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 500mgImage copyright Perspective Press and Morton Publishing Company. May not be
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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
material5. 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.
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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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from the publisher.
MEASURING LIQUIDSCalibrated Pipet
Single Volume Pipets
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the publisher.
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.
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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®Images copyright Perspective Press and Morton Publishing Company. May not be
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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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