COMPOUNDING CHAPTER 8. CHAPTER OUTLINE Compounding Regulations Stability & Beyond-Use Dates Compounding considerations Equipment Using a Balance Volumetric.

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.


• 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


• The USP-NF also publishes monographs of commonly compounded preparations

Stability information Beyond-use dates


• 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

copied, re-used, reproduced, or re-transmitted without express written permission from the publisher.

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

Image copyright Perspective Press and Morton Publishing Company. May not be copied, re-used, reproduced, or re-transmitted without express written permission

from the publisher.

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.Image copyright Perspective Press and Morton Publishing Company. May not be


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.


from the publisher.

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.


from the publisher.

MEASURING LIQUIDSCalibrated Pipet

Single Volume Pipets

Images copyright Perspective Press and Morton Publishing Company. May not be copied, re-used, reproduced, or re-transmitted without express written permission from

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.

Oral syringes can be used with an Adapt-a-Cap®.Image copyright Perspective Press and Morton Publishing Company. May not be copied, re-used, reproduced, or re-transmitted without

express written permission from the publisher.

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

Image copyright Perspective Press and Morton Publishing Company. May not be copied, re-used, reproduced, or re-transmitted without express written permission from the publisher.

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.

Images copyright Perspective Press and Morton Publishing Company. May not be copied, re-used, reproduced, or re-transmitted without express written permission from the publisher.

OINTMENT SLAB

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


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

Image copyright Perspective Press and Morton Publishing Company. May not be copied, re-used, reproduced, or re-transmitted without express written permission from the

publisher.

SPATULATION

• Mixing powders using a spatula

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


LEVIGATION

•Reduces particle size of a powder drug by triturating it with a solvent in which the drug is insoluble


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.


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


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

Image copyright Perspective Press and Morton Publishing Company. May not be copied, re-used, reproduced, or re-transmitted without express written permission from the

publisher.

SUPPOSITORIES

• Ways to compound suppositories compression molding fusion molding

• Suppository molds metal (steel, aluminum) plastic rubber


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


PUNCH METHOD*

*used when filling a small number of capsules


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


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


COMPOUNDING CHAPTER 8. CHAPTER OUTLINE Compounding Regulations Stability & Beyond-Use Dates Compounding considerations Equipment Using a Balance Volumetric.

Documents

uspnf standards

uspnf chapters

form patients

enforcement of usp

hospice patients

drug productaccording

pediatric patients

regulation of compoundingusp