Chapter 8 Created by Jennifer Majeske, Mineral Area College

Created by Jennifer Majeske, Mineral Area College

Non-sterile Pharmaceutical

CompoundingChapter 8


Define the term compounding, describe common situations in which compounding is required, and identify rationale and examples of non-sterile 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 non-sterile preparation.

Learning objectives


Define the regulatory role of the state board of pharmacy.

Identify quality standards for nonsterile compounding contained in USP Chapter <795>, including product selection and beyond-use or expiration dating.

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

Discuss reasons and process for accreditation of specialty compounded pharmacies.

Learning objectives


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 the term percentage of error and understand how the concept relates to accuracy in the compounding pharmacy.

Learning objectives


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

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

Define the various terms used for comminution and blending of pharmaceutical ingredients.

Learning objectives


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 that are necessary in the compounding process.

Compare reimbursement procedures of a compounding pharmacy and a retail pharmacy.

Identify references with a specialty focus on compounding.

Learning Objectives


Until the mid-nineteenth century, pharmacists routinely prepared (compounded) a majority of all prescriptions.

With large-scale manufacturing the need for compounding has lessened, some trends however indicate the practice is increasing.

Approximately 30-40 million prescriptions are compounded in the U.S. each year.

Extemporaneous compounding – compounding of nonsterile preparations or products that are not commercially available.

The need for compounding


Compounding – the process in which a pharmacist uses bulk ingredients to prepare a prescribed medication that treats a specific patient’s medical condition.

Sterile compounding – the process of using aseptic technique to prepare sterile solutions, or solutions that are free of microorganisms, for parenteral products or ophthalmic preparations.

Most sterile compounding is performed in the “clean room environment.”

Sterile and Non-sterile Compounding


Sterile compounding must be performed under strict controlled environmental conditions to minimize the risk of contamination of the compounded sterile preparations (CSPs).

CSPs are administered parenterally; prepared under strict federal and state regulations.

Most CSPs do not contain a preservative; these products have a brief beyond-use date of 24 – 72 hours due to sterility rather than stability concerns.

Sterile and Non-sterile Compounding


Non-sterile compounding – used in the preparation of commercially unavailable drug formulations from bulk ingredients in the community pharmacy.

Individualized prescriptions for patients. Unique medication requirements for animals;

catering to an animal’s species and size. What are some of the possible scenarios for

non-sterile compounding? What is the role of the technician in non-sterile

compounding?

Non-Sterile Compounding


For sterile and non-sterile compounding, federal and state laws and regulations along with United States Pharmacopeia (USP) standards and guidelines must be followed.

Professional organizations:◦ International Academy of Compounding Pharmacists

(IACP), American Pharmacists Association (APhA), American Society of Health-System Pharmacists (ASHP), National Community Pharmacists Association (NCPA)

Compounding pharmacies are allowed to advertise their services, but not the compounding of specific preparations.

Laws, Regulations, and Standards


Before 1997, there were no specific federal or state laws governing the practices of pharmacy compounding.

Pharmacists are allowed to, under the Food and Drug Administration Modernization Act of 1997, compound non-sterile and/or sterile medications for a patient if these medications meet USP standards.

Public health concerns are minor when mass production is not involved.

Compounded products are typically used for a small group of patients with specific medical needs.

Food and Drug Administration Modernization Act of 1997


Compounding pharmacies must be licensed by both state and federal governments.

Anticipatory compounding – pharmacies are allowed to prepare an excess product, as long as quantities are reasonable.

Pharmacies that compound and sell directly to other pharmacies or healthcare providers must apply for a manufacturing license.

The need for additional regulations was obvious in 2012 with an outbreak of fungal meningitis from epidural injections of a contaminated corticosteroid.◦ http://www.cdc.gov/hai/outbreaks/meningitis.html

Compounding Regulations

http://www.cdc.gov/hai/outbreaks/meningitis.html

http://www.cdc.gov/hai/outbreaks/meningitis.html


USP has developed standards to enhance patient safety and protect pharmacists from litigation.

USP Chapter <795> outlines protocol for non-sterile compounding; USP Chapter <797> outlines regulations for sterile compounding.

Manufactured products – produced by pharmaceutical manufacturers (Eli Lilly and Merck).

Compounded preparations – produced by pharmacies.

Good compounding practices (GCPs) – Table 8.1; all compounded products should be prepared using GCPs.

USP Chapter <797>


Quality controls consists of the use of high-grade pharmaceutical ingredients along with training of personnel, the preparations stability and consistency, safeguarding against calculation errors and documentation.

General Facility Requirements: ◦ Adequate storage and space◦ Appropriately maintained equipment◦ High cleanliness◦ Free of dust◦ Must have an eyewash station◦ Physically separate from the dispensing pharmacy

Non-sterile Compounding Environment


Quality of ingredients; only USP or National Formulary (NF) pharmaceutical-grade.

Sources for Bulk Ingredients: The source for ingredients depends on cost, quality, and purity of product.◦ Pharmaceutical Compounding Centers of America

(PCCA) is a primary source of products Pharmacists should have more than one

source of quality ingredients. Table 8.2 Bulk Product Contacts

Product Inventory


Storage of Bulk Ingredients: Ingredients are commonly ordered two to three times a week depending on volume and inventory.

Material Safety Data Sheet (MSDS) or Safety Data Sheet (SDS) – contains important information on hazards and flammability of chemicals and procedures for treatment of accidental ingestion or exposure.

Bulk ingredients are typically stored in tight, light resistant containers at room temp.

The technician should check expiration dates, the source of the ingredients, and the NDC number.

Product Inventory


Controlled Substances Inventory: Procedures and recording keeping for Schedule II compounds are detailed and extensive.

Controlled substance inventory must be in locked storage accessible only to the pharmacist.

Beyond-Use Dating – the expiration date of compounded preparations based on stability and temperature storage conditions.

Stability – the extent to which a product retains the same properties and characteristics that is possessed at the time of preparation.

Product Inventory


Beyond-use dating is initiated at the time of compounding.

Compounds should be prepared as close to the time of patient dispensing as possible.

USP Chapter <795> provides estimates for beyond-use dating.◦ Refrigerated aqueous solution or suspension has a

beyond-use dating of 14-30 days.◦ Solids, like tablets and capsules and non-aqueous

solutions have a beyond-use date of 6 months or less.◦ All other formulations have a 30-day beyond-use date

or duration of therapy, whichever date is earlier.

Beyond-Use Dating


A beyond-use date for a prescription of two or more active or inactive ingredients with varying expiration dates is trickier.

The beyond-use date is determined by taking 25% of the remaining expiration date or 6 months, whichever is earlier.

If dates differ, the earliest date is used. Examples 1 & 2 provide practice calculating

the beyond-use of non-sterile preparations. Conservative beyond-use dating guidelines in

USP Chapter <795> are most often used.

Beyond-Use Dating


Compounding pharmacies are seeking national accreditation to protect patents and business from legal challenges.

Pharmacy Compounding Accreditation Board (PCAB) – accreditation organization; provides quality and safety standards for voluntary accreditation.

Continuous quality improvement (CQI) – the process of written procedures in the PCAB standards designed to identify problems and recommend solutions.

Accreditation


Technicians in order to work in compounding pharmacies must obtain special certification and training.

Certification of Pharmacy Technicians:◦ Special certification (PCCA)◦ Training

Non-sterile Compounding Attire:◦ Clean protective clothing◦ Hairnet◦ Long lab coat◦ Disposable gloves◦ Eye goggles◦ Masks◦ Double gowning◦ Hand washing – liquid antimicrobial soap, minimum of 15

seconds

Regulations for Pharmacy Personnel


Documentation of all active and inactive ingredients, procedures for sequencing and mixing.

Master Control Record – the recipe. The master control record lists:

◦ Drug’s name, strength, and dosage form◦ Ingredients and quantities◦ Sequencing and mixing instructions

Includes the recommended beyond-use date, storage and labeling requirements.

Documentation of Non-sterile Compounding


Compounding log – generated for each prescription.

The compounding log is used to document calculations and any special equipment.

Prescription record – computer-generated copy of the log, stored and retrievable for future refills.

What is listed on the compounding log? Figure 8.2 pg. 322 in your book is an

example of a compounding log.

Compounding Log


Technicians must have a thorough knowledge of mathematical conversions and a good aptitude for performing calculations in a compounding pharmacy.

A double check by both the pharmacist and technician is strongly recommended to minimize medication errors.

All measurements and calculations must be documented and reviewed by the pharmacist during the final check of a compounded preparation.

Calculations in the Compounding Pharmacy


A variety of equipment is utilized in a compounding pharmacy.

Technicians need to be familiar with the equipment, its uses, and maintenance.

All materials needed for proper packaging and labeling must be ensured by the pharmacy technician.

Caution needs to be used for equipment in both sterile and non-sterile compounding pharmacies.

Equipment for Weighing, Measuring, and Compounding


Accurately weighing ingredients is one of the most essential parts of compounding.

Technicians must be comfortable using various balances when weighing products.

Familiarity with the device’s calibration is important when operating any type of balance.

Two-Pan Balances:◦ Class III prescription balance, Class A

prescription balance◦ Counterbalance

Measuring Devices for Solids


Weights are used for both measurement and calibration.

Pharmaceutical weights – a standardized set, used to offset the ingredient weight.

Weights are generally made of polished brass, and can be coated with a non-corrosive material.

Sets contain metric and apothecary weights. Typical sets are in grams, fractional grams (mg)

and avoirdupois weights. Weights are placed on the right pan; material to

be weight on the left pan.

Pharmaceutical Weights for Two-Pan Balances


Forceps – an instrument used for grasping and holding small objects; weights should be transferred using forceps not fingers.

A cloth should be used when handling larger weights.

Weighing paper – is placed on the pans to protect the balances from damage and to avoid contact between pharmaceutical ingredients and the metal trays.

Weighing boat – used to weigh larger quantities of chemicals.

Handling and Storage of Weights


Digital electronic analytical balance – uses a single pan and is easier to learn to use and more accurate than a Class III balance or counterbalance.

Operating an Electronic Balance:◦ Placed on a secure, level, and non-vibrating

service at waist height; perfectly level.◦ Calibration must be documented.◦ Avoid spilling.◦ Table 8.3 pg. 326 Steps for Using an Electronic

Balance

Digital Electronic Analytical Balance


Percentage of error – the acceptable range of variation above and below the target measurement of a bulk ingredient.

Determining percentage of error:◦ x 100 = percentage of error

The amount of error is the difference between the actual amount and the quantity desired:

Balances and Percentage of Error


Volumetric measurement – measuring of liquid volumes.

Graduated cylinders – a glass or polypropylene flask used for measuring liquids.

Conical graduates have wide tops and narrow bases and taper from top to bottom.

Cylindrical graduates are more accurate and have the shape of a uniform column.

Table 8.4 pg. 328 Measuring Liquid Volume

Measuring Devices for Liquids


Be sure the cylinder is on a flat surface. Read the volume measurement at the

bottom of the meniscus. Meniscus – the half-moon-shaped or

concave appearance of the upper surface of a liquid.

Measure at eye level, not by looking down on the container.

Viscous liquids may take longer to get an accurate measurement of the meniscus.

Using a Graduated Cylinder


Pipette – a long, thin, calibrated hollow glass tube that is used for accurate measurement and transfer of small volumes of liquid.

Oral Syringes and Droppers:◦ Oral syringes (hypodermic syringes without a

needle) can be used to measure large or small quantities of liquids.

◦ Oral syringes are more accurate when measuring thick, viscous liquids.

◦ Droppers can be used to transfer small volumes of liquid; droppers must be calibrated because the drop size will vary between liquids.

Measuring Devices for Liquids


Mortar and pestle – widely used in the compounding of liquids and solids.◦ Glass, porcelain, and Wedgwood.◦ Course-grained porcelain or Wedgwood is used for triturating (or

pulverizing)◦ Glass, with its smooth surface, is preferred for mixing liquids,

creams, ointments, and gels. Electric mortar and pestle is often used in a high-volume

compounding pharmacy. Beakers and Flasks – non-volumetric glassware.

◦ Can only approximate larger volumes of liquids; not used when an exact measurement of liquid is required.

Ointment Mill – three-roller mills mixes and reduces particle size.◦ Results in a smoother, more pharmaceutically elegant end

product.

Supplies for Making and Molding Ingredients


Ointment slab – compounding slab; made of ground glass.◦ Compounding may also be performed on special

disposable nonabsorbent parchment paper. Spatula – an instrument used for preparing

ointments and creams, loosening material from the surface of a mortar and pestle, transferring solid pharmaceutical ingredients.◦ Stainless steel, plastic, or hard rubber◦ Hard rubber spatulas are used with corrosive substances

Molds and Presses – to make rectal and vaginal suppositories or oral rapid-dissolving tablets and troches.

Supplies for Mixing and Molding Ingredients


Compounded products are stored in a variety of packages.

Most products will be in amber-colored vials or bottles.

Special packaging may be required. Topi-CLICK Delivery System:

◦ Used for delivery of topical creams◦ Holds up to 35 mL◦ Can provide 1-3 months of medication◦ Topi-CLICK delivery system promotes patient

compliance and has accuracy unmatched by the traditional tube delivery method

Containers for Packaging


Before preparing a compounded product the technician should have the master control record, ingredients, equipment, etc.

Adequate and uninterrupted time should be provided to the person compounding.

Utilizing the best technique for the mixing of active and inactive ingredients is something the technician must learn.

The best technique should be included in the master control record or suggested by the experienced compounder.

Techniques for Mixing Compounded Drugs


Comminution – the act of reducing a substance to fine particles.

Blending – the act of combining two substances. Trituration – the process of rubbing, grinding, or

pulverizing a substance to create fine particles.◦ Diluent powder – an inactive ingredient that is added

to the active ingredient when compounding a capsule. Levigation – a technique used when reducing

the particle size of a solid during the preparation of an ointment; a levigating agent – castor oil, glycerin, or mineral oil – is slowly added to the ingredients to wet (not dissolve) the insoluble substance.

Comminution and Blending


Pulverization – the process of reducing the size of particles in a solid with the aid of an additional ingredient in which the substance is soluble.

Spatulation – the process of combining and mixing substances by means of a spatula, generally on an ointment slab or tile.

Sifting – a process not unlike the sifting of flour in baking, using a wire mesh sieve.

Tumbling – used to mix powders in a resealable plastic bag or a glass bottle and “tumble” or rotate the container to mix the ingredients well.

Geometric dilution method – the most potent ingredient is added first, followed by the next most potent ingredient adding each time an amount equal to the amount in the mortar.◦ Example 4

Comminution and Blending


Powders – a finely divided combination, or admixture, of drugs and/or chemicals ranging in size from extremely fine to very coarse.◦ Goody’s Headache Powder, individually wrapped◦ Metamucil, bulk powder

Types of Powders: most active and inactive ingredients come in bulk powder form.◦ Size range: very coarse (No. 8 powder), coarse (No. 20

powder), moderately coarse (No. 40 powder), fine (No. 60 powder), or very fine (No. 80 powder).

Mixing of Powders: powders are combined by trituration, spatulation, sifting and tumbling, or automated equipment.◦ Example 5

Compounding of Specific Formulations


Rapid-dissolving tablets or troches are typically compounded in a special contained hood to minimize airborne contamination.

Rapid-dissolving tablets (RDTs) – unique tablet formulation that disintegrate rapidly and dissolve on the tongue within 30 seconds.

Troches – small, circular lozenges that contain active medication.

Tablets and Troches


A solid dosage form consisting of a gelatin shell that encloses the medicinal preparation, which may be a powder, granule, or liquid.

Hard-shell capsules standard sizes are 5,4,3,2,1,0,00,000 (smallest to largest).

Hard-shell capsules are meant to be swallowed whole; some can be opened and sprinkled on food or in drink.

Filling Capsules: ◦ Punch Method: used when hand-filling a capsule with

powder.◦ Capsule Machine: metal plates used to replace the one-at-a-

time punch-and-fill method; a capsule machine can make 100 capsules within a short time period.

◦ Example 6

Capsules


A liquid dosage form in which the active ingredients are dissolved in a liquid vehicle.

Solvent – the vehicle that makes up the greater part of a solution.

Solute – the ingredient dissolved in the solution.

Solutions can be aqueous, alcoholic or hydro-alcoholic.

Solutions


In a suspension, the active ingredient is not dissolved in the liquid vehicle but is rather dispersed throughout it.

What problem exists with suspensions? The auxiliary label “Shake Well” should

always be affixed to a suspension. Pediatric suspensions can be prepared that

are commercially unavailable. Example 7

Suspensions


Ointments: ◦ water-in-oil (w/o) emulsion that is occlusive,

greasy, and not water-washable. Creams:

◦ oil-in-water (o/w) emulsion that is nonocclusive, nongreasy, and water-washable.

Lotions: ◦ liquid suspension or oil-in-water emulsion used

topically.◦ Example 8

Ointments, Creams, and Lotions


Compounding Ointments, Creams, and Lotions: ◦ dermatologic therapies may call for combining

existing ointments or creams; dry powders may have to be added to an ointment or cream base.

Compounding Hormone Formulations:◦ Hormone replacement therapy (HRT) – combines

estrogen, progestin (female) and androgen (male) to relieve specific postmenopausal symptoms.

◦ Estrogen replacement therapy (ERT) – female hormones sometimes used in postmenopausal women and premenopausal women who have had complete hysterectomies.

Ointments, Creams, and Lotions


Solid dosage forms that are inserted into the body’s orifices, generally the rectum or vagina.

These dosage forms melt when exposed to body heat and fluids.

Suppositories are produced by molding and compression.

Patients should be advised to refrigerate the medication, why?

Suppositories


Each step of the compounding process is checked by the pharmacist and technician.

Table 8.6 Steps in the Compounding Process on pg. 344 outlines the steps required by USP Chapter <795>.

Selecting Medication Containers: ◦ Tablets and capsules should be stored in amber-

colored vials to protect the product from light.◦ Ointments and creams may be placed in white

ointment jars.◦ Suppositories and pellets may be dispensed in

cardboard boxes.

The Compounding Process


The compounded preparation must be labeled with all information for the consumer as required by state and federal governments.

The label should include:◦ Beyond-use date◦ Lot number◦ Date of compounding

Equipment should be cleaned and properly stored after use.

Hazardous chemicals should be disposed of in a proper manner.

Labeling and Cleanup


The pharmacist is legally responsible for the check of the final product.

What sort of things does the pharmacist verify as part of the final check?

Pharmaceutical elegance – or how the product looks.

Easy retrievability is important if there is a drug recall of any ingredients used in the compounded prescription.

Final Check by the Pharmacist


The patient needs to understand that his or her prescription has been individually prepared and compounded.

Patients should be made aware of the ingredients in the compound and how to take the medication.

Patients should be counseled on proper storage conditions as well as labeling requirements.

Patient Counseling by the Pharmacist


Insurances do not generally cover the cost of compounded medications.

The cost of a compounded medication is based on the time and experience of the compounder, and minimally on the active and inactive ingredients.

Some insurance companies will reimburse later on compounded prescriptions.

Success for reimbursement appears to be greater if the patient submits the claim, rather than the pharmacy.

Reimbursement


Remington: The Science and Practice of Pharmacy

Professional Compounding Centers of America (PCCA) http://www.pccarx.com/

United States Pharmacopeia (USP) http://www.usp.org

Secundum Artem: Current & Practical Compounding Information for the Pharmacist

International Academy of Compounding Pharmacists (IACP) http://www.iacprx.org/

Reference Sources for the Compounding Pharmacy

http://www.pccarx.com/

http://www.pccarx.com/

http://www.usp.org/

http://www.iacprx.org/


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Chapter 8 Created by Jennifer Majeske, Mineral Area College