1. COMPOUNDING
CHAPTER 8

2. 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

3. 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

4. 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

5. COMPOUNDING Compounding Manufacturing
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

6. 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.

7. 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

8. REGULATION OF COMPOUNDING
The USP-NF also publishes monographs of commonly compounded preparations
Stability information
Beyond-use dates

9. 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…

10. 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)

11. STABILITY AND BEYOND-USE-DATES
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”

12. 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

13. 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.

14. TYPES OF EQUIPMENT Measuring Mixing Molding Packaging
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

15. BALANCES Types Reasons to accurately weigh 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.

16. 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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17. Using a Class A Torsion Balance
Place on a level surface in a draft free area.
Level front-to-back and left-to-right.
Use clean weigh papers or boats with each new material.
Arrest the balance before adding or removing weight or material.
Use a spatula; do not pour from a bottle.
Clean balance after use.

18. USING AN ELECTRONIC BALANCE
Place on a level surface in a draft free area.
Level front-to-back and left-to-right.
Turn on the balance; if first use of the day, check internal weight calibration.
Use clean weigh papers or boats with each new material
Use a spatula: it may be necessary to remove the draft shield to introduce or remove material.
Clean balance after use.
Turn off balance at end of day.

19. VOLUMETRIC EQUIPMENT Non-volumetric Glassware Volumetric Glassware
Erlenmeyer flasks
beakers
prescription bottles
Volumetric Glassware
graduated cylinders
volumetric flasks
pipets
syringes
burets
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20. 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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21. LIQUID MEASURING DEVICES
Droppers
Graduated cylinders
Single volume pipets
Calibrated pipets
Syringes
Oral syringes

22. 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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23. 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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24. MEASURING LIQUIDS Calibrated Pipet Single Volume Pipets
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25. 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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26. 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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27. MIXING SOLIDS AND SEMISOLIDS
Mixing powders/geometric dilution
Spatulation
Ointment slabs
Levigation
Electronic mortar and pestle
Ointment mill

28. 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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29. OINTMENT SLAB
An ideal surface for mixing compounds because of its nonabsorbent surface.
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30. SPATULAS Spatulas Types
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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31. 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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32. LEVIGATION
Reduces particle size of a powder drug by triturating it with a solvent in which the drug is insoluble
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33. 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

34. 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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35. 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

36. 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

37. 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

38. 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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39. 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

40. 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

41. 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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42. SUPPOSITORIES Ways to compound suppositories compression molding
fusion molding
Suppository molds
metal (steel, aluminum)
plastic
rubber
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43. 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)
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44. PUNCH METHOD* *used when filling a small number of capsules
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45. 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

46. 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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47. 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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