Pharmacist's Letter

Online Continuing Education and Webinars

Non-Sterile Compounding for the Community Pharmacy:

Topical Preparations and Oral Liquid Dosage Forms
Volume 2012, Course No. 315
Self-Study Course #120315
Compounding Best Practices: Topical Preparations | Compounding Best Practices: Oral Liquid
Preparations | Calculations and Conversions
Preventing Errors | Test Your Knowledge | Wrapping It Up
References

Lisa drops off a prescription for a compounded topical

product (sildenafil 1% topical cream).
You find the following recipe and know that all the
ingredients are stocked in your pharmacy.
Sildenafil citrate tablets 1 g
Propylene glycol 10 g
Oil-in-water emulsion base qs 100 g
Do you feel comfortable making the compound?
Pharmacy compounding helps fill the gaps when commercially available
products don't fit the bill. This can occur for a variety of reasons in the
community setting, including lack of availability of a specific dose (e.g.,
small doses for pediatric patients, high concentrations of analgesic drugs
for chronic pain patients) or lack of availability of a specific dosage form
(e.g., liquids for patients who can't ingest tablets or capsules, topical
formulations of drugs that can have a local effect). For additional
information, get our Technician Training Tutorial
Compounding.
Oral liquids and topical preparations are two of the most commonly
requested types of pharmacy compounds in the community pharmacy
setting. This continuing education review provides basic information on
compounding topical products and oral liquids, along with some sample
problems to test your knowledge.

Compounding Best Practices: Topical

Preparations
Question
#1
Pharmacy
Compounded topical preparations
include creams,
compounding
is a gels, lotions,
ointments, and pastes. These canway
be relatively
simple
to prepare on a
to
small scale for pharmacies that have
somepatients
basic compounding equipment
a. help
and supplies available.
save money.
b. meet patients'
Have the different formulations
of topical
products
needs when
a
caused confusion? Can you
describe
the
differences
suitable product
between formulations andiswhen
not they might be used?
Get our Technician Training
Tutorial
commercially
Dosage Forms.
available.
c. provide
products that
Definitions
have been
discontinued by
Cream: an opaque soft
solid
thick liquid intended
FDA
fororsafety
reasons.
for external application.
Can have a drying effect.
d. maximize
reimbursement
Gel: a semisolid system
consisting of a suspension
for the particles or large organic
made up of small inorganic
pharmacy.
molecules interpenetrated
by a liquid.

Lotion: a fluid emulsion or suspension for external

application. Can have a lubricating effect.

Ointment: a semisolid preparation intended for

external application to the skin or mucous membranes
that softens or melts at room temperature.

Paste: a thick, stiff ointment that ordinarily does not

flow at body temperature. Can be used as a protective
covering.

Considerations for Preparing Topical Creams and Lotions

Creams and lotions are both emulsions. They can be of either the waterin-oil type (e.g., water insoluble, not water-washable, occlusive, greasy)
or oil-in-water type (e.g., water soluble, water-washable, non-occlusive,
non-greasy).1
Definition
An emulsion consists of one phase dispersed in a second

phase, by an emulsifying agent.

Whereas creams can have a drying effect, lotions can have a lubricating
effect. Creams of the oil-in-water type can often be made into lotions,
through the gradual addition of water or an aromatic water, like rose
water.1,2
Common Ingredients of Creams and Lotions
Common active ingredients in compounded creams include retinoic acid,
triamcinolone, and urea. Preparation of creams and lotions (or any
emulsion) typically involves input of energy to break up and disperse one
liquid in another (for example, mechanical agitation via mortar and pestle
or simple shaking via the "bottle method").
Have you ever wondered why ingredients for a compound
must be mixed together in a specific order? Have you ever
compounded a product and wondered why it wouldn't go into
solution or couldn't be incorporated into a cream?
An emulsifier (e.g., acacia, glyceryl monostearate, polyethylene glycol
[PEG], sodium lauryl sulfate, Spans
make a cream or lotion. Emulsifying agents help make two immiscible
liquids more miscible, or rather, help distribute one phase more evenly
and finely though another.1
Emulsifying agents are "rated" on the arbitrary numeric hydrophilelipophile balance (HLB) system. Agents with a lower HLB value are
more oil-soluble, and those with a higher HLB value are more watersoluble. The value of ten is considered to be the breaking point between
oil- and water-soluble. An emulsifier that's oil-soluble is appropriate for
preparing a water-in-oil emulsion, whereas an emulsifier that's watersoluble is appropriate for preparing an oil-in-water emulsion.
For example, glyceryl monostearate has an HLB value of 3.8. It would be
best for a water-in-oil emulsion like
an HLB value of 12. It would be best for an oil-in-water emulsion like
Dermabase. Often, more than one emulsifying agent is used to prepare an
emulsion so all ingredients are properly mixed.
HLB values for substances can often be found in compounding references
and texts, several of which are listed in the reference section of this
continuing education review.
A levigating agent, like mineral oil or glycerin, or a wetting agent, like

alcohol, might be needed when anQuestion

active ingredient
is being incorporated
#2
into a prepared or commercially Which
available
cream base. The wetting agent
of the
helps increase contact between solid
particles
and liquids. Levigating
following
agents help reduce particle size. statements
Decreasingare
particle size helps the
ingredient be evenly mixed throughout
the
base.
TRUE concerning
the use of
Some commercially available cream
bases include
compounded
Vanicream (both oil-in-water) and
products?
in-oil). It's important to use the correct
base when
a. Creams
are compounding so the
ingredients are properly incorporated.
often used as
lubricants.
Definitions
b. Pastes can be
used as a
Levigating agent: "aprotective
liquid used as an intervening
covering.
agent to reduce the particle
size of a drug powder by

c.
Lotions
grinding together, usually in a mortar and pestle." The
be used with the base, and
levigating agent mustshould
be compatible
when
a
the substance to be levigated product
should not be soluble in
must be
the liquid.3
insoluble in
Wetting agent: "aidswater.
in attaining intimate contact

d.
Ointments
between solid particles and
liquids."
should not be
applied to
mucous
In the sildenafil topical
cream example, the
membranes.
propylene glycol would be used as a levigating
agent.
Equipment for Preparing Creams and Lotions
What equipment do you use to make creams
and lotions in your pharmacy?
To prepare a cream base, which is an emulsion, a liquid phase will need
to be dispersed, or broken up. This can be accomplished manually, with a
glass mortar and pestle, or with an electric mixer, hand homogenizer, or
shaker.1
When active ingredients are being incorporated into a prepared or
commercially available cream base, a pill tile and spatula might be
necessary. Avoid using ointment papers because they can tear when they
become moist. Measuring devices might also be required, like a
prescription balance and graduates.

To learn more about compounding terms and

equipment that's used, get our
Principles of Non-Sterile Compounding for the
Community Pharmacy
Compounding Techniques for Creams and Lotions
The wet gum (English) or dry gum (continental) method can be used to
prepare an oil-in-water emulsion. The wet gum method involves the use
of a gum (like acacia, for example) dissolved in water (hence, wet gum).
The oil is added gradually, and then more water is slowly added. The dry
gum method involves mixing a gum rapidly with oil, and then adding the
water all at once with rapid trituration.
Definition
Trituration: the process by which an ingredient is ground in a
mortar and pestle in order to reduce particle size. This term
may also refer to the mixing of two or more drug substances
with a mortar and pestle.
The bottle method is similar to the dry gum method, except the
ingredients are shaken in a bottle instead of mixed in a mortar and pestle.
The beaker method is another option for preparing an emulsion. Both the
oil and water phase are gently heated, and then the internal phase is added
to the external phase with constant stirring.
When the active ingredient is being incorporated into the prepared or
commercially available cream base, it's important that the particle size is
very fine. The particles should be crushed into a fine powder of uniform
size. You shouldn't see any large pieces that haven't been completely
crushed. This will prevent any gritty feel, which could irritate the skin.
Let's look again at the sildenafil cream example. In order to
get the tablets into solution so they can be evenly distributed
in the emulsion base, they would need to be triturated. This
would be accomplished by using
a mortar
Question
#3 and pestle to grind
the tablets into a fine powder. After levigating with propylene
A patient calls
glycol, you can combine all the ingredients on a pill tile using
your pharmacy
a spatula. Avoid using ointment papers since the water in the
saying the
cream may cause the paper to tear.
compounded
cream they
Other Considerations for Creams
and picked
Lotionsup
recently
doesn't seem right.

Beyond-Use Date

It seems gritty and

doesn't spread as
The beyond-use date for most creams
and as
lotions
smoothly
it has(if they contain water
and are prepared from solid dosage
forms)
be 14 days when stored in
in the
past.will
Which
the refrigerator at "cold temperatures"
(e.g., between 36 and 46 degrees
of the following
Fahrenheit). This can be extended
if there
scientific stability data for
may
be theare
cause
support.1
of this?
a. Ingredients
Some physical signs of instability of
creams
and lotions include breakage
from
a different
of the emulsion, crystal growth, shrinkage
caused
manufacturer by evaporation of
water, and gross microbial contamination.
may have a
different texture.
USP Requirements for Beyond-Use-Dating
b. The cream
may
be past
its
These are general rules that apply
to most
non-sterile
dosage forms:
beyond-use
Solid and non-aqueous date.
(non water-containing) liquid
c. The patient
preparations:
didn't
thoroughly
o If the source of active
ingredient is a manufactured
shake
the
product:
product before
applying it.
Not later than 25% of the time left on the
d. Theexpiration
wet gum date, OR 6 months
manufacturer's
method
may
from the day
the compound
is made
have
been
used
(whichever is sooner).
during
compounding.
o If the source of active
ingredient is a USP or NF
product:

Not later than 6 months from the day the

compound is made.

Aqueous (water-containing) liquid preparations

o If the source of active ingredient is a solid dosage
form (tablet, contents of a capsule, etc)

Not later than 14 days from the day the

compound is made if the preparation is stored
under refrigeration (between 36 and 46 F).

All other preparations

o Not later than the intended duration of therapy OR 30

days from the day the compound is made (whichever
is sooner).

Auxiliary Labels
Use the following auxiliary labels for most compounded creams and
lotions:

Refrigerate

External use only

Shake before using (lotions only)

Since the sildenafil cream is compounded in an oil-in-water
emulsion base, give it an expiration date of 14 days. This
could be extended if there is information to support a longer
stability. You'll also want to be sure to include auxiliary labels
for refrigeration and external use only.

Considerations for Preparing Topical Ointments and Pastes

Ointments and pastes can be good for hydrating the skin, and for
protecting the skin.1
There are different types of ointments. There's the oleaginous ointment,
which is insoluble in water. White petrolatum and white ointment are
both examples of oleaginous ointment bases. The absorption ointment is
also insoluble in water, but can absorb water.
examples of absorption ointment bases. Water-soluble ointments absorb
water, but are non-occlusive and non-greasy. An example of a watersoluble ointment base is polyethylene glycol ointment.
Common Ingredients of Ointments
Generally, preparing an ointment will involve incorporating active
ingredients into prepared ointment bases, like the examples given above.
A levigating agent is often necessary. Mineral oil works well with
oleaginous ointment bases. Depending on the formulation, water,
glycerin, alcohol, propylene glycol, or mineral oil can be used as
levigating agents with absorption bases. Polyethylene glycol and

propylene glycol are good for incorporating

insoluble powders into waterQuestion #4
soluble bases. Water or glycerin When
can also
be used with water-soluble
preparing
bases.1
topical dosage
forms, reducing
Equipment for Compounding particle
Ointments
size of an
active ingredient is
Small amounts of ointment can be
preparedtoon a pill tile or ointment slab,
important
with a spatula. Ointment papers
may
also it
bemix
used, but you must be
a. help
careful not to tear these or the paper
will with
become
better
the mixed with the
ointment, requiring the compound vehicle.
to be destroyed. A balance may be
required for measuring ingredients. A mortar and pestle may be required
b. prevent the
for particle size reduction. (Particle size reduction is important for
finished product
ointment preparation, to avoid a gritty feeling, which could be irritating to
from feeling
the skin.)
gritty and
irritating the
Ointment mills can also be used for preparing ointments.
skin.
c. improve
A water bath might be helpful in
preparing
ointments that require gentle
stability of the
1
heating of some ingredients.
product.
d. improve
Compounding Techniques for
Ointments
product taste.
Often, compounding an ointment will require reducing the particle size of
Question
#5 ingredient with a small
the active ingredient(s) and levigating
the active
Which
amount of the base or other liquid.
The of
restthe
of the ointment base can then
following
is
TRUE
be added using geometric dilution to ensure the
active ingredient is
1
regarding
evenly distributed.
compounded
topical dosage
Definition
forms?
Geometric dilution helps ensure that an active ingredient is
a. Creams can
evenly distributed through a vehicle. "Geometric dilution
sometimes be
involves a series of dilution steps. It begins by incorporating
made into
the drug into an amount of ointment of approximately the
lotions.
same size. Then, a second amount of ointment approximately
b. Ointments
equal to the first mixture is added and mixed. This stepwise
should usually
dilution process is continued until all of the ointment has been
be refrigerated.
used."4
c. Using
geometric
What auxiliary labels would
you put
on compounded
dilution
helps
topical products? How might
thethat
labels
ensure
the differ for each
specific formulation (ointment,
gel, etc)?
active ingredient
is evenly
distributed
Other Considerations for Compounding
Ointments
throughout the
vehicle.
Beyond-Use Date


d. Both A and C
Generally, a 30-day beyond-use date should be assigned for ointments
that do not contain water. For ointments that do contain water and no
preservative, no more than a two-week
supply
Question
#6 should be dispensed.
Which of the
Ointments should generally be kept
at room temperature. Some physical
following
signs of instability of ointments statements
include change
is in consistency and
separation of liquid, formation ofTRUE
granules
or
grittiness, and drying.
regarding
the preparation of
Auxiliary Labels
topical gels?
a. The use of
Label ointments with "External usewetting
only." agents
should be
Considerations for Preparing Topical
Gels
avoided.
b. Gels should
Gels are a type of suspension. Gels can be either organic (e.g., carbomer,
appear separated
tragacanth) or inorganic (e.g., aluminum hydroxide, bentonite magma),
after sitting for
depending on the type of particles that are suspended. They can be either
24 hours.
one-phase (homogenous) or two-phase (heterogenous) systems. They can

c. Gels
be aqueous, alcoholic, or oleaginous,
or prepared with a base of water,
containing
alcohol, or oil. Some gels can actually
serve aswater
ointment bases.
will typically
have a 14-day
Common Ingredients of Gels
expiration date.
d. Gels
cannot
Common gel-forming agents include
acacia,
alginic acid, bentonite,
be
aqueous.
carbomer, carboxymethylcellulose, gelatin, guar gum, and xanthan gum,
among others. In some cases, a wetting agent, like glycerin, may be
Question #7agents.
required to prevent clumping of gel-forming
of instability
commercially available gel baseSigns
for topical
use.
of compounded
Equipment for Compounding topical
Gels products
include
Measuring devices, like a balance
graduates, may be needed for
and
a. Precipitation
preparation of gels. Particle size reduction
of or
the active ingredient might
of crystals
be required, which would necessitate
the use of a mortar and pestle or pill
granules
tile and spatula.
b. Separation of
liquid
Compounding Techniques for
Gels
c. Discoloration
When gels are prepared, the gelling
typically added to water.
d.agent
All ofisthe
Then, the active ingredient can be added.
Sometimes,
the drug is actually
above
added prior to the gelling process. This is okay if the active ingredient
does not interfere with the gelling process.
Other Considerations for Compounding Gels

Beyond-Use Date
Generally, water-containing gels should have a beyond-use date of no
more than 14 days when stored at cold temperatures, such as in a
refrigerator. This can be extended if there are scientific stability data for
support.1
Some physical signs of instability of gels include shrinkage, separation of
liquid, discoloration, and gross microbial contamination.
Auxiliary Labels
Label most topical gels with "External use only" and "Refrigerate."
In what situations might an oral liquid need to
be compounded for a patient?
Compounding Best Practices: Oral Liquid Preparations
Oral liquids are a relatively common compounded dosage form. The
compounding of oral liquids is important for patients who require oral
drug therapy, but are unable to ingest commercially available dosage
forms (e.g., pediatric patients, the elderly, patients with enteral feeding
tubes). Compounding oral liquids is also a way to facilitate the use of
dosages that aren't commercially available.
Oral liquids include both solutions and suspensions.
Definitions

Question hydroalcoholic
#8
"Elixirs are clear, sweetened,
Which
of thesolutions that are
(containing water and
alcohol)
following
usually flavored and
are suitable for drugs that are
statements
are in water-alcohol
insoluble in water alone
but soluble
mixtures. They areTRUE
usuallyconcerning
less sweet and less viscous
(thick) than syrupsthe
andcomposition
are generallyofless effective in
oralmay
liquids?
masking taste. Elixirs
contain different solvents
a.e.g.,
Elixirs
are alcohol, glycerin,
as co-solvent systems,
water,
more and
viscous
sorbitol, propylene glycol
polyethylene glycol
than syrups.
300."1
b. Suspensions
"Oral liquids are intended
for oral administration and
serve as
pleasant-tasting
contain one or more substances
with or without
for agents dissolved in
flavoring, sweeteningvehicles
or coloring
active drug.
c. Suspensions

contain the
active
drug in an
water or cosolvent-water
mixtures."
insoluble form.
d.
Solutions: Solutions
areSyrups
liquid and
preparations containing
suspensions
are
one or more drug substances molecularly
dispersed in
both
types
of
a suitable solvent or mixture of mutually miscible
solvents.1 Syrups andsolutions.
elixirs are both types of
solutions.

Question #9
An elixir
a
Suspension: Suspensions
areissweetened,
flavored,
suitable
way
to
liquid preparations containing the active drug (or
prepare
a solution
excipients, when the
suspension
is prepared from
of
a
drug
that
is
commercially available drug products)
as insoluble
1

materials.
a. water-soluble.

b. alcohol"Syrups are concentrated,

aqueous preparations of a
soluble.
sugar or sugar substitute
with or without flavoring
c.substances.
either
agents and medicinal
Syrups can serve as
alcoholor drugs."
pleasant-tasting vehicles
for active
water-soluble.
d. waterinsoluble.
Considerations for Preparing Oral
Solutions

Oral solutions are prepared as either syrups or elixirs. The difference

between syrups and elixirs is that syrups can be used for drugs that are
water soluble, and elixirs are good for both water-soluble and alcoholsoluble drugs. The reason for this is that elixirs are mixtures of alcohol
and water. (Syrups sometimes contain alcohol, but at a very low
concentration).1
Common Ingredients of Oral Solutions
There is a long list of commercially available vehicles for syrups. These
include cherry syrup; Ora-Sweet
and wild cherry syrup. The pH (or measure of acidity) and alcohol
content of these vehicles varies, which
may #10
be the reason that one is
Question
preferred over another for a particular recipe.
Which of the
is TRUE
Equipment for Compounding following
Oral Solutions
to get a drug to
dissolve
into
For compounding solutions, a glass
mortar
and pestle is often needed. A
solution?
balance might be necessary to weigh dry ingredients. Measuring devices,
a. Heating
will
like graduates, are likely to be necessary
as well.
help a drug
dissolve
faster.
Compounding Techniques for Oral
Solutions

b. Larger
The most common way to make a solution
dissolve an active
particles isgotointo
ingredient in a solvent. This can usually
be more
accomplished by stirring.
solution
Sometimes, heat might be required.quickly than
smaller
When elixirs are made, the water-soluble
component is usually dissolved
particles.
in water, or the alcohol-soluble component
in alcohol. The
c. Addingisadissolved
drug
aqueous phase is added to the alcohol
solution.
This
way,
the highest
to a viscous
alcohol concentration possible is always
maintained.
Otherwise, the
solution
will
stability of the solution might be compromised.
make it dissolve
more quickly.
There's actually a long list of considerations
d. Stirringfor
willpreparing oral liquids.
Some of the more practical tips include
the the
following:
increase
amount of time
Small particles dissolve faster
thanfor
larger
it takes
a particles.
drug to dissolve
Stirring helps dissolve a drug
quickly.
intomore
solution.

Drugs will dissolve more slowly in a more viscous solution.

Increase in temperature will help a drug dissolve more quickly.

Other Considerations for Oral Solutions

Beyond-Use Dating
The beyond-use date for syrups prepared from solid dosage forms
shouldn't be more than 14 days from preparation, when refrigerated. The
beyond-use date for elixirs can be up to six months. These times can be
extended with scientific stability data to support.
Some physical signs of instability that apply for all oral liquids include
precipitation, discoloration, haziness, and gas formation resulting from
microbial growth.4
Auxiliary Labels
For many compounded solutions, you will use a "Refrigerate" sticker.
Flavor-Masking
As you might guess, one of the main complaints of parents who are
administering medications to children is the disagreeable taste.
masking can help make medications more palatable for young ones.
There are some basic techniques that
can be#11
used.
Question
A suitable flavor-

masking agent for

Bitterness can be complemented
with
an acceptable bitter flavor,
a drug that
tastes
would
be?
like coffee, chocolate, orsalty
maple.
Salty,
sweet, or sour tastes can
also be used to blend with
a bitter taste.
a. Vanilla
Objectionable tastes can
be masked with the cooling effect of mint
b. Butterscotch
and the anesthetizing effect of spices.

c. Coffee
Acids, like tartaric, citric, and maleic, can be used to enhance fruit

flavors.
d. Peppermint

Adding a little bit of saltiness may enhance the sweetness of a

Question #12
sour taste.
Besides flavormasking,
which
Note that suspending a bad-tasting
drug can
help.ofA drug that's not in
the following
canalso be used as the
solution cannot be tasted. A bad-tasting
drug can
help
reduce
a
internal phase of an emulsion, which is less likely to be in contact with
exposure
the oral mucosa than the externalpatient's
phase. High-viscosity
liquids, or those
to
the
bad
taste
of
that are thick, are likely to make the flavor linger in the mouth longer.
a drug?
a.
it as classes:
Consider using these flavors
forPreparing
specific drug
a solution
maple,
b. Preparing
it
Antibiotics: Cherry,
pineapple,
orange,
as
an
elixir
raspberry, banana-pineapple, banana-vanilla,
strawberry-vanilla c. Using a
viscous vehicle
to help
the currant, cherry,
Antihistamines: Apricot,
black
flavoring
(not
cinnamon, custard, grape, honey,
lime, peach-orange,
the
taste
of
the
raspberry, root beer, wild cherry
drug) linger in
the mouth banana-vanilla,
Barbiturates: Banana-pineapple,
d. Using heat to lime, orange,
black currant, cinnamon-peppermint,
dissolve the
peach-orange, root beer
drug into
solution more
Decongestants and expectorants
rapidly
black currant, butterscotch, cherry, strawberry, lemon,
maple, orange, orange-lemon, orange-peach,
#13tangerine
pineapple, raspberry,Question
strawberry,
Suspensions can
administered
by beer, wild
Electrolytes: Blackbecurrant,
lime, root
a
variety
of
routes.
strawberry
Which of the
following routes
MUST be sterile?
(And,
Use the following flavors
fortherefore,
masking basic tastes:

prepared only in a
cleanlime,
roomorange, cherry,
Acid/sour: Lemon,
environment as
grapefruit, raspberry
specified by USP
Chapter 797.)
Bitter: Anise, coffee, chocolate, mint,

grapefruit, cherry
a. Oral

Metallic: Berry, mint,

grape, marshmallow
b. Ophthalmic

Otic wintergreen
Oily: Peppermint,c.anise,

Topical
Salty: Nut, butter,d.butterscotch,
spice, maple

Sweet: Vanilla, fruit, grape, bubble gum, berry

It's important to consider how a flavoring agent can affect drug stability.
In fact, the product labeling for some commercially available oral liquids
gives information on which flavoring products should or should not be
used.
Considerations for Preparing Oral Suspensions
Suspensions are a good option when the drug for administration is not
soluble in a solvent (solution) or co-solvent (elixir) system.
can be administered by several different routes, including nasal (sterile
only), ophthalmic (sterile only), oral, otic,
topical. This discussion will focus on the preparation of oral suspensions.
Characteristics of a good suspension:

Settles slowly

Readily redispersed with gentle shaking

Prepared from small, uniform, particle-size powders

Pours easily from its container into administration devices

Question #14
Common Ingredients for Suspensions
An appropriately
compounded
A good suspending agent will have
the ability to maintain drug particles
suspension
in suspension (viscosity) but be fluid enoughwill
for easy pouring.
have which of the
following

Besides the active drug to be suspended,

a suspending agent is needed.
attributes?
Examples of suspending agents include
acacia, carbomer resins,
a. A beyond-use
methylcellulose, and tragacanth. These
agents
date of moreare mixed to specified
concentrations in order to serve as than
suspending
14 daysagents. Sometimes, a
flavoring agent is also needed.1
b. Easy to pour
In some cases, the suspending agent
already
be flavored.
c. will
Quick
settling
Commercially available suspending
agents
that
are
very commonly used
of suspended
for compounding suspensions include
particles
d. A pleasant
Equipment for Compounding Suspensions
taste
For compounding suspensions, a mortar and pestle, pill tile, and spatula
are commonly needed to reduce particle size of the active ingredient. A
balance might be necessary to weigh dry ingredients. Measuring devices,
like graduates, are likely to be necessary as well.
Compounding Techniques for Suspensions
Particle Size Reduction
A good suspension is prepared from small, uniform, particle-size
powders. Often, tablets or the contents of a capsule will need to be
triturated to reduce the particle size.
Wetting
Wetting involves gradually adding a wetting agent to the dry ingredients
of a suspension. The smallest amount of wetting agent should initially be
added to the dry ingredients to form a thick paste. Then, the vehicle can
be added, a portion at a time, with constant stirring, to form the
suspension.1
The wetting agent required to make a suspension can vary, depending on
the qualities of the dry ingredients (the active drug). If the drug is
hydrophilic or can be dissolved in water, a water-miscible liquid (water,
for example) can be used. If the drug is hydrophobic, a non-polar liquid
or surfactant (glycerin, for example) will be needed. Sometimes, the
wetting agent and the suspension vehicle are the same thing.
Other Considerations
Beyond-Use Dating
The beyond-use date for a suspension should not be longer than 14 days,
when refrigerated. With scientific stability data for support, the expiration

date may be extended beyond 14 days.

Auxiliary Labels
Like commercially available suspensions, label compounded suspensions
with "Shake before using." Many will also require a "Refrigerate" label.
Practical tips for preparing oral solutions and suspensions:

Don't "qs" with a stirring rod in the container of oral

liquid you're preparing. Once you take out the stirring
rod, you'll see that you need to add more liquid to
account for the volume that the stirring rod occupied.

Constantly stir when you're adding two liquids

together.

Stir smoothly and don't shake an oral liquid when it's

being prepared. This could cause foaming.

Add thicker (high-viscosity) liquids to less viscous

liquids.

Make sure that particle size of the active drug is

reduced to minimize the grittiness of the formulation.

Talk to your colleagues about your

compounding questions at

Calculations and Conversions

Correct calculations and preventing errors are extremely
important when compounding. A 42 year-old man was
hospitalized due to a life-threatening error caused by a
pharmacy during compounding. While compounding a littleused drug, the capsules were compounded with ten-times the
intended dosage.8
Conversions
You may remember learning the apothecary and avoirdupois

measurement systems in your training. Apothecary units like the "dram"

(1/8th of an ounce), the "minim" (1/480
(1/480th of an ounce), and avoirdupois units like the grain (about 1/438
of an ounce) were used.2
It should be noted that the Institute for Safe Medication Practices
advocates exclusive use of the metric system, and avoidance of these
units. Being so rarely used, these symbols can be mistaken for more
commonly used abbreviations.5
Most modern recipes and formulation records will follow the metric
system. If you encounter a recipe or formulation that uses another system,
consider converting it to metric, with another staff member doublechecking your calculations. This is a good idea from the perspective of
both convenience and safety.
Following are some conversions that you might find useful:
Weight
1 kilogram = 2.2 pounds (avoir)
1 pound = 454 grams
1 ounce (avoir) = 28.35 grams
1 gram = 15.432 grains
Liquid
1 fluid ounce = 29.57 milliliters
1 pint = 473 milliliters
1 gallon = 3785 milliliters
Calculations involved in compounding can range from simple to
complex. However, for the most basic compounded products, you're most
likely to encounter simple algebra and conversions.
Calculations
Following are some formulas that can come in handy for compounding.
Percentage conversions might be required for determining the percentage
concentration of ingredients in a compounded product that gives only the
weight of each ingredient. Formulas that can be used for percentage
conversions include the following:
Volume percent (v/v) = volume of solute
volume of solution
Weight percent (w/w) = weight of solute

weight of solution
Weight in volume percent (w/v) =
Here's an example:
Isotonic saline, or normal saline, is 0.9% sodium chloride. How many
grams of sodium are in 50 mL of normal saline?
0.9% = X g sodium chloride
50 mL of normal saline
X g sodium chloride = 50 * 0.9%
100%
X = 0.45 g of sodium chloride
Dilution is another calculation that might be required. Both liquids and
solids can be diluted. Following are formulas you can use for figuring out
dilutions:
quantity of solution 1 * concentration of solution 1 =
quantity of solution 2 * concentration of solution 2
You have probably used this equation many times. It's a simple
proportion, and is handy in many situations. Here's an example:
You need to prepare a pediatric dose that's very small (5 mg). The drug
product that you have available is very concentrated (62.5 mg/mL), so
that measuring a very small dose is not practical. You'd like to make a
dilution that's 5 mg/ml, and you need 20 mL. So you set up the following
equation:
5 mg/mL * 20 mL = 62.5 mg/mL *
X = 1.6 mL of the 62.5 mg/ mL product
Proportions can be used for many different pharmacy calculations,
including figuring the amount of drug in a salt form, and reconstituting
drugs using volumes other than those on the label.
Reducing and enlarging formulas
A recipe won't always be written for the amount of a compounded
product that is actually needed. Again a simple proportion can be used.
Here's an example:

A recipe for 50 mL of a medicated gel requires 1.2 gm of the active

ingredient. However, the prescription is written for 2 ounces (60 mL) of
gel. You can set the equation up as follows:
1.2 gm active ingredient = X
50 mL
60 mL * 1.2 gm = X gm active ingredient
50 mL
X = 1.44 gm active ingredient
To get more practice with pharmacy calculations, get one of
our PL CEs for technicians,
or Math and Measurements Part 2
Preventing Errors
USP Chapter 795, Pharmaceutical Compounding-Non-sterile
Preparations, defines the responsibilities of the compounder in ensuring
the quality of compounded products. These include (but are not limited
to) the following:1

The compounding environment is suitable for its intended

purpose.

There is assurance that processes are always carried out as

intended or specified and are under control.

Compounding conditions and procedures are adequate for

preventing errors.

Adequate procedures and records exist for investigating and

correcting failures or problems in compounding, testing, or in the
preparation itself.

Steps are also suggested to minimize error. There are 13 steps, and they
are listed here, verbatim, from USP Chapter 795:
1. Judge the suitability of the prescription to be compounded in
terms of its safety and intended use. Determine what legal
limitations, if any, are applicable.
2. Perform necessary calculations to establish the amounts of

ingredients needed.
3. Identify equipment needed.
4. Don the proper attire and wash hands.
5. Clean the compounding area and needed equipment.
6. Only one prescription should be compounded at one time in a
specified compounding area.
7. Assemble all necessary materials to compound the prescription.
8. Compound the preparation following the formulation record or
prescription, according to the art and science of pharmacy.
9. Assess weight variation, adequacy of mixing, clarity, odor, color,
consistency, and pH as appropriate.
10. Annotate the compounding log, and describe the appearance of
the formulation.
11. Label the prescription containers to include the following items:
a. the name of the preparation;
b. the internal identification number;
c. the beyond-use date;
d. the initials of the compounder who prepared the label;
e. any storage requirements;
f. any other statements required by law.
12. Sign and date the prescription affirming that all procedures were
carried out to ensure uniformity, identity, strength, quantity, and
purity.
13. Thoroughly and promptly clean all equipment, and store properly.
The Institute for Safe Medication Practices (ISMP) cites an instance of a
pharmacist discovering that his partner had been improperly
compounding a medication over a four-year period, as a result of

ambiguous instructions written by the original pharmacist who filled the

prescription. As a result, ISMP recommends institution of a process to
ensure that all compounding recipes undergo a documented approval
process before use. A double-check process should be used for all
calculations completed each time a compound is made. ISMP
recommends weekly review of a logbook of all compounds prepared, as
well as using each refill as an opportunity for a quality control check.
Test Your Knowledge
A prescriber calls to ask if you can make a
she wants to try it for vaginal administration for one of her patients, who
is a long-time patient at your pharmacy.
You check your resources and find a recipe for sildenafil topical cream.
Question #15
Your recipe
does
The recipe with the heading "sildenafil
topical
cream" contains the
not indicate the
following ingredients:7
percentage of
Sildenafil citrate tablets 1 g sildenafil in the
cream. You
Propylene glycol 10 g
the
Oil-in-water emulsion base qsdouble-check
100 g
recipe and find
it contains
The prescriber says that's exactlythat
what
she wants and that she'll send the

patient your way.

a. Sildenafil 1%
b. Sildenafil
The following prescription is presented:
10%
c. Sildenafil
0.1%
d. Sildenafil
1.5%
Question
A prescriber calls you with a special
request.#16
He needs to prescribe
spironolactone liquid for a 3 month-old
male,
You have the MK. MK was hospitalized
for several weeks following birth,
and wasbases
receiving spironolactone to
following
improve lung function. The doseavailable.
of spironolactone
Which for MK is 1
mg/kg/dose every eight hours, and
weighs
oneMK
would
you 5.5 kg. The hospital
pharmacy was preparing the spironolactone
when MK was an inpatient,
choose for this
but now the pediatrician is having
a hard time figuring out how to get it
recipe?
for MK as an outpatient. Can you
help?
a. White
petrolatum
The prescription reads as follows:

b. Aquaphor

c. Dermabase


d. Aquabase

You check through the available recipes in your pharmacy. You do not
have a recipe for spironolactone liquid.
Question
#17 is glad to share the
You call the hospital pharmacy and
the pharmacist
recipe for spironolactone liquid. IfYou
receive
a fax copy of the recipe, and
you could not
it's actually quite simple. The recipe
as follows:
find is
a recipe
for
spironolactone
Spironolactone 5 mg/mL liquid in the
references that are
available
Spironolactone 100 mg tabs
x 10 to you,
Sterile water 10 to15 mL which of the
following are
Cherry syrup, qs to 200 mL
potential resources
for acoating
recipe dissolves
for
Wet tabs in sterile water until
spironolactone
Crush tablets
Add cherry syrup to make liquid?
a total volume of 200 mL
a. The
Expiration: 2 months
manufacturer of
Auxiliary label: Refrigerate spironolactone,
the package
Source: Jew RK, Mullen RJ,or
Soo-Ho
W.
insert
for
the Society of Hospital
Formulations. Washington, DC: American
drug
Pharmacists, 2003.
b. The
pharmacy
at the
You check that you have the necessary
supplies,
and indeed you do.
hospital
where
However, you do not have any spironolactone 100 mg tablets. But you do
MK
was a
have plenty of spironolactone 50 mg
tablets.
patient
c. A drug
information
center
d. All of the
above
Wrapping It Up
Question #18
After you record
Although requests for compounded
this drugs
recipemight
for not be an everyday
occurrence, providing this service
can be a real convenience for patients
spironolactone,
who need it. Stay on top of compounding
you knowbasics,
that so that you can be ready
to help patients whose needs aren't
metpractice"
by commercially
available drug
"best
is

products.

to
a. make sure
there's a second
Here's a list of compounding resources:
check of the
recipe before it's
Recipes
used in your
pharmacy.
When looking for recipes for extemporaneous
dosage forms prepared
b. file the recipe
from commercially available products,
consider checking the product's
immediately.
package insert, or contacting the
manufacturer,
c. alter the a local pharmacy school,
7
or a drug information center. The recipe to include
texts, like Trissel's Stability of Compounded
only the Formulations
Science, and Technology of Pharmaceutical
Compounding
supplies and
CompoundingToday.com is a goodequipment
source forthat
recipes as well.
you have
Other Compounding Resources available.
d. determine
www.pcab.org
beyond-use
dating for this
o Pharmacy Compounding
Accreditation Board (PCAB)
patient's
prescription.
o A voluntary program to improve compounding activity

Question #19
What's the most
appropriate
o United States Pharmacopeial
volume of (USP) Convention
spironolactone
o USP establishes standards
fortocompounding
medications
suspension
be
prepared for this
www.pccarx.com
patient?

a. 40 mLCenters of America (PCCA)

o Professional Compounding

b. 100 mL
o Provides compounding education and training, as well
pharmaceutical ingredients,
equipment, devices, bases, and

c. 200 mL
formulations.

d. 240 mL
www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/
PharmacyCompounding/default.htm
Question #20
o FDA Pharmacy Compounding
How many
spironolactone 50
tablets areon FDA's activities that
o Website providesmg
information
needed
to prepare
pertain to pharmacy
compounding
the volume of
www.usp.org

spironolactone
suspension for this
patient?
o Website managed
by
International
Academy of
a. the
Four
tablets.
This calculation
Compounding Pharmacists
should be
CompoundingToday.com double-checked
before the
prescription
is website by the
o A very comprehensive
subscription
dispensed,
and
International Journal of Pharmaceutical Compounding
the strength of
the tablets
used
Recent Information from Pharmacist's
Letter
should
be
noted
Compounding
on the
Alcohol Products: How Docompounding
They Differ?
record.
b. TenExposure
tablets.
Compounding KI for Radiation
This calculation
should be
FDA Takes Action Against Compounded Bioidentical Hormones
double-checked
before the
Magic Mouthwash
prescription is
dispensed.
TriMix-gel for Erectile Dysfunction
c. Ten tablets.
This calculation
We also have a letter that you can give
to providers
should
be
you are glad to provide compounded
products
for their patients.
double-checked
before the
prescription is
dispensed, and
the strength of
tablets used
should be noted
on the
compounding
record.
d. Five tablets.
This calculation
should be
double-checked
before the
prescription is
dispensed, and
the strength of
the tablets used
should be noted

www.iacprx.org

on the
compounding
record.
References
1. USP Pharmacists' Pharmacopeia. Rockville, MD: The United States Pharmacopeial
Convention, 1995.
2. Young L, Ed. The Art, Science, and Technology of Pharmaceutical Compounding. 2nd
ed. Washington, DC: American Pharmaceutical Association, 2002.
3. Ansel HC. Introduction to Pharmaceutical Dosage Forms, 4th edition. Philadelphia,
PA: Lea and Febiger, 1985.
4. Anon. The UNC School of Pharmacy Compounding Lab. http://pharmlabs.unc.edu
(Accessed February 15, 2012).
5. Institute for Safe Medication Practices. Error-prone Abbreviation List. www.ismp.org
(Accessed February 15, 2012).
6. Anon. ISMP Ambulatory Care Action Agenda. Institute for Safe Medication Practices.
www.ismp.org (Accessed February 15, 2012).
7. Anon. Sildenafil 1% topical cream. Int J Pharm Compound 2001;5:379.
8. Schwam E. Severe accidental overdose of 4-aminopyridine due to a compounding
pharmacy error. J Emerg Med 2009;41:51-4.