Introduction to Compounding
 Compounding in Pharmacy refers to the special preparation of
drug products that are uniquely tailored to a patient’s needs
medically and otherwise.
 Extemporaneous is often an adjective that describes this unique
characteristic of compounding.
 What is compounding?, what is Manufacturing?
 According to the FDA, compounding is
 Made to dispense a product on the basis of a Rx for a specific
patient’s needs
 Pharmacist can not compound a copy of a commercial available
product
 Pharmacist can not sell his/her product without an Rx
 Can’t advertise the product (i.e. they can advertise their
compounding service but not the product itself)
Extemperaneous Compounding
 Pharmacy makes a unique product dose form for a
specific patient, i.e acetaminophen 2% cream
 USP 795 says that expiration dating for these products
should not exceed 25% of the time remaining among
the manufacturer drug product or six months into the
future which ever is earliest
 Any product where water is add to a solid dosage form
is given 14 days under refrigeration unless published
data state otherwise
 Compounded items can be: creams, ointment, solutions,
suspensions, intravenous solutions, capsules, suppository, etc.
 Solutions are homogenized mixtures of drug in aqueous medium.
 Suspensions are heterogeneous mixtures of a drug in aqueous
medium. These mixtures often require the shaking of the drug
before the suspension can be given.
 Intravenous solutions are aqueous drug mediums that are free of
particles; they are sterile and pyrogen free
 Capsules are oral dosage forms that are enclosed in a gelatin casing
that dissolves in the stomach and small intestine
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Gelatin capsules come in sizes from 000 to 13.
00o is the largest size
13 is the smallest size
 Suppositories are dosage forms that are applied rectally. They are
usually made of material like glycerin which melts at slightly below
body temperature. Used for patients that can’t swallow due to
neurological disorders (dysphagia)
Special Compounded Dosage
Forms
 Emulsions are mixture of two non mixable liquids in a
stabilized medium. Normally, oil in water do not mix;
however, a compound can be made (an emulsion)
where the two liquids can be “mixed” with each other.
 Examples in pharmacy are creams and lotions.
 Examples in food are mayonnaise and milk (fat mixed
in water)
 Two types of emulsion are oil in water (o/w) or (w/o)
References for Compounding
 Remington’s Pharmaceutical Sciences
 Trissel’s Stability of Compounded Formulations
 Drug Facts and Comparisons
 United States Pharmacopeia
 The International Journal of Compounding
Pharmacists
Compounding Equipment
 A more complete list is mention in the text
 The more important ones are following
 Balance, class A, required in every pharmacy by the state
board
 Beakers
 Filter papers
 Graduated cylinders
 Hotplates
 Molds
 Mortar and pestle
 Ointment slab
 Spatulas
 Weighing paper
Mortar and Pestle
 Very important in compounding
 represents a symbol of the pharmacy profession. Shown as
 Used to comminutate or triturate a substance to smaller
particle sizes. Smaller particle sizes are a key to make
certain compounds more appealing to the touch and taste.
 Glass mortar is used to mix liquids with powder and
porcelain is used for granular powders
Solutions
 Aqueous or Hydroalcoholic mixtures that are solvents
for homogenized solute/solvent system
 Solute : drug that is mixed into the system
 Solvent: the vehicle or medium used to carry the solute
 Solvents include:
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Purified water USP: contains no more than 10 ppm solids
Sterile water for injection USP: same as purified water except
for sterility and pyrogen free state: used to mix IV drugs
Sterile water for Irrigation USP: used to make oral solutions
 Types of solutions
 Simple Syrup USP: 85% w/v sucrose in water.
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Excellent vehicle for a sweeten drug dosage form for children
Self Preserving: no antibacterials
 Elixirs
 Water and alcohol cosolvent systems
 Typically as some sugar also
 Usually about 10%w/v to 40% w/v alcohol
 Aromatic Waters
 Mixture of water, alcohol, and a volatile oil
 Jasmine water is water, alcohol and jasmine oil
 Spirits or Essence
 Mixture of water, alcohol and volatile oil where alcohol content is 50% to 90%
 Tinctures
 Hydroalcoholic mixtures where concentration of drug is 10%
 10% is the concentration of the whole plant source; 1% is the active drug
 Ie. Opium Tincture is 10% in opium and 1% or morphine
Characteristics of Solutions
 Benefits
 Provides an easy way to measure doses for small patients
and babies
 Provides a way to increase bioavailability of the drug
 Drugs can be sweeten and flavored to mask bad taste
 Disadvantages
 Bulky dosage form
 Susceptible to hydrolysis with water
Suspensions
 Heterogeneous mixture of drug into a medium that
normally it does not dissolve in.
 System consists of water, drug powder, sweetener,
flavorants, colorants and an agent called an surfactant
which “thickens” the medium to allow particles of drug
to remain “suspended”
 In systems with no surfactant the drug particles quickly
settle to the bottom and aggregate.
 Surfactants allow the system to be uniform long enough
to measure a dose
 “Shake before using” is normally require as an auxiliary
label
Surfactants
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Acacia
Methylcellulose
Carboxymethylcellulose
Xanthan gum
Carrageenan
Amylopectin
Bentonite magma 5% (exhibit thixotropy: gels on standing
and liquefies on shaking)
 Other name for surfactants are Suspending agents
 A Common commercially available suspending agent is
OraPlus ®
Emulsion
 A pharmaceutical system where two immiscible liquids are mixed
together to form a stable system
 Normally two immiscible liquids like water and canola oil don’t mix
and the less dense oil beads to the top
 Purpose of Emulsion
 Increased drug stability (drug that under hydrolysis in water may be
more stable in emulsion)
 Better applicability in topical administration
 Two phase of the emulsion
 Internal phase- the dispersed liquid
 External phase-the dispersion medium liquid
 If water is the dispersed liquid you have a w/o emulsion
 If oil is the dispersed liquid you have a 0/w emulsion
 The type of emulsion formed depends on the phase volumes and the
type of surfactant or emulsifier used to stabilize this system
Emulsion Types
 A classic o/w emulsion is vanishing cream
 A classic w/0 emulsion is a lotion
Emulsifying Agents
 Emulsifier or surfactants are agents that stabilize an
emulsion.
 As emulsions age, they destabilize and separate in two
phase (i.e. milk that is old separates). This is called
cracking and means the emulsion is destabilized
 Emulsifiers can be natural or synthetic
 HLB (hydrophilic Lipophilic Balance) Scale is measure
of what type of an emulsion is created when used a
given emulsifier
 HLB<9 tend to form w/o
 HLB>9 tend to form 0/w
Emulsifier
 Natural
 Acacia
 Tragacanth
 Agar
 Methylcellulose
 Carboxylmethylcellulose
 Synthethic
 Sodium Lauryl Sulfate medium HLB
 Sorbitan esters (Spans) low HLB
 Polysorbates (Tweens) high HLB’s (o/w)
Popular non medicated Emulsion
bases
 Alamay Base
 0/w
 Vanishing cream (moisturizer)
 Cetaphil
 0/w
 Non soap cleaner
 Eucerin
 w/0
 Moisturizing cream
 Keri Lotion
 0/w
 Moisturizing cream
Ointment Bases
 Ointment are semisolid mixture of a drug (in liquid)
incorporated into a oily stiffen base.
 Oleaginous base
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Petrolatum is a high hydrocarbon mixture base used to carry water
insoluble drug into the skin
Petrolatum is not washable and can’t absorb any water
Forms occlusive layer and used as an emollient
For example : Vaselin ®
 Absorption base
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Can absorb water
Hydrophilic Petrolatum (Aquaphor ®)
 Water soluble base
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Can absorb water
Can wash easily with soap and water
Consists of PEG 3350 and PEG 400, which are water soluble bases
 Propylene glycol-ethanol systems when mixed with 2%
hydroxypropyl cellulose forms a clear gel
 A gel is emulsion system where a solid is the dispersed
phase and water is dispersion medium
 Exhibit thixotrophy: shaking and agitation causes the
honey like substance to flow more easily (like water)
 Absorbs considerable water into the gel “sponge effect”
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Used in wound care to sieve pus
 Incorporation of drug into ointments or emulsions involves the
following:
 Comminution
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Break down and crushing solid particles into smaller particle sizes to
increase its surface area
 Trituration is comminution by frictional shear force (rubbing)
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In practice comminution is done in a porcelain wedgewood mortar and
pestle
 Levigation is the process of increasing particle size by an a small
amount of mineral oil to the reduced drug powder. This act “wets”
the powder
 The drug/levigating oil mix is then incorporated into the base when
heated to near molten state (Fusion method)
 Alternatively the drug/oil mix is incorporated little by little into the
base via geometric dilution on an ointment slab
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Geometric dilution
PLO Organogel System
 PLO Organogel Systems are o/w type emulsion system
 Has excellent skin penetration ability
 Drugs can be incorporated into the organic phase or
the aqueous phase
 The organic phase is a lecithin emulsifier
 The aqueous phase contains a poloxamer polymer in
water
 PLO stands for Pluronic Lecithin Organogel. Pluronic
is the trade name for poloxamer(s) compounds which
were synthesize for the first time in the 1970’s
Prepacking and Unit dose systems
 Helps in inventory management in hospitals
 Prepacked and unit dose blister cards by law are permitted to be return to inventory upon
return
 Beyond use dating BUD are one of two systems
 50% of the expiration date on the manufacturer drug or 1 year whichever is sooner (my
hospital uses this)
 25% or six months whichever is sooner
 State and Federal regulations requires that the following is present on the prepackage
label (at a minimum):
 Name, dose, and dosage form of drug
 Internal lot number of drug AND manufacturer’s name and lot
 BUD (not manufacturer’s exp date)
 The master record file must contain:
 Drug, dose, dose form
 Manufacturer’s name, lot number, expiration date
 Internally assigned lot number
 BUD
 Date prepacked
 Quantity prepacked in this batch
 Technician initials
 Pharmacist’s SIGNATURE
Medications that should not be
prepacked (unit dose)
 The standard unit dose prepackage machine as a mechanical dial that rotates
between metal plates that are heated to high temperatures. Oral dose forms
are placed on the dial and the metal plates seal the blister pack material around
the medication with heat
 Some medications should not be prepacked with a standard machine because
the machine will become contaminated with dust particles from these drugs
 At times a dedicated machine can be used for some of these drugs
 Common highly allergic potential drugs include:
 Penicillins, Cephalosporins, sulfa drugs
 Moisture Sensitive medications
 HIV medications
 Praxada ®
 Pyridostigmine (Mestinon)
 Prasugrel (Effluent)
 Emtriva
 Most orally melting tablets : Risperdal M
 Capsules
 Most gelatin capsules will melt when exposed to heat
 Ritonovir
 Omega 3 Fatty Acids capsules
 Chemotherapy drugs and Teratogenic drugs
 Chlorambucil (Leukeran)
 Cyclophosphamide (Cytotaxan)
 Cyclosporin (Gengraf)
 Bosentan (Tracleer): Pregnancy category X
 In general, always inquire about the pregnancy rating and the cytotoxic
potential of drugs before you are asked to prepack anything. (especially
if you are a woman of childbearing potential)
 For a more complete listing visit:
 http://www.ashp.org/s_ashp/docs/files/MedNO_unit-
dosedpackage.pdf
Introduction to Sterile Products
 A sterile product is a product that is free of
contamination, microorganism free, and pyrogen free
 Examples of sterile products are intravenous products
(IV), ophthalmic products (for the eye), and nasal
products (for the nose), Intramuscular (into the
muscle) and subcutaneous (under the skin)
 Aseptic technique refers to the procedure of properly
performing the preparation of sterile products.
 Includes the environment, equipment, and personnel
garb
 Provides guidelines for the procedure
 Normally any agent that bypasses the skin or the
gastrointestinal tract must be both sterile and pyrogen free.
This is because the skin and the GI tract have a protective
role in filtering out damaging foreign substances or
microorganisms.
 The blood is a sterile body fluid that requires sterile drug
products. Blood is filtered by the spleen and then by the
lymph nodes as its becomes lymph; however, when a drug
is introduced directly into the blood it must be sterile.
 Consequences of contaminated IV products can be serious
 Most IV drug products are contaminated by touch
contamination.
 Bacteria, fungus, and other microorganism colonize the
skin
 Common skin microorganisms are: Candida,
Dermatophytes, and Staphylococcus bacteria. Others
are common as well.
 Contaminated products can “colonize” the blood and
produce bacteremia and fungemia. Infections can
evolve into septic shock and death.
 Watch :
http://www.youtube.com/watch?v=KC8qgxNB2FA
Environment for Sterile Products
Preparation
 Class 100 environment is an environment that has air that
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contains no more than 100 particles (0.5 microns) or larger
in one cubic foot of air.
Laminar flow hoods provide this environment.
Horizontal flow hoods filter air and pass it through a HEPA
filter and outward out of the hood.
Vertical flow hoods blow filtered air down towards the
surface of the hood.
Biological Safety Cabinets are vertical flow hoods that pulls
air through vents in the front and back of the hood to
prevent the preparer from receiving this air. It is used to
make chemotherapy drugs.
USP 797
 Introduced in 2004 by the US Pharmacopeia.
 Consists of standards for the environment to be
considered in the preparation of sterile products
 Endorsed by JCAHO and other regulatory agencies
 Followed in most hospitals with others moving towards
compliance.
 Standards include wall/ceiling, wall/wall and wall/floor
junction specifications, etc
 In general, sterile products are prepared in laminar
flow hoods in similarly compliance air quality rooms
 Such rooms are called “clean rooms”
 Usually have partitions that separate areas of the room
for storage of IV products, gloves, and needle and
syringes
 Rooms are usually positively pressurized to “push”
contaminates out and to keep other particles from
being pulled in.
Other Sterile Product Equipment
 Needle are sterile puncturing devices meant to access drug
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solutions in vials and to administer drugs to patients.
Normally are 3/8 of an inches to 3.5 inches in length
The diameter, or bore, of the needle is determined by its
gauge.
The larger the gauge the smaller the bore of the needle
In general, 25 or 27 gauge needles are under for
subcutaneous injections, 22 gauge for IM injections with 18
gauge and 16 gauge meant for pharmacy compounding of
IV products. 13 gauge is typically the larger bore needle you
will find.
 Syringes are the containers that hold the drug solution
after its been drawn from a vial.
 Consists of a tube with graduations marks, a piston, a
plunger with grip collar and at the other end a luer lok
tip (most syringes).
 This luer lok tip is designed to be a twist on to
attached to a needle or to a injection port on a catheter
to administer an injection
Author: William Rafti of the William Rafti
Institute from Wikipedia
Source: wikimedia commons page
Intravenous Solutions
 Normal saline (0.9%) is one of the most common because its isotonic
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with plasma. Isotonic means equal to it in terms of “tonicity”. i.e.
plasma has a tonicity valve of about 290 mOsm. Normal saline or NS is
about 300 mOsm.
Tonicity of a solution determines if bodily fluid shifts will occur
Dextrose 5% in water (D5W) is the second most common type.
Consists of glucose or dextrose in water to make it 285 mOsm
(isotonic)
D5WNS is a combination of the two and is used when some calories in
the form of glucose is needed. Hypertonic (580 mOsm about) but it is
Ok to use.
3 % Saline (NaCL) is only used to treat certain brain conditions. Very
hypertonic and can cause death if used improperly
23.4% saline (NaCL) used only in certain rare conditions and in small
volumes. Will cause death if used improperly (remember Emily Jerry?)
Type of IV therapy
 IV primary infusion consists of a drug that is given
continuously through a large volume parenteral
solution
 IV Piggyback is a IV administration of a drug that is
normally piggybacked to another primary IV via a Y
site connection on the primary IV tubing.
 IV Piggyback sets are designed to be small in volume
usually 50 ml to 100 ml and are hung above the
primary bag on the IV pole. (see next page)
 Rate of infusion can be controlled by gravity and a
roller clamps or by an electronic pump
Picture of IV Piggyback set up
A word about filters
 At times a filter is needed to filter IV solutions
 i.e. when breaking an ampule you need to use a filter
needle to draw the solution to prevent glass particles
from entering the IV.
 A 0.22 micron filter is a special filter that is called a
“sterilizing” filter that can sterilize a fluid as it is
passed through the filter.
Compounding Vocabulary
 Terminology for compounding and dosage forms that may be on the
exam
 Mucilages are mediums that are similar to suspensions in that the drug
is suspended into the medium. (Metamucil®). Magmas and milks are
in this category
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Suspensions of high viscosity
 Extractives
 Tincture is a hydroalcoholic extractive of a drug where the potency of drug is
equal to 100 mg of the crude ingredient per ml. i.e. Tincture of Opium 1 ml
contains the equivalent of 10 mg morphine (this is how much morphine is in 100
mg of crude opium poppy)
 Fluidextracts are 10x the potency of tinctures
 Troche
 A lozenge or dosage form meant to dissolve in the mouth
 Pellet
 A solid cyclindrical dose form that is planted subcutaneously for slow absorption
 Powders
 Finely divided powders that are given internally
(swallowed) or topically. Usually dispensed in pouches
called “powder paper”
 Suppositories
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Dosage form given into the rectum, vagina, or urethra for local
or systemic drug effects
Common excipients are glycerin or cocoa butter
 Enema
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Dosage form that can be rectally for local effect
 Collodion
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Mixture of alcohol and water with pyroxylin
Applied topically (poison if swallowed)
Liquid Bandages
 Comminution
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Reduction of gross particles to granular powder (crushing)
Trituration is reduction of particles sizes by rubbing and friction
heating
Both comminution and trituration occur in a wedgewood mortar
 Levigation
 Add a small amount of solvent to a powder to increase the
surface area for mixing
 Pulverization by Intervention
 Adding a small amount of votalite solvent to a granular
powder to aid in trituration. As trituration proceeds the heat
of friction causes the finely divided powder to be left behind
as the solvent evaporates.
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camphor crystals mixed with alcohol
 Geometric Dilution
 Technique used in the mixing of two unequally sized
ingedients
 Typically involves ointment or creams on an ointment
slab
 Small quantity is measure against an equally sized
quantity from the larger ingredient and mixed
 The mixture is now measured against an equally sized
portion from the larger ingedient and mixed
 This process continues until both ingedients are
incorporated into a single product