Non Sterile Pharmaceutical Compounding

Chapter Topics

• Sterile and nonsterile compounding• Laws, regulations, and standards• Regulations of pharmacy personnel• Documentation of nonsterile compounding• Equipment for weighing, measuring, and compounding• Techniques for mixing compounded drugs• Compounding of specific formulations• The compounding process• Reference sources for the compounding pharmacy

Learning Objectives

• Define the term compounding, describe common situations in which compounding is required, and identify rationale and examples of nonsterile compounding.

• Discuss the impact of the Food and Drug Administration Modernization Act (FDAMA) of 1997 on the practice of a compounding pharmacy.

• Understand the distinction between a manufactured product and a compounded nonsterile preparation.

• Define the regulatory role of the state board of pharmacy.• Identify quality standards for nonsterile compounding

contained in USP Chapter <795>.

Learning Objectives (continued)

• Review and follow the components of good compounding practices in the pharmacy.

• Discuss reasons and process for accreditation of specialty compounding pharmacies.

• Understand the minimum training and attire requirements for pharmacy technicians in a compounding pharmacy.

• Distinguish the components and purpose of a master control record from a compounding log.

• Define percentage of error and understand how it relates to accuracy in the compounding pharmacy.

• Identify and describe the function of the equipment used for the weighing, measuring, and compounding of pharmaceuticals.

Learning Objectives (continued)

• Explain the proper techniques for weighing pharmaceutical ingredients, measuring liquid volumes, and compounding nonsterile preparations.

• Define the various terms used for comminution and blending.• Examine the techniques by which solutions, suspensions, ointments,

creams, powders, suppositories, and capsules are prepared.• Understand and calculate common mathematical problems that

occur in a compounding pharmacy.• Identify the steps necessary in the compounding process.• Compare the reimbursement procedures of a compounding

pharmacy and a retail pharmacy.• Identify references with a focus on compounding.

Sterile and Nonsterile Compounding

• Compounding– The process of preparing a medication for an individual

patient from bulk ingredients according to a prescription by a licensed prescriber

Situation requiring compounding ExampleDose for pediatric patient smaller than commercially available dose

Preparing 10 mg capsules from 30 mg tablets

Patient cannot swallow solid dosage form Preparing a suspension from tablets

Dose for veterinary application that is not commercially available

Preparing a thyroid medication for a cat

Medication has unpleasant taste Preparing a flavor-masking syrup for a pediatric patient

Oral medication causes adverse effect Preparing a gel for a patient who has had ulcers from oral medication

Laws, Regulations, and Standards

• Food and Drug Administration Modernization Act of 1997– Allows pharmacists to compound

nonsterile (and/or sterile medications) for an individual patient if these medications meet established USP standards

– Compounding pharmacies overseen by state board of pharmacy

Laws, Regulations, and Standards (continued)

• Food and Drug Administration Modernization Act of 1997– Compounding a commercially available product is

prohibited– Compounding pharmacies not required to follow

current good manufacturing practices, adhere to product labeling, or submit drug approval applications

– If community pharmacy selling products to healthcare professionals or out-of-state pharmacy, must apply for manufacturing license

Laws, Regulations, and Standards (continued)

• USP Chapter <795>– USP standards developed to enhance patient

safety from nonsterile compounded products

– Manufactured products• Prepared off-site by large-scale drug manufacturer

– Compounded preparation• A patient-specific medication prepared on-site

Laws, Regulations, and Standards (continued)

• USP Chapter <795>– Sources for bulk ingredients• Decision based on cost, quality, purity, reputation of

manufacturer• Pharmaceutical Compounding Centers of America

(PCCA) primary source for many large-volume compounding pharmacies• More than one source recommended in case of

shortage, back order, or product recall

Laws, Regulations, and Standards (continued)

• USP Chapter <795>– Beyond-use dating• The documentation of the

date after which a compounded preparation expires and should no longer be used• Initiated when product

compounded not when dispensed

Pharmacy technicians should understand the distinction between a beyond-use date and an expiration date: A beyond-use date is a term that applies to compounded preparations, whereas an expiration date is a term that applies to manufactured products.

In the Know: True or False

• A pediatric dose that is smaller than what is commercially available would require compounding.

true • It is okay to compound a commercially available product.

false • USP Chapter <797> provides standards for compounding

nonsterile products.false

• Beyond-use dating is the date after which a compounded product can no longer be used.

true

Laws, Regulations, and Standards (continued)

• USP Chapter <795>– Estimates for beyond-use date• Refrigerated aqueous solution or suspension: 14 to 30

days• Solids such as tablets and capsules: 6 months or less

– Beyond-use date for prescription with two or more active or inactive ingredients• Take 25% of the remaining expiration date or six

months, whichever is earlier

Laws, Regulations, and Standards (continued)

Laws, Regulations, and Standards (continued)

• Accreditation– Provides competitive edge in the

marketplace– Voluntary accreditation through the

Pharmacy Compounding Accreditation Board (PCAB)

– Pharmacy must agree to meet all standards for sterile and nonsterile compounding

– Includes monthly or quarterly spot check• Random product sent to outside lab for

analysis• Product must be +/-2% of potency • Any corrective action must be documented

and dated by pharmacist

Regulations for Pharmacy Personnel

• Technician training– Successfully passing a broad

national certification exam– Mini-certifications and laboratory

training in nonsterile and sterile compounding

• Nonsterile compounding attire– Clean, protective clothing, hairnet,

long lab coat, disposable gloves– If hazardous chemicals to be used,

eye goggles, mask, double gowning

Documentation of Nonsterile Compounding

Master Control Record Compounding Log

Purpose A recipe for a compounded preparation

A printout from the master control log used to prepare a compounded prescription

Components Drug nameDrug strengthDrug dosage formIngredients and quantitiesSequencing and mixing instructionsBeyond-use datingStorage and labeling information

Patient nameDate of compoundingRx numberMaster Control Record numberNames of ingredients and their expiration datesAmount neededQuantity madeManufacturerWholesaler sourceNDC numberAssigned lot numberInitials of pharmacist and compounding technician

In the Know: True or False • USP good compounding practices has standards regarding

education of personnel.true

• Accreditation by the Pharmacy Compounding Accreditation Board is involuntary.

false• A face mask must be worn when compounding nonsterile

products.false

• A product’s assigned lot number should be included on the compounding log.

true

Measuring and Compounding Equipment

• Equipment for weighing– Two-pan balances

• Class III prescription balance– Capacity of 15 to 120 grams– Should be used to measure no less

than 120 mg to maintain acceptable error of less than 5%

– Sufficient for infrequent compounding in community pharmacy

• Counterbalance– Used for weighing larger amounts of

materials (up to 5 kg)– Used for measuring bulk products

Measuring and Compounding

Equipment (continued)• Equipment for weighing– Pharmaceutical weights

• Used on a two-pan balance to offset the ingredient weight

• Sets contain metric and apothecary weights

– Weighing paper• Special paper placed on a weighing

balance pan to avoid contact between pharmaceutical ingredients and the balance tray

• Glassine paper used which is coated with paraffin wax

Measuring and Compounding Equipment (continued)

• Equipment for weighing– Class III prescription balance

Measuring and Compounding Equipment (continued)

• Equipment for weighing– Digital electronic analytical balance• Uses a single pan, does not need pharmacy weights

Measuring and Compounding Equipment (continued)

• Percentage of error– The acceptable range of variation above and below the

target measurement– Based on the least weighable quantity of an ingredient– If sample is too small, margin of error may be unacceptable– Compounded nonsterile preparations must have an error

range less than 5%

Percentage of error = amount of error X 100 quantity desired

Measuring and Compounding Equipment (continued)

• Measuring devices for liquids– Graduated cylinders

• A glass or polypropylene flask used for measuring liquids

• Conical and cylindrical shapes, range from 5 mL to more than 1000 mL, calibrated in both metric and apothecary units

When measuring liquids with a graduated cylinder, pipette, oral syringe, or dropper, always use the smallest size that can contain the volume to be measured. Doing so minimizes your percentage of error in measurement.

Measurement and Compounding Equipment (continued)

• Measuring devices for liquids

Measuring and Compounding Equipment (continued)

• Measuring devices for liquids

Measuring and Compounding Equipment (continued)

• Measuring devices for liquids– Pipette

• A long, thin, calibrated hollow tube used for measuring small volumes of liquids

• Pipette filler or rubber bulb works like a suction device

– Oral syringe• Used to measure small or large

quantities• More accurate than graduated

cylinders when measuring thick, viscous liquids

Measuring and Compounding Equipment (continued)

• Supplies for mixing and molding ingredients– Mortar and pestle

• Used for mixing and grinding pharmaceutical ingredients

– Beakers and flasks• Glassware which store, contain, and mix liquids

– Ointment mill• Mixes and greatly reduces the particle size of

powders used to make ointments or creams

– Ointment slab• Plate of ground glass used for mixing topical

compounds

In the Know: Fill in the Blank

• Measurements of a liquid solution should be taken at the bottom of the _________.

meniscus• An _____ ________ is more accurate than a

graduated cylinder when measuring viscous liquids.oral syringe

• A _______ and ______ is used for mixing and grinding pharmaceutical ingredients.

mortar; pestle

Measuring and Compounding Equipment (continued)

• Supplies for mixing and molding ingredients– Spatula

• Used for transferring solid pharmaceutical ingredients to and from weighing pans, preparing ointments and creams, transferring the compounded product into its final container

– Molds and presses• Molds used for making

suppositories or troches• Presses used to make an

implantable urethral pellet of medication

Techniques for Mixing Compounded Drugs

• Comminution and blending

– Comminution• The act of reducing a substance to fine

particles

– Blending • The act of combining two substances

Techniques for Mixing Compounded Drugs (continued)

• Communition and blending– Techniques include• Trituration• Levigation• Pulverization• Spatulation• Sifting• Tumbling• Geometric dilution

Techniques for Mixing Compounded Drugs (continued)

Process Description of process Equipment used

Trituration Rubbing, grinding, or pulverizing a substance to create fine particles

Mortar and pestle

Levigation Reducing the particle size of a solid when preparing an ointment by adding a levigating agent

Glass mortar or ointment slab

Pulverization Reducing the particle size by adding a solvent Mortar and pestle

Spatulation Combining and mixing substances with a spatula Spatula, ointment slab

Sifting Blending or combining powders using a sieve Mesh sieve, glassine paper

Tumbling Combining powders by placing them in a bag or container and shaking it

Bag, container

Geometric dilution method

Used for combining several ingredients—successively larger amounts added, equal to the amount in the mortar

Mortar and pestle

Compounding of Specific Formulations

• Powders– Powders are combined and mixed by trituration,

spatulation, sifting, and tumbling.

• Tablets and troches– Compression tablets are formed by weighing powders,

placing them in a die, then compressing the ingredients.– Rapid-dissolving tablets are formed by mixing powders,

placing them in a mold, and then baking them in a convection oven.

Compounding of Specific Formulations (continued)

• Capsules– Capsule filled by “punching” it into a cake of the powder or by using a capsule

machineProblem

Nystatin powder has an activity of 100,000 units/g. How many milligrams of nystatin would you use in each capsule if the final preparation is supposed to be 1,500,000 units per capsule?

Convert 100,000 units/g to units/mg:100,000 units/g X 1 g/1000 mg = 100 units/mg

Determine the amount of milligrams needed in each capsule:X mg = 1 mg

1,500,000 units 100 units

x mg = 15,000 mg

Compounding of Specific Formulations (continued)

• Solutions– Prepared by dissolving the solute in the

solvent or diluting existing solutions

Compounding of Specific Formulations (continued)

• Suspensions– Tablets are triturated into a

powder, a suspending agent (acacia, carboxymethylcellulose) is added, and then the mixture is dispersed in a liquid vehicle.

Regardless of their apparent stability, all suspensions should be dispensed with an auxiliary label stating, “Shake Well.”

Compounding of Specific Formulations (continued)

• Ointments, creams, and lotions– When combining ointments or creams, mix them

with a mortar and pestle or an ointment slab.– If dry ingredients are used, triturate to a fine

powder then add the powder to the ointment base in small amounts.

– If mixing three or more ingredients to the base, add them using the geometric dilution method.

Compounding of Specific Formulations (continued)

• Suppositories– Prepared by melting the

base material, adding the active ingredients, pouring the resultant liquid into a mold, and then solidifying at room temperature

In the Know: Short Answer

• What is the term for the process of pulverizing a substance to create fine particles?

trituration• What is the term for the process of combining

powders by placing them in a bag?tumbling

• Suppositories should be solidified at _____ temperature.

room

The Compounding Process

Pharmacist judges the suitability of the

prescription.

Pharmacist retrieves and reviews the master control

record.

Pharmacist prints out a compounding

record for the technician.

Pharmacist performs calculations and

identifies necessary equipment.

A medication container label is

created.

Pharmacy technician uses appropriate

protective clothing and hand-washing

technique.

The Compounding ProcessSteps 1 through 6

The Compounding Process (continued)

Technician gathers all ingredients, prepares and

calibrates equipment.

Technician weighs and adds

ingredients, initials steps, documents it

on compounding record.

Technician stores product in a suitable

container.

Technician affixes medication

container label.

Pharmacist reviews the compounding

record and medication

container label, checks the product.

Pharmacist signs and dates the

compounding log, files it in records, and

puts product in storage bin for patient pickup.

The Compounding ProcessSteps 7 through 12

The Compounding Process (continued)

Technician cleans equipment, reshelves ingredients, and

properly labels and stores excess product.

Pharmacist counsels patient at time of pickup.

The Compounding ProcessSteps 13 and 14

The Compounding Process (continued)• Reimbursement– The majority of the cost of a compounded product is

based on the work time of pharmacy personnel, not the ingredients.

– Insurance does not immediately cover the cost of a compounded prescription.

– If a patient pays out-of-pocket, the compounding pharmacy provides the patient with a Universal Claim Form (UCF), which is then submitted to insurance.

– UCF includes NDC numbers, cost of each ingredient, time to prepare.

Reference Sources for the Compounding Pharmacy

• Remington: The Science and Practice of Pharmacy– Standard reference source

• Professional Compounding Centers of America (PCCA)– Membership entitles the compounding pharmacy to the master

formulas– Holds educational and certification seminars

• Pharmacists’ Pharmacopeia – Published by United States Pharmacopeia (USP)– Contains monographs for more than 120 compounded

preparations

Reference Sources for the Compounding Pharmacy (continued)• Secundum Artem: Current & Practical

Compounding Information for the Pharmacist

• International Academy of Compounding Pharmacists (IACP)– Political action group which promotes personalized

medication solutions for patients– Also keeps compounding pharmacy personnel

aware of legislative challenges that have an impact on their profession

Chapter Summary• Nonsterile compounding is used to prepare medications not available

commercially.• Pharmacies must follow good compounding practices as outlined in

USP Chapter <795>.• Quality of bulk ingredients is important in compounding a high-

quality product.• Beyond-use dating must meet USP guidelines.• Many compounding pharmacies seek national accreditation for

marketing and reimbursement.• Pharmacy technicians often need additional training and certification

to practice in a compounding pharmacy.• Minimum proper attire includes a long lab coat, hairnet, and

disposable gloves.

Chapter Summary (continued)

• The compounding log documents the patient-specific prescription.

• There are a variety of instruments used for nonsterile compounding.

• Proper technique and the use of correct measuring devices are crucial when weighing and measuring ingredients.

• Geometric dilution is used when mixing potent or toxic ingredients.

• Compounding is used to prepare many dosage forms.• There are several steps in the compounding process.• The pharmacist is legally responsible for the final check and for

counseling the patient.