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COMPOUNDING



CHAPTER 8


CHAPTER OUTLINE


Compounding


Regulations


Stability & Beyond
-
Use Dates


Compounding considerations


Equipment


Using a Balance


Volumetric Equipment


Measuring Liquids


Mixing Solids and Semisolids


Compounding Select Dosage
Forms


Aqueous Solutions


Syrups


Nonaqueous

Solutions


Suspensions


Flavoring


Sweeteners


Coloring


Emulsions & Emulsifiers


Ointments


Suppositories


Capsules


Tablets


Review



COMPOUNDING


Chapter Outline


Compounding


Regulations


Stability and Beyond
-
Use Dates


Compounding Considerations


Equipment


Using a Balance


Volumetric Equipment


Measuring Liquids


Mixing Solids and Semisolids


Compounding Select Dosage Forms

WHY COMPOUND?



Pediatric patients requiring diluted adult strengths of drugs



Patients needing an oral solution or suspension of a product that is
only available in another form



Patients with sensitivity to dyes, preservatives, or flavoring agents
found in commercial formulations



Dermatological formulations with fortified (strengthened) or diluted
concentrations of commercially available products



Specialized dosages for therapeutic drug monitoring



Care for hospice patients in pain management



Compounding for animals

COMPOUNDING


Compounding


On
-
demand preparation of a drug product


According to a physician’s prescription


Meets the unique needs of an individual
patient



Manufacturing


Production or processing of a drug or device


Packaging or labeling for re
-
sale to
pharmacies or practitioners


REGULATION OF COMPOUNDING


Compounding is regulated by the individual
states’ boards of pharmacy.



USP
-
NF has federal authority to set standards
pertaining to pharmacy compounding and
manufacturing.



Some states accept the USP
-
NF standards as
their standards. Some states do not.

REGULATION OF COMPOUNDING


USP
-
NF is a resource published yearly.



USP
-
NF Chapters are assigned numbers


Chapters numbered below 1,000 are legally
enforceable by the FDA.


Chapters numbered above 1,000 are
informational chapters.



Enforcement of USP
-
NF chapters by the FDA
-

not always clear
-
cut (jurisdiction resides with
the states)


Case
-
by
-
case basis

REGULATION OF COMPOUNDING


The USP
-
NF also publishes monographs

of commonly compounded preparations



Stability information


Beyond
-
use dates


REGULATION OF COMPOUNDING


USP
-
NF standards cover


Personnel


Facilities and Equipment


Ingredient Standards


Quality Assurance and Quality Control


Packaging and Storage


Documentation and Record Keeping


Many more…

DOCUMENTATION AND RECORD KEEPING


Formulation record


what should happen when the formula is
compounded


Compounding Record


what actually happened when the formulation was
compounded


Standard Operating Procedures


equipment maintenance and calibration, handling and
disposal of supplies, etc


Ingredients Record


certificates of purity from commercial vendors


Material Safety Data Sheets (MSDS)

STABILITY AND BEYOND
-
USE
-
DATES


Stability


The extent to which a dosage form retains the same
properties and characteristics it possessed at the time
it was made



Expiration date


The date until which the manufacturer can guarantee
the safety and full potency of a drug



determined after extensive study of the product’s stability




Beyond
-
use dates


Used for compounded preparations only and are
generally in the order of “days” or “months”

USP
-
NF RECOMMENDED BEYOND
-
USE
DATES*


Topical, dermal, mucosal liquid or semisolid
formulations containing water



not later than 30 days



Oral formulations containing water



not later than 14 days stored at a controlled cold
temperature



Nonaqueous formulations



the earliest expiration date of any active principle
ingredient (API) or 6 months, whichever is earlier



*
default dates if no other information is available

CONSIDERATIONS IN COMPOUNDING


Whether to compound


Is there a commercial product?


Before beginning


Are there appropriate personnel and
equipment?


Prepare a formulation record.


During compounding


Compound according to formulation record.


Complete a compounding record.


After compounding


Recheck all work.


Perform required equipment maintenance.



TYPES OF EQUIPMENT


Measuring


balance, weights, weigh
boats, volumetric
glassware (graduates,
pipets, flasks, syringes)



Mixing


beakers, Erlenmeyer
flasks, spatulas, funnels,
sieves, mortar and
pestle



Molding


hot plates, suppository
molds, capsule shells,
ointment slabs, tablet
molds



Packaging


prescription bottles,
capsule vials,
suppository boxes,
ointment jars


BALANCES


Types


Class A torsion balance


Electronic balance



Reasons to accurately weigh


One of the most essential parts of the compounding process


The product cannot be “checked” for content once dispensed to
the patient.


The quantities weighed are often very small, and a error could
mean an incorrect dosing of the patient.



CLASS A TORSION BALANCE


A two pan balance that uses both internal
and external weights


Weights go on the right pan


Weighted material on the left pan


Sensitivity: 6 mg or less


Capacity:

60 g or 120g



Weights


brass weights: 1 g to 50 g


fractional weights: 10mg to 500mg


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Using a Class A Torsion Balance

1.
Place on a level surface in a draft free area.


2.
Level front
-
to
-
back and left
-
to
-
right.


3.
Use clean weigh papers or boats with each
new material.


4.
Arrest the balance before adding or
removing weight or material.


5.
Use a spatula; do not pour from a bottle.


6.
Clean balance after use.


USING AN ELECTRONIC BALANCE

1.
Place on a level surface in a draft free area.

2.
Level front
-
to
-
back and left
-
to
-
right.

3.
Turn on the balance; if first use of the day, check
internal weight calibration.

4.
Use clean weigh papers or boats with each new
material

5.
Use a spatula: it may be necessary to remove the
draft shield to introduce or remove material.

6.
Clean balance after use.

7.
Turn off balance at end of day.

VOLUMETRIC EQUIPMENT


Volumetric Glassware



graduated cylinders


volumetric flasks


pipets


syringes


burets



Non
-
volumetric Glassware



Erlenmeyer flasks


beakers


prescription bottles

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MEASURING LIQUIDS


Selecting a liquid measuring device



Choose the smallest one capable of containing
the volume to be measured.



Avoid measurements of volumes that are
below 20 percent of the capacity of the device.



Example: a 100 ml graduated cylinder cannot accurately
measure volumes below 20 ml.



When measuring small volumes, use a syringe
or pipet.



Liquids have a
meniscus.

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LIQUID MEASURING DEVICES


Droppers


Graduated cylinders


Single volume pipets


Calibrated pipets


Syringes


Oral syringes

MEASURING LIQUIDS


Graduated cylinders


Cylindrical graduates are more accurate than
conical graduates.


Pour liquids into the center of the graduate.


Allow 15 seconds for aqueous and
hydroalcoholic liquids to drain from graduate.


Allow 60 seconds for syrups, glycerin, other
viscous liquids.


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MEASURING LIQUIDS


Droppers


Used to deliver small doses of liquid medication



Medicine dropper must first be calibrated


The drop size will vary from dropper

to dropper.


Personal factors will contribute to

dropper inaccuracy.

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MEASURING LIQUIDS

Calibrated Pipet

Single Volume Pipets

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MEASURING LIQUIDS


Syringes



Hypodermic or oral



Range from 0.5 ml to 60 ml



Always choose smallest size capable of containing
the volume to be measured.



Oral syringes can be used with an
Adapt
-
a
-
Cap
®
.


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MIXING SOLIDS AND SEMISOLIDS


Mortar and Pestle


Glass


mixing liquids and semisolids


Wedgwood


Porcelain



Trituration


The process of grinding powders to reduce

the particle size.

for triturating crystals and large particles

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MIXING SOLIDS AND SEMISOLIDS


Mixing powders/geometric dilution


Spatulation


Ointment slabs


Levigation


Electronic mortar and pestle


Ointment mill

MIXING POWDERS


GEOMETRIC
DILUTION

When mixing powders of unequal size, the smaller amount powder
is triturated with an equal amount of the larger amount powder.
That mixture is then mixed with an equal amount of the larger
amount powder. The process is repeated until the mixture is
completed.

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OINTMENT SLAB



An ideal surface for mixing compounds
because of its nonabsorbent surface.






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SPATULAS


Spatulas


used to transfer solid ingredients, prepare ointments
and creams, or loosening material from the surfaces
of a mortar and pestle



Types


stainless steel


hard rubber


plastic






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SPATULATION


Mixing powders using a
spatula



Can be done in a mortar, on
an ointment slab, or in a
plastic bag.

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LEVIGATION


Reduces particle size of a powder drug by

triturating it with a solvent in which the drug is
insoluble

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MIXING LARGE QUANTITIES


Electronic mortar and pestle


blade assembly inside a plastic mixing jar


length of time and speed of mixing can be
varied



Ointment mill


achieves very uniform particle size in
formulations


gives smoothness and elegance

SOLUTIONS


Clear (but not necessarily colorless) liquids

in which the drug is completely dissolved


The solubility of the drug must be known
before attempting to dissolve it in a
solution.


Some solids need to be triturated before
mixing into a solution.

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SOLUTIONS


Syrups


concentrated sucrose solution in
water



Nonaqueous solutions






Dissolve alcohol soluble ingredients in
alcohol, and water soluble ingredients in
water.



Add water solution to the alcohol solution.

Elixir

Glycerates

Tincture

Collodions

Spirit

Liniment

Fluid extract

Oleaginous solutions

SUSPENSIONS


A two phase system consisting of a finely
divided solid dispersed in a liquid



Flocculating agent


electrolytes used in the preparation of
suspensions to form particles that can be easily
redispersed



Thickening agent


ingredient used in the preparation of
suspensions to increase the viscosity of the liquid

ADDITIVES


Flavoring


The human tongue can distinguish salty, bitter,
sour, and sweet tastes.



Sweeteners


Colorless, odorless, solubility in water at the
concentrations needed for sweetening,
pleasant tasting with no “after
-
taste,” and
stable over a wide pH range



Coloring


Not required in every formulation


Contraindicated in all sterile solutions


Dark colors may be rejected because they are

often associated with poisons


EMULSIONS


Unstable system consisting of an oil and
water


One is dispersed in the form of small
droplets throughout the other.


Oil
-
in
-
water (o/w) emulsion


Water
-
in
-
oil (w/o) emulsion



Emulsifier


tragacanth, sodium lauryl sulfate, sodium
dioctyl sulfosuccinate, and polymers
known

as the Spans
®

and Tweens
®


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EMULSIONS


Methods of preparation


requires energy input



Dry Gum method


primary emulsion


4:2:1


gum + oil then water



Wet Gum method


mucilage


4:2:1


gum + water then oil



Beaker method


water soluble and oil soluble ingredients heated

in different beakers


add internal phase to external phase


OINTMENTS


Used for many different purposes


protectants


antiseptics


emollients


antipruritics



Methods to compound ointments


incorporate drug into ointment base


create the ointment base as part of compounding

SUPPOSITORIES


Oleaginous



primarily synthetic triglycerides


e.g., FattiBase
®
, Witepsol
®



Water soluble


glycerinated gelatin


dissolve slowly to provide prolonged release of active
ingredients


polyethylene glycols (PEGs)


200, 400, or 600 molecular weight are liquids


over 1,000 molecular weight are solids



Hydrophilic


mixtures of oleaginous and water soluble bases

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SUPPOSITORIES


Ways to compound suppositories


compression molding


fusion molding



Suppository molds


metal (steel, aluminum)


plastic


rubber


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CAPULES


Hard gelatin capsules consist of a body and a cap which fits
firmly over the body of the capsule.



8 sizes available for human use


Sizes


Volume (ml)

000


1.37


00


0.95


0


0.68


1


0.50


2


0.37


3


0.30


4


0.20


5


0.13

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PUNCH METHOD*


*
used when filling a small number of capsules

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CAPSULES


ADDITIONAL

COMPOUNDING TIPS


To avoid finger prints on the capsules, use a cap
as a holder, or use finger cots.



Liquids that do not dissolve gelatin can be
dispensed in capsules.


fixed oils



Tablets and smaller capsules can be placed
inside of a capsule.


reduces the number of single dosage forms

MOLDED TABLETS


Tablet base is a combination of lactose,
dextrose, sucrose, or mannitol


Ingredients in base are slightly dissolved with a
wetting solution (alcohol: water)


Pressed into a tablet triturate mold


must be calibrated

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TABLETS


OTHER COMPOUNDED TABLETS


Single punch tablet machine


chewable, effervescent, compressed tablets


Rapid dissolve tablets (RDT)


disintegrate or dissolve within minutes on
tongue


ingredients are very water soluble


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