Suppositories and Inserts

Chapter 12

Suppositories
-Are solid dosage forms intended for insertion
into body orifices where they melt, soften, or
dissolve and exert local or systemic effects.
-Derived from Latin word supponere, meaning
to place under.
-Are commonly used rectally and vaginally
and occasionally urethrally.

COMPARISON BETWEEN DIFFERENT TYPES OF

SUPPOSITORIES
Suppositories

Physical
Appearance

Size/ Weights

Shape

RECTAL
=Adult

32 mm (1.5)
long; 2g (w/
base)

Bullet-like
Torpedo or
Little finger

=Infants/Childre
n

Half the size &

weight of adult
supp..

Pencillike

Vaginal(Pessarie
s)

5g(when cocoa
butter is the
base)

Globular
Oviform or
Cone-shaped

Suppositories

Physical
Appearance

Size/ Weights

Shape

Urethral(Bougie
s)
=Male

3-66 mm in
diameter; 140
mm long
4g weight

Slender
Pencil-shaped

=Female

Half the length

& weight of
male;
70 mm long; 2g

Local action
Rectal suppositories intended for local
action are most frequently used to relieve
constipation or the pain, irritation, itching,
and inflammation associated with
hemorrhoids or other anorectal
conditions.
A popular laxative, glycerin suppositories
promote laxation by the local irritation of
the mucous membranes.

Vaginal suppositories intended for local

effects are employed mainly as
contraceptives, antiseptics in feminine
hygiene, and as specific agents to combat
an invading pathogen.
Nonoxynol-9 for contraception, and
trichomonacides to combat vaginitis
caused by Trichomonas vaginalis, Candida
(Monilia) albicans, and other
microorganisms.

Systemic action
For systemic effects, the mucous
membranes of the rectum and vagina
permit the absorption of many soluble
drugs.
Although the rectum is used frequently
as the site for the systemic absorption
of drugs, the vagina is not as frequently
used for this purpose.

Advantages over oral therapy of

the rectal route of
administration:

a) Drugs destroyed or inactivated by the pH or enzymatic

activity of the stomach or intestines need not be
exposed to these destructive environments;
b) Drugs irritating to the stomach may be given without
causing such irritation
c) Drugs destroyed by portal circulation may bypass the
liver after rectal absorption
d) The route is convenient for administration of drugs to
adult or pediatric patients who may be unable or
unwilling to swallow medication
e) It is an effective route in the treatment of patients with
vomiting.

Examples of drugs administered

rectally
Prochlorperazine and chlorpromazine- for the relief of
nausea and vomiting and as tranquilizer
Oxymorphone HCl- for opioid analgesia
Ergotamine tartrate- for the relief of migraine syndrome
Indomethacin- nonsteroidal anti-inflammatory analgesic
and antipyretic
Ondansetron- for the relief of nausea and vomiting

Some factors of drug absorption from

rectal suppositories

Divided into two main groups:

1)Physiologic Factors
Colonic content
Circulation route
pH and Lack of Buffering Capacity of the Rectal Fluids

2) Physicochemical Factos
Lipid-water solubility
Particle size
Nature of the base

Physiologic Factors
Colonic content
-It is more effective for a drug to absorbed
systematically in an empty rectum than from one that
is distended with fecal.
Circulation route

-Drugs absorbed in the rectum bypass the first pass

effect in the liver instead of being absorbed into
general circulation.
-Lymphatic circulation also assists in the absorption of
rectally administered drugs.

Physiologic Factors
pH and Lack of Buffering Capacity of the
Rectal Fluids
-Rectal fluids are essentially neutral in pH and
have no effective buffer capacity, the form in
which the drug is administered will not generally
be chemically changed by the rectal
environment.
-The suppository base employed has a marked
influence on the release of active constituents
incorporated into it.

Physicochemical factors of the drug

and suppository base

Lipid-water solubility
-A lipophilic drug that is distributed in a fatty
suppository base in low concentration has
less of a tendency to be released into the
body fluid, than in a fatty base.

 Particle size
-For drugs present in a suppository in the
undissolved state, the size of the drug
particle will influence its rate of dissolution
and its availability for absorption.
-The smaller the particle size, the more
readily the dissolution of the particle and
the greater the chance for rapid
absorption.

Nature of the base

-Base must be capable of melting, softening
or dissolving to release its drug absorption.
-If the base interacts with the drug to inhibit
its release, drug reaction will be impaired or
prevented.

Suppository bases
Should remain solid at room temperature but
soften, melt & dissolve readily at body
temperature.

Classification of suppository
bases
1) Fatty or oleaginous base

Cocoa butter- commonly used because it melts quickly at body

temperature.
Palm kernel oil & Cotton seed oil- have many hydrogenated fatty
acids of vegetable oil
Others:
Plamitic & Stearic acids-is one of the most common saturated
fatty acids found in nature followingpalmitic acid.
Wecobee Bases- triglycerides derived from coconut oil
Witepsol Bases- triglycerides from palm, palm kernel, and
coconut oils with self emulsifying glyceryl monostearate and
polyoxyl stearate.

2) Water-soluble and water-miscible

bases
Glycerinated gelatin
-is most frequently used in the preparation of
vaginal suppositories, where the prolonged
localized action of the medicinal agent is
usually desired.
Polyethylene Glycol
-used to prepare progesterone vaginal
suppository for premenstrual syndrome.

3) Miscellaneous bases
-mixtures of oleaginous and water-soluble or
water-miscible materials,
-some are preformed emulsions, generally of
the water/oil type, or they may be capable of
dispensing in aqueous fluids.
E.g. Polyoxyl 40 stearate

Preparation of
suppositories
A. Molding from a melt
B. Compression
C. Hand rolling & shaping

A Preparation by molding
The steps in molding include
melting the base,
incorporating any required medicaments,
pouring the melt into molds,
allowing the melt to cool and congeal into
suppositories,
removing the formed suppositories from
the mold.

Suppository molds
Commercially available molds can produce
individual or large numbers of
suppositories of various shapes and sizes.
Molds in common use today are made from
stainless steel, aluminum, brass, or plastic.
Individual plastic molds may be obtained
to form a single suppository.

Lubrication of the mold

Depending on the formulation,
suppository molds may require
lubrication before the melt is poured to
facilitate clean and easy removal of the
molded suppositories.
Lubrication is seldom necessary when
the suppository base is cocoa butter or
polyethylene glycol.
Lubrication is usually necessary when
glycerinated gelatin suppositories are
prepared.

Calibration of the mold

Each individual mold is capable of holding a
specific volume of material in each of its
openings.
The pharmacist should calibrate each
suppository mold for the usual base so as to
prepare medicated suppositories each
having the proper quantity of medicaments.

Preparing and Pouring the

Melt

Using least heat, the weighed

suppository base materials is melted
over a water bath.
A porcelain casserole is best used
because it later permits convenient
pouring of melt into the cavities of
the mold.

B) Preparation by compression
-may be prepared by forcing the mixed
mass of the base and the medicaments
into special molds using suppositorymaking machines.
-In preparation of compression into the
molds, the base and the other formulative
ingredients are combined by thorough
mixing, the friction of the process
softening the base into a pastelike
consistency.

Compression is especially suited for

making suppositories that contain heatlabile medicinal substances or a great
deal of substances that are insoluble in
the base.
The disadvantage to compression is that
the special suppository machine is
required and there is some limitation as
to shapes of suppositories that can be
made.

Preparation by Hand rolling and

Shaping
The oldest and simplest method
of suppository preparation.
Method of choice when only a few
suppositories are to be prepared
in a cocoa butter base.

Rectal Suppositories
The rectal route of administration is especially
useful in instances in which the patient is
unwilling or unable to take medication by mouth.
They are also intended to provide local action
within the perianal area.
They are commonly employed to relieve:
-Pruritis ani
-Pain sometimes associated with hemorrhoids

Examples of Rectal Suppositories

Suppositories

Commercial Product

Active
Constituent
s

Type of
Effect

Category and
Comments

Bisacodyl

Dulcolax (BoehringerIngelheim)

10 mg

Local

Cathartic

Chlorpromazine

Thorazine(GlaxoSmith
Kline)

100 mg

Systemic

Antiemetic;
tranquilizer

Hydrocortisone

Anusol-HC (Salix)

25 mg

Local

Pertusis ani,
inflamed
hemorrhoids,
other
inflammatory
conditions of the
anorectum.

Hydromorphone

Dilaudid (Abbott)

3 mg

Systemic

Analgesic

Indomethacin

Indocin

50 mg

Systemic

Antiinflammatory

Mesalamine

Canasa (Axcan
Scandipharm)

500 mg

Local

Antiinflammatory

Oxymorphone
Prochlorperazine

Numorphan (Endo)
Compazine (SmithKline
Beecham)
Phenergan (Wyeth)

5 mg
2.5, 5, 25 mg

Systemic
Systemic

Analgesic
Antiemetic

12.5, 25 mg

Systemic

Antihistamine,
antiemetic,
sedative

Promethazine HCL

Urethral Suppositories
Are also called Bougies. They have
been used in the treatment of local
infections, and a much smaller
urethral suppository been
introduced for the administration of
alprostadil in the treatment of
erectile dysfunction.

Vaginal Suppositories
These preparations are employed
principally to combat infections in
the female genitourinary tract to
restore the vaginal mucosa to its
normal state and for
contraception.

Examples of Vaginal Suppositories

Product
(Manufacturer)

Active Constituents

Cleocin supp(Pfizer)

Clindamycin phosphate 100 mg

Bacterial vaginosis

Monistat 7 supp
(Personal Products)

Miconazole nitrate 100 mg

Antifungal for local

vuvlvovaginal
Candidiasis
(moniliasis)

Mycelex-G vaginal
contraceptives
(Bayer)

Clotrimazole 500 mg

Vulvovaginal yeast
(Candida) infections

Semicid vaginal
contraceptive inserts
(Whitehall-Robins)

Nonoxynol-9 100 mg

Nonsystemic
reversible birth
control

Encare contraceptive Nonoxynol-9 100 mg

inserts (Blaire)

Nonsystemic
reversible birth
control

Nanoxynol-9, a spermicide, is
employed for vaginal
contraception
Estrogenic substances as
dienestrol are found in
vaginal prepareations to
restore the vaginal mucosa to
its normal state.

Vaginal Inserts
Vaginal tablets, frequently referred to
as vaginal inserts, are usually ovoid in
shape and are accompanied in their
packaging with a plastic inserter.

They are prepared by tablet

compression, and are commonly
formulated to contain
lactose as the base or filler
starch as the disintegrating agent
polyvinylpyrrolidone as a dispersing
agent
magnesium stearate as a tablet lubricant.

Packaging and storage

Glycerin suppositories and glycerinated gelatin
suppositories
-are packaged in tightly closed glass containers to prevent a
moisture change in the content of the suppositories.
-stored at temperature below 35 F
-can be stored at controlled room temperature
(20 C to 25 C)

Suppositories prepared from a cocoa butter

base
-are usually individually wrapped or otherwise separated in
compartmentalized boxes to prevent contact and
adhesion.

Suppositories containing lightsensitive drugs

-are individually wrapped in an opaque
material such as metallic foil.
Suppositories are also commonly packaged in
slide boxes or in plastic boxes.

Glycerinated gelatin suppositories

are best stored at temperatures
below 8C and can routinely be
stored at controlled room
temperature (2025C).
Suppositories made from a base
of polyethylene glycol may be
stored at usual room
temperature.