucm182500.htm. Accessed February 10, 2010.
Address correspondence to Mark Burger, PharmD,
Health First! Pharmacy, 9070 Windsor Road, Wind-
sor, CA 95492. E-mail: mark@healthfirstphar-
macy.net
FDA License No. 103
USDA License No. 629

case reports, letters to the editor) would more

effectively reveal any current problem with a
drug and was an inexpensive way to locate the
information needed to initiate labeling changes.
These types of anecdotal reports can be very
efficient: singularly, the likelihood of reporting
is low, but collectively, the chances are high
that a prescriber or pharmacist would write a
similar case report or letter, thereby gathering
momentum for change. It was also a quicker
process than relying on the “generosity of
spirit” of health professionals to take the time
(and risk) to fill out and submit an ADR. The
process of obtaining good data was more dif-
ficult because of the poor quality of the ADRs
that were submitted.
While at the FDA, I had an excellent super-
visor who took me under his wing. He was a
physician that headed up the Psychopharma-
cology Division in the Bureau of Drugs. How-
ever, once the “word” got out about my “thesis,”

www.ijpc.com International Journal of Pharmaceutical Compounding

Vol. 14 No. 2 | March/April 2010 175
 Index of Advertisers
March | April | 2010

IJPC Subscription and

Ordering Information Advertisers:
The International Journal of Pharmaceutical Compounding (IJPC), ISSN 91 AirClean Systems
No. 1092-4221, is published 6 times per year by International Journal of 800-849-0472; www.aircleansystems.com
Pharmaceutical Compounding, Inc. (IJPC), 122 N. Bryant Avenue, Edmond
OK 73034, USA. 175 Allergy Laboratories, Inc.
800-654-3971; www.allergylabs.com

Annual Subscription Rates 101 Analytical Research Laboratories

(All rates in US dollars) 800-393-1595; www.arlok.com
Standard Institutional APhA
Rate Rate Discounted Rate 147 Associates of Cape Cod Inc.
888-395-2221; www.acciusa.com
US & Canada $175 $200 $140
All Other $225 $250 $180 111 B&B Pharmaceuticals, Inc.
Destinations 800-499-3100; www.bandbharmaceuticals.com

*Electronic $175 $200 $140 145 Charles River

Copy Only 877-CRIVER-1; www.criver.com
Standard Rate: Community/independent pharmacists, retail chain pharma-
cists, research pharmacists, educators, and all other individuals 143 DynaLabs
888-396-2522; www.dynalabs.us
Institutional Rate: Hospital, industry, libraries, and universities
APhA Discounted Rate: Individuals with active membership in the American 127 Eagle Analytical Services
Pharmacists Association (APhA) 800-745-8916; www.eagleanalytical.com
*Destination outside US and Canada Only
97 EPS, Inc.
Back issues are available 800-523-8966; www.medidose.com
$35 per back issue. Call 800-757-4572 or 405-330-0094 to order issues or sub- OBC Gallipot, Inc.
scriptions or visit our website at 800-423-6967; www.gallipot.com
www.ijpc.com.
133 Health Engineering Systems
All rights reserved. Permission is granted for libraries and others registered with the 888-Unguator; www.hescorp.net
Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923 USA, to
photocopy articles for a base fee of $25 per copy of the article plus $2 per page. Requests 125 KeyCentrix
for bulk orders should be addressed to the editor. 800-444-8486; www.flextraxsolutions.com

Indices 93 Letco
IJPC is indexed by: 800-239-5288; www.letcomedical.com
• International Pharmaceutical Abstracts
• Cumulative Index to Nursing & Allied Health Literature Print Index and Database IBC MEDISCA
800-932-1039; www.medisca.com
• Chemical Abstracts
• Elsevier Bibliographic Databases, including: 103 Paddock
EMBASE Mosby Yearbooks 800-328-5113; www.paddocklabs.com
EMNursing Scopus
Compendex Other specialized niche databases and derivative products 116, 117 PCCA
GEOBASE 800-331-2498; www.pccarx.com

149 QI Medical
Erratum 800-837-8361; www.qimedical.com
Allen LV Jr. Nicotine rectal enema. IJPC 2009; 13(2): 158. The formula for nicotine rec-
99 Robert P. Potts & Associates
tal enema requires 6 mg of nicotine base. This is equal to 18.4 mg of nicotine tartrate. 800-255-5498; www.robtpotts.com

141 Spectrum Pharmacy Products

F o r a dv e rt i s i n g i n fo r m at io n , 800-791-3210; www.spectrumrx.com
co n tac t L au r e n B e r n ic k IFC ZRT
T: 800-757-4572 / 405-330-0094 ext. 4 F: 877-781-5107 E: lbernick@ijpc.com 888-572-5482; www.zrtlab.com

Copyright 2010 by the International Journal of Pharmaceutical Compounding.™

International Journal of Pharmaceutical Compounding www.ijpc.com

176 Vol. 14 No. 3 | May/June 2010
 MEDISCA NETWORK
COMPOUNDING TRAINING 2010
CHOOSE YOUR COURSE...

Training Program DaTe LocaTion Learn How To...

February 19 – 21 (Sold Out) • Design & prepare dosage forms

non-STeriLe May 14 – 16, 2010 • Market & promote your practice
Gainesville, Florida • Raise your standard of practice
comPounDing August 27 – 29, 2010
• Comply with regulatory guidelines
November 5 – 7, 2010
• Prevent calculation errors
• Implement a Quality First® initiative
non-STeriLe Coming Soon Richmond, • Assess clinical cases & develop treatment plans
comPounDing September 2010* British Columbia • Use a full complement of compounding technology
• Package & label your finished preparations

• Perform aseptic techniques

• Perform workflow assessments
STeriLe March 19 – 21, 2010
Gainesville, Florida • Enter & exit a clean room environment
comPounDing October 22 – 24, 2010
• Prepare compounded sterile preparations
• Control, perform, validate & document work tasks
• Minimize clinical, regulatory & legal risk
• Conduct clean room maintenance procedures
STeriLe Coming Soon Richmond, • Monitor & sustain a sterile environment
comPounDing November 2010* British Columbia • Adhere to USP 797 compliance standards
• Implement a Quality First® initiative

• Employ sterile environment principles & practices

aSePTic TecHniqueS March 18, 2010 • Perform aseptic techniques
Gainesville, Florida
Training October 21, 2010* • Manipulate technology in a sterile environment
• Garb & perform various workflow procedures

April 17 – 18, 2010 Las Vegas, Nevada

Pain managemenT July 10 – 11, 2010
Seminar September 25 – 26, 2010
December 11 – 12, 2010
• Develop collaborative clinical practice models
Orlando, Florida
• Target pathophysiological pathways
Las Vegas, Nevada
• Apply drug mechanisms of action to clinical targets
Orlando, Florida

• Develop & implement business models

April 10 – 11, 2010
BuSineSS, markeTing June 5 – 6, 2010
anD SaLeS Seminar October 2 – 3, 2010
December 4 – 5, 2010
Orlando, Florida • Assess potential risks & capitalize on reward
Las Vegas, Nevada • Read financial statements & balance sheets
Orlando, Florida • Implement operational & logistical plans
Las Vegas, Nevada • Conduct comprehensive marketing & sales
• Establish collaborative clinical practice models

• Develop collaborative clinical practice models

• Compound for:
Hormone reSToraTion September 11 – 12, 2010* Orlando, Florida
- Hormone restoration; emphasis on sex steroids
Seminar October 16 – 17, 2010* Las Vegas, Nevada
- Adrenal / thyroid disorders & metabolic syndrome
• Employ a novel assessment protocol
Gainesville, Florida • Prepare non-sterile dosage forms
non-STeriLe Coming Soon and • Use a full complement of compounding technology
SkiLLS LaB Training 2-DAy prOgrAM Richmond, • Prevent calculation errors
British Columbia • Package & label finished preparations

To be added to a future correspondence list, send an e-mail to: information@medisca.net

*Tentative dates
If you have a specific program interest, please call our account executives at 1.866.333.7811

To Learn more caLL or ViSiT

1.866.333.7811
This program is supported by an unrestricted educational www.medisca.net
grant from the Medisca Group of Companies.
Administrative support provided by Medisca Network.
 ula for com d are ethox
ven form pou iers use yla
f
-pro nd
ing ulsi te-
fre
e m e
im E
T

TRADITIONAL FORMULA ETHOXYLATE-FREE

VaniBase
TM

Now you have two new options for an elegant, non-greasy, moisturizing cream.

VaniBase Traditional Formula is a standard oil-in-water emulsion vanishing cream.

VaniBase Ethoxylate-free is also an oil-in-water emulsion with "eco-certified" PEG-free

emulsifiers. This new formulation addresses concerns regarding products with 1,4
dioxane contamination.

Both formulas are Free of Dyes, Fragrance, Masking Fragrance, Lanolin, Parabens and
Formaldehyde.

Available in 1 lb, 5 lb and 25 lb sizes.

GALLIPOT®
The Art Of Compounding®

Call us at 1.800.423.6967 or visit us on-line at www.gallipot.com