Assist in Extemporaneous Preparation

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 Extemporaneous Preparation
1.1. Introduction
 Compounding: is the preparation, mixing,
assembling, packaging or labeling of a drug in
response to a prescription written by a licensed
practitioner.
 Extemporaneous Preparation: defined as the preparation,
mixing, assembling, packaging and labelling of a medicinal
product based on a prescription order from a licensed
practitioner for the individual patient.
 It is the timely preparation of a drug product according
to a physician‘s prescription, a drug formula, or a
recipe in which calculated amounts of ingredients are
made into a homogenous (uniform) mixture.
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 It is usually prepared due to lack of commercially available
formulations for patients with specific needs.
 Compounding of extemporaneous preparations consists of
two main components:
• Active ingredients, and
• Excipients
 Active ingredient: defined as any component that provides
pharmacological activity to affect the structure or any
function of the body of man or animals.
 Excipients: are the vehicles and diluents for the active
ingredient.
 There are many kinds of excipients that can be used as the
vehicle or suspending agent during extemporaneous
preparation. e.g. acacia, tragacanth, hydroxymethycellulose,
sugar, carboxymethylcellulose, sorbitol and glycerin.
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 Extemporaneous preparations are required by patients
who are unable to swallow the oral solid medications such
as neonates, pediatric patients and patients having throat
problems.
 Therefore, most of the extemporaneous preparations
involve the process of compounding of oral solid
medications into oral liquid forms such as solutions or
suspensions.
1.2. Distinguishing Extemporaneous Compounding from
Manufacturing
 Extemporaneous compounding:
 On-demand preparation of a drug product
 According to a physician’s prescription
 Meets the unique needs of an individual patient

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 Manufacturing:
 The production or processing of a drug in a LARGE
quantity by various mechanisms.
 Reasons for Extemporaneous Compounding:
 Unavailable dosages, strengths and routes of commercial
products
 Dilution of adult doses of medications to Pediatric patients
 Conversion of solid dosage forms to solutions or
suspensions
 Combination of topical dermatological products not
available by the manufacturer
 Inactive ingredients of commercial products which may
cause allergic reactions in individuals

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1.3.The compounding process
 During the compounding process, the compounder
adheres to strict procedures to ensure the safety of the
patient for whom the extemporaneous formulation is
intended.
 Standards for extemporaneous compounding
 The products produced in the pharmacy must be suitable
for use.
 Accurately prepared to ensure the products meet the
required standard for quality assurance.
A. Personal hygiene and protective equipment
 Personal hygiene is extremely important because
medications are being prepared for patients who is ill.

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 Clean white coat should be worn to protect the
compounder from the product and, conversely, the product
from contamination from the compounder.
 During the compounding process, safety glasses and
gloves should always be worn.
 It is the responsibility of the individual compounder to
assess the risk posed by any pharmaceutical ingredient
and to ensure that the correct safety equipment is in use.
 Similarly, long hair should be tied back and hands washed,
ensuring any open cuts are covered.
B. Clean work area and equipment
 Before starting to compound a product, the work area and
equipment should be cleaned with a suitable solution which
must be allowed to dry fully.
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 Properly clean and disinfect work areas and equipment to
prevent the spread of infection or contamination with
microorganisms.
C. Appropriate work area
 Consideration should be given to the work area to ensure
that it is suitable for its intended purpose.
 Both lighting and ventilation need to be adequate.
D. Label preparation
 The label for any pharmaceutical product must be prepared
before starting the compounding procedure.
 This reduces the possibility of the product being mislabeled
and given to the wrong patient.

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 Reasons for having labels:
 To give the patient clear and complete instructions on how
to use the preparations.
 To indicate the storage condition necessary to ensure full
potency through the period of treatment.
 To uniquely identify the contents of the container.
 To increase patients‘ compliance by giving clear and
concise information about the preparation.
 To provide information about some cautions /warnings
about the preparations.

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 Requirements for labels
 There are both legal and professional requirements, which
must be complained between labeling a dispensed
medicine.
 It is the pharmacist responsibility to ensure that these
requirements are satisfies and that all labeling is accurate.
 Requirements for labeling compounded medicines:
 All labels must be type written or computer generated.
 The details, which must appear on the label of a dispensed
medicine are:
• Name and address of the pharmacy
• Patient‘s name
• Name of the preparation
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• Quantity of the preparation
• Formula of the preparation (for unofficial preparations
only)
• Strength of the preparation
• Use of the preparation • Instructions for the patient
• Date of compounding
• Beyond used date (shelf life)
• Storage conditions
• Additional label
• Precautions
• Advise

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 Stability and Beyond-use Dating (BUD)
 Stability: is the extent to which a dosage form retains the
same properties and characteristics that it possessed at
the time of its manufacture.
 Expiration date: is the date until which the manufacturer
can guarantee the safety and potency of a drug-product’s
stability.
 Beyond-use date: is the date after which a compounded
preparation is not to be used and is determined from the
date the preparation is compounded.
 Compounded preparations are intended for administration
immediately or following short-term storage.
 Compounders should consult and apply drug-specific and
general stability documentation and literature when
available. 12
 When assigning a BUD, compounders should
consider:
 Nature of the drug and its degradation mechanism
 Dosage form and its components
 Potential for microbial proliferation in the preparation
 Container in which it is packaged
 Expected storage conditions
 Intended duration of therapy
 BUD For Non-aqueous Liquids and Solid Formulations
(USP Chapter <795>)
 Refrigerated aqueous solution or suspension has a
beyond-use dating of 14-30 days.

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 Solids, like tablets and capsules and non-aqueous
solutions have a beyond-use date of 6 months or less.
 All other formulations have a 30-day beyond-use date or
duration of therapy, whichever date is earlier.
E. Weighing and measuring procedure
 During weighing and measuring, follow guidelines
F. Premises standards
 Premises where an extemporaneous product is being
prepared needs to be of an appropriate standard.
 Floor should be covered but in such a manner as to be
easily cleaned, surfaces should be smooth.
 Sinks should be clean and have a supply of hot and cold
water.
 There should be a functioning, clean refrigerator.
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H. Avoidance of contamination
 To avoid contamination of any extemporaneously prepared
product, compounders should adhere to the following
guidelines:
• Ensure all equipment is clean and dry prior to use.
• Keep the dispensing area clear of unnecessary items.
• Do not leave lids off stock bottles: always replace
immediately after use.
• Do not return material to stock containers once removed.
• Do not leave weighed and measured items unlabeled on
the work surface.
• Do not allow raw materials or the final product to come in
contact with the hands (if necessary wear gloves).

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I. Suitable record keeping
 Suitable record keeping is a vital part of good
extemporaneous preparation.
 Poor record keeping can lead to dispensing errors.
 Completion of the record will be another safety check for
the patient and is an essential part of any standard
operating procedure for extemporaneous dispensing.
1.4.Compound record
 Name, strength, and dosage form of the compounded
preparation (CP)
 Master Formulation Record reference for the CP, when
used

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 Date and time of preparation
 Assigned internal identification number (e.g., prescription
or lot number)
 Signature or initials of individuals involved in each step
(e.g., technician or pharmacist)
 Name, vendor or manufacturer, lot number, and expiration
date of each ingredient and container-closure system
 Weight or measurement of each ingredient
 Documentation of the calculations, made to determine and
verify quantities and/or concentrations of components, if
appropriate
 Documentation of quality control procedures in accordance
with the SOP (e.g., filter integrity, pH, and visual inspection)

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 Any deviations from the Master Formulation Record, if
used, and any problems or errors experienced during the
compounding of the CP
 Total quantity compounded
 Assigned Beyond Use Date
 Master formulation record is recommended when prepared
in batch or high risk of compounding.
1.5.Master formulation record
 Name, strength, and dosage form of the CP
 Physical description of the final preparation
 Identities and amounts of all ingredients and appropriate
container-closure systems

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 Complete instructions for preparing the CP, including
equipment, supplies, and a description of the compounding
steps
 BUD and storage requirements
 Quality control procedures (e.g., pH, filter integrity, and
visual inspection)
 Sterilization method, if applicable (e.g., filter, steam, or dry
heat)
 Any other information needed to describe the operation and
ensure its repeatability (e.g., adjusting pH and tonicity and
temperature)
 Other records (e.g. fridge temperatures) should be routinely
recorded.
 Refrigerator temperature between 2°C and 8°C

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Compounding Process Recoding Form (Compounding sheet)
Name of the dispensary/health institution _______________Date __________
Batch number/control number_________________ Batch quantity____________

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J. Storing or transporting the compounded product
 After drugs have been compounded and repackaged, they
must be properly stored.
 Appropriate storage requires environmental, security, and
safety considerations.
 Certain medications require storage that includes freezing,
refrigeration, light-protection, or room-temperature
conditions.
 Certain toxic chemicals should be kept inside cabinets and
kept low to the ground; they should never be stored out in
the open.
 The proper storage of every substance in the pharmacy is
the responsibility of all pharmacy employees.

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K. Patient Counseling
 Compounded prescriptions offer an excellent opportunity
for patient counseling.
 The compounder has to explain the prescription for the
patient and describe steps that are required before its
administration.
 Steps to be followed before, during, and after compounding
can be grouped into five categories:
• Preparatory,
• Compounding,
• Final check,
• Sign-off, and
• Cleanup steps.
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 In general, the common procedures in compounding of
extemporaneous preparations are listed below
1. Preparatory
 Judging the suitability of the prescription in terms of its
safety and intended use and the dose for the patient.
 Performing the calculations to determine the quantities of
the ingredients needed.
 Selecting the proper equipment and making sure it is clean.
 Donning the proper attire and washing hands.
 Cleaning the compounding area and the equipment, if
necessary.
 Assembling all the necessary materials and ingredients to
compound and package the prescription.
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2. Compounding
 Compounding the prescription according to the formulary
record or the prescription, using techniques of the art and
science of pharmacy.
3. Final Check
 Checking, as indicated, the weight variation, adequacy of
mixing, clarity, odor, color, consistency, and pH.
 Entering the information in the compounding log.
 Labeling the prescription.
4. Sign-Off
 Signing and dating the prescription, affirming that all of the
indicated procedures were carried out to ensure uniformity,
identity, strength, quantity, and purity.
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5. Cleanup
 Cleaning and storing all equipment
 Cleaning the compounding area
 Equipments used in pharmaceutical compounding
 A wide variety of equipment is used in extemporaneous
dispensing, depending on the product type to be prepared.
1. Mortars and pestles
 Mortars and pestles are used to:
• Mix powders
• Reduce the particle size of powders
• Grind crystals into powder form and liquids
• Make emulsions.
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 Noted that the mortar is the bowl and the pestle is the
pounding/shearing/grinding.
 In pharmacy two main types of mortar and pestle are
used:
a. Glass
 The surfaces of a glass mortar and its pestle are very
smooth, making them less suitable for size reduction of
powders, although they are efficient when grinding crystals
into powder form.
 Glass mortars are particularly useful when dissolving small
amounts of medicament, or
 When substances that are absorbed by and stain porcelain
mortars such as potassium permanganate or dyes.

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b. Porcelain
 Generally much larger than glass and used for large scale
production.

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2. Tiles or Slab
 Equipments used to prepare ointments by means of
trituration or levigation.
3. Spatula
 Equipments used to pick solid or semi solid ingredients,
and also used for levigation of ointment bases with other
ingredients on tiles.

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4. Stirring rods
 Equipments used to agitate liquids to speed up the
process of dissolution of solids.
 These are made of glass and normally between 20 and
30mm in length.

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5. Suppository moulds
 Traditionally, suppository moulds come in a range of sizes:
1 g, 2 g, 4 g and 8 g.
 May be metal or plastic
 Suppositories and pessaries are made using the moulds

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6. Water baths
 It is a laboratory equipment made from a container filled
with heated water.
 It is used to melt or heat reagents as required.

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7. Weighing balances
 Balance is one of important equipment used to weigh the
required amount of pharmaceutical ingredients in
pharmaceutical extemporaneous preparation.
 Types of balance:
a. Triple beam balance/Manual balance

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b. Digital/Electrical balance

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8. Watch glasses
 Watch glass is used as a surface to evaporate a liquid, to
hold solids while being weighed, for heating a small
amount of substance and as a cover for a beaker.

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9. Measuring apparatus
 They are glass or plastic equipments used to measure
different volumes of liquid ingredients.
 Some of them are the following.
• Cylindrical graduates
• Beakers
• Conical graduates
• Graduated pipettes
• Bottles Burette
• Dropper

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 Cylindrical and conical graduates

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 Graduated pipette

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 Beakers and dropper

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 Roles of Pharmacy Technicians in Compounding:
 Securing of all prescribed medications or devices from
inventory
 Measuring finished dosage forms
 Collecting ingredients for preparations
 Determining amounts of ingredients to be compounded
 Compounding sterile preparations using appropriate
aseptic technique, equipment, and devices
 Compounding cytotoxic or other hazardous preparations
 Disposing of hazardous or non-hazardous waste materials
 Packaging of finished preparations
 Generating accurate and complete labels and affixing them
appropriately
 Storing all medications correctly prior to dispensing
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 Manufacturing
 Manufacturing: is the production, preparation,
propagation, conversion, and/or processing of a drug or
device, through extraction from substances of natural
origin or through means of chemical or biological
synthesis.
 Includes any packaging or repackaging of the
substance(s) or labeling or relabeling of its container and
the promotion and marketing of such drugs or devices.

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 2. Obtain and process raw materials
1.1.Pharmaceutical raw materials:
 Active ingredients
 Excipients /additive
 Pharmaceutical packaging
 Drug = API (Active Pharmaceutical Ingredient) + Non-
API (Excipient)
 Non-API: Material that is deliberately incorporated into the
formulation to aid some physicochemical process of drug
manufacturing.
 It has no pharmacological action but establish the primary
features of the product Physical form, texture, stability,
taste, appearance.

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 Commonly used pharmaceutical ingredients
A. Pharmaceutical solvents:
 Used to dissolve substances in preparation
 The most common solvent is water
B. Preservatives:
 Prevents the formulation from chemical, physical and
microbial degradation
E.g. Benzoic acid, boric acid, Sorbic acid, Benzalkonium
Chloride, Phenols, Alcohols, etc.
C. Anti-oxidant:
 Prevent the degradation of a drug by oxidation.
 Have higher oxidative potential or inhibit free radical-
induced drug decomposition.
E.g. Ascorbic acid, sodium bisulfate, sodium formaldehyde,
sodium meta bisulfite
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D. Buffers and pH adjusting agents:
 A buffer resists changes in PH upon addition of an acid or
base.
 It is composed of a weak acid and its conjugate base or a
weak base and its conjugate acid.
 Buffers are added as pharmaceutical ingredient to:
 Increase comfort to the site of administration
 Render the formulation more stable
 Enhance the aqueous solubility of the drug
 Enhance the drug‘s bioavailability
 Maximize preservative efficacy
E.g. Potassium meta phosphate, Potassium phosphate,
monobasic Sodium acetate, Sodium citrate (anhydrous and
dehydrate).

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E. Viscosity inducing agents:
 Render preparations more resistant to flow suspensions,
ophthalmic solutions, topical creams and oral solutions.
E.g. Alginic acid, Bentonite, Carbomer, sodium carboxy
methyl cellulose, Sodium alginate, Tragacanth, glycerol
etc.
F. Emulsifying agents and Surfactant:
 Promote and maintain dispersion of liquid in another liquid
in which it is immiscible (Suspension and emulsion).
E.g. Tragacanth, Bentonite, Polysorbate 80, Accacia
G. Colorants:
 Colorants are added to impart color to liquid and solid
preparations

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 For esthetics and patient compliance
 For identification
 To minimize the medication errors
 To protect the contents of the formulation
E.g. Titanium dioxide, Calamine, Azo dye, Nitroso dyes,
xanthenes, Nitro dyes,
H. Flavorants and Sweeteners:
 Flavorants: Impart a pleasant flavor and often odor for
unpleasant or disagreeable taste, primarily to liquids
intended for oral administration.
 Sweeteners: Impart sweetness to the preparation.
E.g. Aspartame, Dextrose, Glycerin, Mannitol, Saccharin
sodium, Sorbitol, Sucrose
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I. Disintegrants:
 Overcome the cohesiveness imparted during compression.
 It increases break up → increase surface area → increase
dissolution → increase absorption
Eg. Starch, Alginic acid, Polacrilin potassium, Sodium
alginate, Microcrystalline cellulose
J. Lubricants:
 Reduce friction during tablet compression
 Enhance the flow of the material
 Minimize wear of the part of the machines
 Prevent fill material from sticking
 Produce tablets with sheen
E.g. Fine silica, magnesium stearate, Talc
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k. Adhesives or Binders:
 Promote adhesion in Granules and tablets.
E.g. Acacia, Alginic acid, Carboxymethylcellulose sodium,
Compressible sugar, Ethylcellulose, Gelatin, Liquid
glucose, Methylcellulose, Povidone, Pregelatinized starch,
dibasic calcium phosphate, polyvinyl pyrollidine.
L. Other pharmaceutical ingredients:
 Ointment bases: Parts of an ointment which is used as a
Vehicle
 Suppository bases: Vehicles for suppositories
 Gelling agents: They are ingredients that give the
preparation a gel like consistency.
E.g. Tragacanth- bassorin pastes, Sodium alginate,Pectin,
Starch. 47
 Diluents or Fillers: Create tablet of proper size and
consistency.
• Added when quantity of AI is small or difficult to compress
 Packaging and pre-pack of pharmaceutical products

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