EXTEMPORANEOUS

COMPOUNDING
 LEARNING OBJECTIVES
• Define the term extemporaneous compounding, and describe
common situations in which compounding is required.
• Identify and describe the equipment used for the weighing,
measuring, and compounding of pharmaceuticals.
• Use the proper technique for weighing pharmaceutical
ingredients.
• Use the proper technique for measuring liquid volumes.
 LEARNING OBJECTIVES
• Define the term percentage of error.
• Explain the process by which solutions, suspensions,
ointments, creams, powders, suppositories, and capsules
are prepared.
PRESCRIPTION SAMPLE
 COMPOUNDING

Is the preparation, mixing, assembling, altering, packaging, and

labeling of a drug, drug-delivery device, or device in
accordance with a licensed practitioner’s prescription,
medication order, or initiative based on the
practitioner/patient/pharmacist/compounder relationship in the
course of professional practice.

(USP 795)
 COMPOUNDING INCLUDES
THE FOLLOWING:
• Preparation of drug dosage forms for both human and animal
patients
• Preparation of drugs or devices in anticipation of prescription
drug orders based on routine, regularly observed prescribing
patterns
• Reconstitution or manipulation of commercial products that
may require the addition of one or more ingredients
• Preparation of drugs or devices for the purposes of, or as an
incident to, research (clinical or academic), teaching, or
chemical analysis
• Preparation of drugs and devices for prescriber’s office use
where permitted by federal and state law
 EXTEMPORANEOUS COMPOUNDING

• Is the preparation of a therapeutic product for

an individual patient in response to an
identified needed
• Is defined as they timely preparation of good
drug product according to another physician's
prescription, in which the amounts of
ingredients are calculated to meet the needs of
a particular patient or a group of patients
according to “Good Manufacturing Practice”
 COMPOUNDING
Extemporaneous compounding
 On-demand preparation of a drug product.

 According to a physician’s prescription.

 Meets the unique needs of an individual

patient.
Manufacturing
 The production or processing of a drug in a

LARGE quantity by various mechanisms.

 WHY COMPOUND?
1. Pediatric patients requiring diluted adult strengths of drugs.
2. Patients needing an oral solution or suspension of a product
that is only available in another form.
3. Patients with sensitivity to dyes, preservatives, or flavoring
agents found in commercial formulations.
4. Dermatological formulations with fortified (strengthened) or
diluted concentrations of commercially available products.
5. Specialized dosages for therapeutic drug monitoring.
6. Care for hospice patients in pain management.
Compounding for animals.
 Compounding Issues

Disclaimer:
• Products compounded for veterinary use cannot
be used in humans.
 COMMON PROBLEM WITH SPECIAL
PRESCRIPTIONS
1. If short dated-will patient use up quantity prescribed within that
time
2. Cost if using special company-very important if private
prescription
3. Lack of detail on prescription especially creams and ointments
where no base is indicated
4. Computer generated prescriptions where inlicensed
preparations are not in the standard menus.
5. Finding a formula.
6. National differences with non-compedial formula.
 PRESCRIPTION ANALYSIS:
COMPOUNDING CONSIDERATIONS
 Always consider the use of commercially available products as far
as possible.
 If no suitable commercial product exists, consider a therapeutic
alternative that is available in a suitable dosage form. This must
be discussed with the physician.
 Extemporaneous preparations should be done based on
evidence-based references.
 Always check for the suitability of the product/brand for
extemporaneous preparations.
 Preparations should be done according to what is stated as far as
possible unless stated otherwisein the product leaflet.
 PRESCRIPTION ANALYSIS:
COMPOUNDING CONSIDERATIONS
 When no information is available, compound an oral medication
by dispensing a tablet and/or capsule and directing the caregiver
to mix just prior to administration.
 Stability for shelf storage in the pharmacy is applicable without
opening. Once opened, the stability of the preparation should be
no longer than 30 days. Maximum quantity of the
extemporaneous preparations to be dispensed should mot exceed
one month.
 Refrain assumptions on the therapeutic equivalence in the case of
suggesting alternative agents as the possibilities and supporting
data may be limited
 PRESCRIPTION ANALYSIS:
COMPOUNDING CONSIDERATIONS
 Techniques in compounding preparations and manipulations
should always be in line with the standard Good Preparation
Practice as delivering an accurate dose is paramount.
 Staff and facilities are challenged to undertake intermittent
competency assessments in order to achieve the standards
requirement.
 Documentation after each preparation should include details on
the materials used, processes involved and the responsible
personnel in-charge.
 CONSIDERATIONS FOR PREPARING
EXTEMPORANEOUS COMPOUNDS
 Pharmacy personnel are reminded not to empirically change flavourings or
suspending agents because they can affect the pH and stability of the product
and result in an unstable product.
 Please consider ingredients in the formulations that require special
precautions in neonates.
 Mixing of a compounded formulation should always be in line with the
following principles:
a) Ensure that all ingredients used are within the expiry date.
b) Ensure that all utensils are clean; including mortar and pestle, graduates, pill cutters
and stirring rods.
c) Product should be labelled clearly and stored as recommended within the formula.
d) For solution or suspension products, emphasise on the importance of thorough
shaking before administration.
 CONSIDERATIONS FOR PREPARING
EXTEMPORANEOUS COMPOUNDS
 If compounding a preparation using contents from an ampoule, remember to
withdraw the solution (medication) from the ampoule using a filter needle to
ensure no glass particles are incorporated into the compound.
 Place tablet(s) within mortar and pestle to grind tablets to a fine powder. For
film-coated tablets, it may be necessary to add a small amount of diluents such
as water, to soften the coating prior to grinding the tablets. This will ensure
that the compound will not have an eggshell appearance from the film coating
floating throughout the suspension. If you are using capsules, open the
capsule and empty the powder into the mortar and discard the capsule shell.
 Solutions will have a clearer appearance versus a compounded suspension.
 CONSIDERATIONS FOR PREPARING
EXTEMPORANEOUS COMPOUNDS
 Manipulations of the available dosage forms in order to fulfil the
unusual practitioner’s request may impose risks such as
preparation and administration errors as well as unpredictable
bioavailability, compatibility and stability profile.
 Understand the roles of excipients in certain formulations and
consider their risks over benefits limitation.
 If distilled water is not available, water for injection can be used
as a substitution, and vice versa.
 SOURCES OF FORMULAE
 Compendia e.g. BP, Martindale 28th/USP/NF etc
 Hospital-often continuation of treatment in primary care.
 GP’s own e.g Dr Ives wart paint etc
 Published literature/journal articles available on internet. Often
American/European
Chapters <795>- called Pharmaceutical Compounding
- Nonsterile Preparations
 Published in 2000
 Enforceable

Chapter <797> - called Pharmaceutical Compounding - Sterile Preparations,

 Became official in 2004.

Other Chapters
 Containers <661>
 Good Compounding Practices <1075>
 Pharmaceutical Stability <1150>
 Pharmaceutical Dosage Forms <1151>
 EQUIPMENT FOR WEIGHING, MEASURING, AND
COMPOUNDING
• Balances: Balance measurements using a
counterbalance are made using sets of standardized
pharmaceutical weights. An electronic balance is easier to
learn and use and is more accurate than other types of
balances.
• Forceps and Spatulas: Forceps should be used when
picking up weights so that moisture and oils are not
transferred to the weights. Spatulas are used in
compounding tasks such as preparing ointments and
creams or loosening material from the surfaces of a
mortar and pestle.
 EQUIPMENT FOR WEIGHING, MEASURING, AND
COMPOUNDING
• Compounding Slab: This is an ideal surface for mixing
compounds because of its nonabsorbent surface.
• Mortar and Pestle: The coarser the surface of the
mortar and pestle, the finer the triturating, or grinding,
that can be done.
• Graduates and Pipettes: Graduates come in two
varieties: conical and cylindrical. A pipette is used for
measuring liquids with a volume less than 1.5 mL
 EQUIPMENT FOR WEIGHING, MEASURING, AND
COMPOUNDING

• Master Formula Sheet: Prepared by the

pharmacist, this sheet indicates the amount of
each ingredient needed, lists the procedures to
follow, and provides the labeling instructions.
 TECHNIQUE FOR WEIGHING PHARMACEUTICAL
INGREDIENTS

• Weighing of the product is one of the most

essential parts of the compounding process.
• Weighing the exact amount prescribed is
essential in compounds for several reasons: the
product cannot be “checked” for content once
mixed, the quantities weighed out are often very
small, and a slight overage could mean a serious
overdose for the patient.
Weighing Pharmaceutical
Ingredients
1. Unlock the balance and confirm that it is
leveled, front to back and side to side, using the
leveling screws at its base. Once this is done, the
balance is ready to use. Lock the balance once
again, before transferring weight to it.
Weighing Pharmaceutical
Ingredients
2. Place weighing papers on the two pans of the
balance. These papers should be of exactly the
same size and weight. The edges of the paper on
the left-hand pan may be folded upward, to hold
the substance to be weighed. Do not place any
materials on the weighing pans without using
weighing papers.
Weighing Pharmaceutical
Ingredients

3. Unlock the balance to confirm that the

balance is still leveled, and then lock it again.
Weighing Pharmaceutical
Ingredients
4. Add the forceps to transfer the weight from
the weight container. desired weight to the right-
hand pan, using
Weighing Pharmaceutical
Ingredients
5. Place an approximate amount of the material
to be weighed onto the left-hand pan, using a
spatula to transfer it.
Weighing Pharmaceutical
Ingredients
6. Slowly release the beam using the unlocking
device at the front of the balance, and check the
balance.
Weighing Pharmaceutical
Ingredients
7. If the amount of the substance being weighed
is too great or too small, lock the balance again
and use a spatula to add or remove material.
Weighing Pharmaceutical
Ingredients

8. Slowly release the beam using the unlocking

device and check for equilibrium.
Weighing Pharmaceutical
Ingredients
9. Once a nearly precise amount of material has
been transferred to the pan, a very small
adjustment upward can be made by placing a
small amount of material on the spatula, holding
the spatula over the left pan, and lightly tapping
the spatula with the forefinger to knock a bit of
the substance onto the pan. This is done with
the balance unlocked and the balance beam free
to move.
Weighing Pharmaceutical
Ingredients
10. Lock the balance, close the lid, and then
unlock the balance to make a final
measurement.
Weighing Pharmaceutical
Ingredients
11. Lock the balance before removing the
measured substance. Use transfer forceps to
remove the weights and return them to their
storage case.
TECHNIQUE FOR MEASURING LIQUID VOLUMES

A general rule of thumb is to always select the

device that will give you the most accurate
volume. Selecting a container that will be at least
half full when measuring, or using the smallest
device that will hold the required volume, is
considered good practice.
Measuring Liquid Volumes
1. Choose a graduate with a capacity that equals or very
slightly exceeds the total volume of the liquid to be
measured. Doing so reduces the percentage of error in the
measurement. In no case should the volume to be
measured be less than 20% of the total capacity of the
graduate. For example, 10 mL of liquid should not be
measured in a graduate exceeding 50 mL in capacity.
Again, the closer the total capacity of the graduate to the
volume to be measured, the more accurate the
measurement will be.
Measuring Liquid Volumes

2. Bear in mind that the more narrow the column

of liquid in the graduate, the less substantial any
reading error will be. Thus for very small volume
measurements a cylindrical graduate is
preferable to a conical graduate.
Measuring Liquid Volumes

3. Pour the liquid to be measured slowly into the

graduate, watching the level of the liquid in the
graduate as you do so. If the liquid is viscous, or
thick, then you should attempt to pour it toward
the center of the graduate to avoid having some
of the liquid cling to the sides.
Measuring Liquid Volumes

4. Wait for liquid clinging to the sides of the

graduate to settle before taking a measurement.
Measuring Liquid Volumes

5. Measure the level of the liquid at eye level and

read the liquid at the bottom of the meniscus
(see Figure 8.3).
Measuring Liquid Volumes

6. When pouring the liquid out of the graduate,

allow ample time for all of the liquid to drain.
Bear in mind that depending on the viscosity of
the liquid, more or less will cling to the sides of
the graduate. For a particularly viscous liquid,
some compensation or adjustment for this
clinging may have to be made.
 PERCENTAGE OF ERROR

Error in measurement in pharmacy-

prepared products is expected, and
allowances are made for a certain
percentage of error over or under the target
measurement. This percent of error is
considered to be a range both above and
below the target measurement, and being
over or under (i.e., positive or negative)
within this range is not consequential.
 COMMINUTION AND BLENDING OF DRUGS

• Geometric Dilution Method: A way to combine drugs

using a mortar and pestle.
• Examples of Compounding Preparations: The
following are some common examples of compounding in
the community pharmacy: solutions, suspensions,
ointments and creams, powders, suppositories, and
capsules.
 COMMINUTION AND BLENDING OF DRUGS

• Labeling, Record Keeping, and Cleanup: After

compounding, the product must be labeled with a
prescription label, and a careful record of the
compounding operation should be kept. Once the
compounding operation is finished, the equipment
and area should be cleaned and everything should
be returned to their proper places in storage.
 COMPOUNDING OF SOLUTION
Definition:
A solution as a liquid preparation that contains one or
more chemical substances dissolved in a suitable solvent or
mixture of mutually miscible solvents. Although the
uniformity of the dosage in a solution can be assumed, the
stability, pH, solubility of the drug or chemicals, taste (for oral
solutions) and packaging need to be considered.

Types of solutions
1. Sterile parenteral and ophthalmic solutions:
These solutions require special consideration for their
preparations.
2. Nonsterile solutions: Include oral, topical and otic solutions
 COMPOUNDING OF SOLUTIONS
Preparations of Solutions:
1. Each drug chemical is dissolved in the solvent in which it is most soluble.
Thus, the solubility characteristics of each drug or chemical must be
known.
2. If an alcoholic solution is used, the aqueous solution is added to
the alcoholic solution.
3. The salt form of the drug and not the free-acid or base form, which
both have poor solubility, is used.
4. Flavoring or sweetening agents are prepared ahead of time.
5. If the required chemical or drug is in bulk or powder from, then the
particle size is reduced first, using a mortar and pestle, a sieve or other
suitable means.
6. The proper vehicle (e.g. syrup, elixir aromatic water, purified water) must
be selected.
COMPOUNDING OF SUSPENSION

• Definition: Suspensions are defined by the USP as liquid

preparations that consist of solid particles dispersed
throughout a liquid phase in which the particles are not
soluble.
• Preparation of suspensions
1. The insoluble powders are triturated to a fine powder,
using a Wedgwood mortar.
2. A small portion of liquid is used as levigating agent and
the powders are triturated until a smooth paste is
formed. The levigating agent is added slowly and mixed
COMPOUNDING OF SUSPENSION
3. The vehicle containing the suspending agent is added in
divided portions. A high-speed mixer greatly increases the
dispersion.
4. The product is brought to the required volume using the
vehicle.
5. The final mixture is transferred to a “tight” bottle for
dispensing to the patient.
6. All suspension are dispensed with a “shake well” label.
7. Suspensions are never filtered.
8. The water-soluble ingredients are mixed, including flavoring
agents, in the vehicle before mixing with the insoluble
ingredients.
 EMULSIONS
• Definition: Emulsions are produced by a two-phase
system in which one liquid is dispersed throughout
another liquid in the form of small droplets.

• Preparation of emulsion:
1. A mortar and pestle are frequently all the equipment
that is needed.
2. Electric mixers and hand homogenizers are useful for
producing emulsions after the coarse emulsion is
formed in the mortar
 EMULSIONS
3. The order of mixing of ingredients in an emulsion depends on the type of
emulsion being prepared (i.e., O/W or W/O) as well as the emulsifying
agent chosen. Methods used for compounding include the following.
a. Dry gum (continental) method
b. Wet gum (English) method
c. Bottle method
d. Beaker method

4. Preservatives: If the emulsion is kept for an extended period of time,

refrigeration is usually sufficient. The product should not be frozen. If a
preservative is used, it must be soluble in the water phase to have any
effect.
5. Flavoring agents: If the addition of a flavor is needed to mask the taste of
the oil phase, the flavor should be added to the oil before emulsification.
POWDERED DOSAGE FORMS
Definition: Powders are dry mixtures of drugs or chemicals intended
for internal or external use. The two major types are powder papers
and bulk powders.
• Preparation of powder dosage forms
1. Bulk powders, which may be used internally or topically, include
dusting powders, douche powders, laxatives, antacids and
insufflations powders.
2. After a bulk powder has been pulverized and blended, it should be
dispensed in an appropriate container
3. Eutectic mixtures of powders can cause problems since they liquify.
One remedy is to add an inert powder, such as magnesium oxide, to
separate the eutectic materials.
4. Powder papers are also called divided powders.
CAPSULES
Definition: Capsules are solid dosage forms in which the drugs is enclosed
within a hard or soft soluble container or shell made form suitable
gelatin. Hard gelatin capsules may be manually filled for extemporaneous
compounding.

Preparation of hard and soft capsules

1. As with the bulk powders, all ingredients are triturated and blended,
using geometric dilution.
2. The correct size capsules must be determined by trying different
capsule sizes, weighing them and choosing the appropriate size.
3. Prior to filling capsules with the medication, the body and cap of the
capsule are separated. Filling is accomplished by using the “punch”
method.
4. The capsule is wiped clean of any powder or oil and dispensed in a
suitable prescription vial.
 MOLDED TABLETS (TABLET TRITURATES)
Definition: Tablet triturates are molded tablets made of powders created by
moistening the powder mixture with alcohol and water. They are used for
compounding potent drugs in small doses.
Formulation and preparation of tablet triturates
1. Tablet triturates are made in special molds consisting of a pegboard and a
corresponding perforated plate.
2. In addition to the mold, a diluent, usually of lactose and sucrose (80/20),
and a moistening agent, usually a mixture of ethyl alcohol and water
(60/40) are required.
3. The diluent is triturated with the active ingredients.
4. A paste in then made, using the alcohol and water mixture.
5. This paste is spread into the mold, allowed to dry and then punched
OINTMENTS, CREAMS, PASTE
AND GELS
General characteristics: These dosage forms are semisolid
preparations generally applied externally.
Semisolid dosage forms may contain active drugs intended to:
1. Act solely on the surface of the skin to produce
a local effect (e.g. antifungal agent)
2. Release the medication, which, in turn,
penetrates into the skin (e.g., cortisol cream)
3. Release medication for systemic absorption
through the skin (e.g., nitroglycerin)
 OINTMENTS, CREAMS,
PATES AND GELS
• Preparation of ointments, creams, pastes and gels
1. Mixing can be done in a mortar or on an ointment slab
2. Liquids are incorporated by gradually adding them
to an absorption-type base, using levigation
3. Insoluble powders are reduced to a fine powder
and then added to the base, using geometric dilution
4. Water-soluble substances are dissolved with water
and then incorporated into the base.
5. The final product should be smooth (impalpable)
and free of any abrasive particles.
 SUPPOSITORIES
• General characteristics:
1. Suppositories are molded solid dosage forms
intended for insertion into a body cavity. They are
used to deliver drugs for their local or systemic
effects.
2. Suppositories differ in size and shape and include:
a. Rectal
b. Vaginal
c. Urethral
d. Nasal
 SUPPOSITORIES
• Methods of preparation and dispensing suppositories
1. Molded suppositories: are prepared by first melting the base and then
incorporating the medications uniformly into the base. This mixture is then
poured into the suppository mold (fusion method).
2. Hand-rolled suppositories: required a special technique. With proper
technique, it is possible to make a product equal to the molded
suppositories.
3. Containers: for the suppositories are determined by the method and base
in preparation. Hand-rolled and molded suppositories should be
dispensed in special boxes that prevent the suppositories from coming in
contact with each other.
4. Storage conditions: If appropriate, a “refrigerate” label appear on the
container. Regardless of the base or medication used in the formulation,
the patient should be instructed to store the suppositories in a cool dry
place.
PARENTERAL PRODUCTS
• General requirements. The extemporaneous compounding of sterile
products is no longer confined only to the hospital environment; it now is
done by community pharmacists engaged in home care practice. Minimum
requirements include:
1. Proper equipment and supplies.
2. Proper facilities, including a laminar flow clean bench.
3. Proper documentation of all products made.
4. Quality control, including batch sterility testing.
5. Proper storage both at the facility and while the product is in transport
to the patients home.
6. Proper labeling of the prescription product.
7. Knowledge of products stability and incompatibilities.
8. Knowledge of all ancillary equipment involved in production or delivery of
the medications.
PARENTERAL PRODUCTS
Preparation of parenteral products
1. Preparation of sterile products requires special skills and training.
Attempts to prepare parenteral products or provide this service
without proper training should not be made.
2. These products must be prepared in a clean room, using aseptic
technique (i.e., working under controlled conditions to minimize
contamination).
3. Dry powders of parenteral drugs for reconstitution are used for drug
products that are unstable as solutions. It is important to know the
correct diluents that can be used to yield a solution.
4. Solutions of drugs for parenteral administration may also be further
diluted prior to administration. If further dilution is required, then the
pharmacist must know the stability and compatibility of the drug in the
diluent.
 Discussion
The art of compounding uses a whole different language,
and you have been asked to describe the following terms to
a pharmacy student who is visiting your pharmacy. Use
simple terms.

a. levigate f. tumbling
b. punch method g. solute
c. triturate h. solvent
d. spatulation i. geometric dilution
e. diluent j. comminution