Non-Sterile Compounding Basics

NOTICE (September 2019): This Technician Tutorial was developed to be consistent with recommendations from USP chapter <795>, which was revised on June 1, 2019. USP has since indefinitely postponed the effective date of this chapter, per this notice. Some of the content of this Technician Tutorial may be revised when USP re-releases this chapter.

Compounding a medication can help fill a gap when a commercially available product won’t fit the bill. Some reasons for compounding may include unavailability of a dose or strength, such as a high concentration of a pain med for a cancer patient, or unavailability of a dosage form, such as a topical formulation of a med that can have a local effect. When a commercially available product can be used, compounding should not occur.

Compounding can be an everyday occurrence in inpatient settings, where individualized doses of IV medications are prepared and specially made oral liquids may be needed for pediatric patients. On the other hand, requests for compounded meds might not be an everyday occurrence in some other pharmacy settings. However, providing this service can be a real convenience for patients who need it. And no matter if a non-sterile compound is prepared in an inpatient or outpatient setting, standards in USP Chapter <795> provide guidance to help ensure your patients receive a high-quality and safe preparation.

Spironolactone, 5.5 mg PO 98h x10d

Mrs. Oz presents this Rx for her 2-month-old daughter, Kaye. Kaye Oz was hospitalized for several weeks following birth, and was receiving this dose of spironolactone while hospitalized. The hospital pharmacy was preparing it when Kaye was an inpatient.

What is pharmacy compounding, and more specifically, non-sterile compounding?

Pharmacy compounding is performed in response to a prescription from a licensed prescriber to meet the immediate needs of an individual patient. The presence of this “triad” (prescription, prescriber, individual patient) is considered the main difference between compounding and manufacturing. Manufacturing generally involves preparing a product for resale by pharmacies, practitioners, or other persons.

Some compounded preparations must be sterile (completely free from bacteria or other contaminants) while others can be non-sterile. Products that must always be sterile include bronchial and nasal inhalations, baths and soaks for live organs and tissues, injectables, irrigations for wounds and body cavities, eye drops and ointments, and tissue implants.

A major difference between sterile and non-sterile compounding is that sterile compounding involves strict controls (e.g., air quality evaluation, sterility-testing of products, training and testing of personnel in aseptic technique). This is because contamination of sterile preparations can lead to significant patient harm.

However, similar to requirements for sterile compounding, training and annual competencies must be completed for non-sterile compounding. This must include hands-on demonstration of skills such as proper hand hygiene and garbing, measuring and mixing, and proper use of equipment, since there are also risks associated with non-sterile compounding.

Where can non-sterile compounding occur in the pharmacy?

Even though non-sterile compounding has less stringent requirements than sterile compounding in terms of environmental controls, a clean and sanitary area that’s designated by your pharmacy’s policies for non-sterile compounding, such as by a visible perimeter, is required. Plus, this area cannot have any carpet.

Work surfaces must be cleaned often (e.g., before compounding is started, when there are spills or if the area is visibly soiled, between compounding preparations with different ingredients, and after compounding is completed). While compounding is occurring, this space should not be used for other activities.

What are some commonly compounded non-sterile dosage forms?

Topical preparations (e.g., creams, lotions, ointments, pastes) and liquids for oral administration (e.g., elixirs, syrups, suspensions) are among the most commonly requested non-sterile dosage forms. Specific definitions of these are included in a glossary at the end of this document. Keep in mind that reconstitution of products according to the manufacturer’s instructions is not considered non-sterile compounding according to USP Chapter <795>. For example, adding 38 mL of water to a bottle of cefdinir powder for oral suspension to make 60 mL of cefdinir 250 mg/5 mL is not considered non-sterile compounding.

You show the Rx for Kaye Oz to the pharmacist. The pharmacist tells you that he does, in fact, have a recipe on file for spironolactone liquid. There is not a commercially available product that’s FDA-approved for children and babies.

Where do recipes for non-sterile compounds come from?

A recipe, or more specifically, a Master Formulation Record, is required for each non-sterile compound your pharmacy prepares. These documents will tell you exactly how to prepare a non-sterile compound.

A Master Formulation Record is required to include information, such as:

  • Name, strength, and dosage form of the compound
  • Ingredients and their amounts
  • What type of container and closure to use
  • How to prepare the compound, including what type of equipment and supplies will be needed
  • Physical description of the compound
  • Beyond-use date
  • Storage requirements
  • Labeling requirements
  • References

There are a number of places to get recipes for compounded preparations. Many pharmacies have a file of recipes. In addition, recipes might be found in a product’s package insert or by contacting the manufacturer, a local pharmacy school, or a drug information center. The USP-NF (United States Pharmacopeia-National Formulary) is a good source, as are other texts, like Trissel’s Stability of Compounded Formulations, and The Art, Science, and Technology of Pharmaceutical Compounding. Some websites, like www.compoundingtoday.com and www.mipedscompounds.org/standard-formulations, are good sources for recipes as well.

The pharmacist finds the recipe for spironolactone suspension, and hands a copy to you. The recipe includes the following information:

Spironolactone 5 mg/mL suspension

Spironolactone 50 mg tabs x 12
Purified water USP 5 mL
Cherry syrup, qs to 120 mL

Triturate tablets to a fine powder in a mortar and pestle.
Levigate with 5 mL of Purified Water USP to form a paste.
Add base solution in increasing amounts while mixing thoroughly.
Transfer contents of the mortar to a graduated cylinder.
Rinse the mortar and pestle with base solution and pour into graduated cylinder.
Add base solution to the graduated cylinder to achieve a total volume of 120 mL.
Transfer contents of the graduated cylinder into an appropriate size glass amber bottle.
Shake well to mix.

Beyond-use date: 28 days
Storage: Room temperature or refrigerate
Auxiliary labeling: Shake well before use

How do you calculate how much of the spironolactone suspension you will need to fill this Rx?

Determine how much compounded spironolactone liquid will be needed per dose using the ratio below:

5.5 mg/X mL = 5 mg/1 mL

Cross-multiply this ratio to solve for X [(1 mL) x (5.5 mg)] = [(5 mg) x (X mL)], so

X mL = [(1 mL) x (5.5 mg)]/(5 mg)

X = 1.1 mL

Since there are three doses each day, you need a total of 30 doses. Set up another ratio to calculate the total volume needed for the Rx.

1.1 mL/1 dose = X mL/30 doses

Cross-multiply this ratio to solve for X: [(1.1 mL) x (30 doses)] = [(1 dose) x (X mL)]

X mL = [(1.1 mL) x (30 doses)]/(1 dose)

X = 33 mL total to fill the Rx

If you need more information on performing calculations, get our two-part continuing education program that reviews these calculation procedures, Pharmacy Calculations for Technicians: Fundamentals of Math and Measures Part 1 and Pharmacy Calculations with Ratios and Proportions: Technician Math Part 2.

What must you do before you start compounding a non-sterile preparation?

Similar to sterile compounding, you must wash your hands with soap and water for at least 30 seconds. Make sure you go all the way up to your elbows. Dry your hands and arms thoroughly, then put on gloves. Gloves are the minimum requirement in terms of garbing, and you may need to wear other items such as a gown or mask, especially if a non-sterile compound includes meds that are considered hazardous. (In fact, check your pharmacy’s policy to see what is required when compounding with spironolactone, since this med may require extra garbing.) Change your gloves and any other garb at a frequency determined in your pharmacy’s policies.

What kind of equipment is used for compounding non-sterile preparations?

Prescription balances. Either a torsion balance or an electronic balance can be used to weigh materials for compounding (although torsion balances are being used less and less). A brass weight set is needed for the use of a torsion balance, and for calibrating an electronic balance. Weights should be handled with forceps, not fingers, to avoid scratching or soiling. Regardless of the type of balance you are using, materials to be weighed should be placed on weighing papers or in plastic weigh boats, and never directly on the balance.

Prescription balances should be placed on a flat surface and protected from drafts. When the lid of a balance is closed, free movement of the weighing pans should be permitted. The performance of balances should be checked and documented at least monthly.

Spatulas. Various sizes of stainless steel and plastic spatulas should be stocked in the compounding area. Small spatulas are good for handling dry chemicals. Larger spatulas are best for preparing or mixing large amounts of ointments or creams.

Pill tiles and ointment papers. Pill tiles, sometimes called ointment slabs, are handy for mixing ointments. Pill tiles can be preferable to ointment papers, which can tear when they become moist. For this reason, creams should never be prepared on ointment papers.

Graduates. Glass conical and cylindrical graduates (“graduated cylinders”) are used to measure the volume of liquids. When measuring a liquid, use the size of graduate with a capacity equal to or just over the volume you need. In fact, no less than 20% of the capacity of a graduate should be measured. This will help minimize the error in measurement. For example, if you measure 10 mL of OraSweet using a 100 mL graduated cylinder, the measurement is likely to be less accurate than if you use a 50 mL graduated cylinder.

Because measurements tend to be less accurate, conical graduates with a capacity of less than 25 mL should not be used for prescription compounding.

When measuring a liquid in a graduate, read the measurement at eye level, and at the bottom of the meniscus (the downward curve that the top of the liquid makes) for the best accuracy. If you are using a stirring rod, make sure to remove the stirring rod from the graduate before you “qs.” The stirring rod takes up space, so if you don’t take it out first, your total volume will come up short.

Mortars and pestles. Mortars and pestles come in different sizes, and can be made from materials like glass, porcelain, and Wedgewood. A glass mortar and pestle is best for liquids and for chemicals that are oily or will stain. A Wedgewood mortar and pestle is best for reducing the size of dry crystals and hard powder particles. Porcelain is smoother than Wedgewood and is best for blending powders and for pulverizing soft materials or crystals.

Here are some practical tips for using mortars and pestles:

  • Lightly dust the interior of a Wedgewood mortar with lactose to fill any crevices where crystals or powders might lodge.
  • Don’t interchange mortars and pestles if you don’t have to. They shape to each other over time. Switching them out might reduce contact between the head of a pestle and its mortar.

What special techniques are used for preparing non-sterile compounds?

When you are following a recipe, specific instructions might be given in terms that you are familiar with, like “crush” or “mix.” You might also encounter terms like “levigate,” “triturate,” etc. Definitions for these are included in the glossary at the end of this document.

The preparations you compound should be uniform in nature, so that each dose the patient takes or uses delivers the same amount of active drug. When you are crushing tablets or the contents of capsules for addition to a vehicle, you will generally want to produce a fine and uniform powder. You don’t want to see clumps or unevenness of color or texture in any preparation.

You choose the glass mortar and pestle to triturate the spironolactone tablets in. You crush the tablets, or “triturate” them, until you have a uniformly fine powder.

How should non-sterile compounds be dispensed and labeled?

In addition to usual prescription labeling requirements, labels for non-sterile compounds you are dispensing should also include:

  • Active ingredient and strength
  • Internal identification number of the compound
  • Dosage form
  • Amount in the container
  • Storage requirements, if other than controlled room temperature
  • Beyond-use date

The beyond-use date should be specified by the recipe that you are using. The maximum beyond-use date is dictated by USP Chapter <795>. Most compounds will have shorter beyond-use dates, such as 14 days, but the max expiration date for any non-sterile compound according to this guidance is 180 days. Keep in mind that beyond-use dates are often based on the nature of the formulation (e.g., whether it’s water-based), its storage conditions, its packaging, etc.

Suspensions will require a “shake well” label. Topical preparations will require an “external use only label.” “Refrigerate” labels might be required for either oral or topical preparations. Check your Master Formulation Record to find this out.

After you finish preparing the spironolactone suspension, you place it in a glass amber prescription bottle. You place the ingredients that you used to compound it on the counter for the pharmacist to check. You also put a prescription label on the bottle for Kaye Oz, and include a 28-day expiration date, as well as an auxiliary label to “Shake Well” as indicated by the recipe. Finally, you thoroughly clean the equipment that you used.

If you were preparing this med for Kaye in a hospital, you would have drawn up each 1.1 mL dose into an amber oral syringe for dispensing, probably just a 24-hour supply at a time, with appropriate labeling.

What records must be kept for non-sterile compounds?

Records of compounding activities must be kept as required by your state, which may be dictated by USP Chapter <795>. Besides a Master Formulation Record for each non-sterile compound your pharmacy prepares, you must create a Compounding Record each time you prepare a non-sterile compound, to document your activities. The person who checks the compound must document their name and date of review on the Compounding Record.

A Compounding Record must include information, such as:

  • Name, strength, and dosage form of the compound
  • Date and time of preparation
  • Rx or internal lot number
  • Who was involved in preparing the compound
  • Sources, lot numbers, and expiration dates of ingredients used, and actual quantities measured/weighed
  • Quantity compounded
  • Beyond-use date
  • Reference to a Master Formulation Record

According to USP <795>, a Compounding Record and Master Formulation Record must be kept on file for at least three years, for each compound prepared. Additionally, the Certificate of Analysis or COA (from the wholesaler) for bulk ingredients used in the compound should also be kept on file for at least three years. But check your pharmacy’s policies and procedures, to ensure you are in compliance with your state’s laws.

Glossary of Compounding Terms

DOSAGE FORMS

  • Cream: an opaque soft solid or thick liquid intended for external application. A cream is an emulsion, which means that there is one “phase” dispersed throughout another, like oil-in-water or water-in-oil. Some commonly used cream bases are Dermabase, Eucerin, Hydrocream, and Vanicream.
  • Elixir: a clear, sweetened, water-alcohol mixture that is usually flavored and suitable for drugs that do not dissolve in water alone. Elixirs are usually less sweet and less viscous (thick) than syrups and are generally less effective in masking taste.
  • Gel: a semisolid dosage form consisting of particles or molecules suspended throughout a liquid. Liquaphor is a commercially available gel base.
  • Lotion: a fluid suspension for external application. Like creams, lotions are emulsions. In fact, creams can sometimes be made into lotions.
  • Ointment: a semisolid preparation for external application to the skin or mucous membranes that softens or melts at room temperature. Some commonly used ointment bases are Aquabase and Aquaphor, polyethylene glycol, white ointment, and white petrolatum.
  • Paste: a thick, stiff ointment.
  • Solution: a liquid preparation containing one or more drug substances in a solvent or mixture of solvents. Syrups and elixirs are both types of solutions.
  • Suspension (for oral administration): a sweetened, flavored, liquid preparation containing the active drug “suspended” in a liquid vehicle. Syrup vehicles, like cherry syrup, can be used to prepare suspensions. Ora-Plus and Suspendol-S are commonly used commercially available suspending agents.
  • Syrup: a concentrated, water-based preparation of a sugar or sugar substitute with or without flavoring agents and medicinal substances. Syrups can serve as pleasant-tasting vehicles for drugs. Cherry syrup, Ora-Sweet, and Ora-Sweet SF are examples of commercially available vehicles for syrups.

TECHNIQUES

  • Geometric dilution: a method to ensure that small quantities of ingredients, usually potent drugs, are uniformly distributed throughout a mixture. This usually involves a series of dilution steps, where more and more vehicle is added to a drug, with thorough mixing between each step.
  • Levigation: reducing the particle size of a solid by triturating it in a mortar or spatulating it on an ointment slab or pad with a small amount of liquid in which the solid does not dissolve.
  • Spatulation: mixing on an ointment slab or pad using a spatula.
  • Trituration: reducing a substance to fine particles by rubbing it in a mortar with a pestle.

Project Leader in preparation of this technician tutorial (350880): Stacy A. Hester, RPh, BCPS, Associate Editor

Cite this document as follows: Technician Tutorial, Non-Sterile Compounding Basics. Pharmacist’s Letter/Pharmacy Technician’s Letter. August 2019.

Please continue to the next section for a “Cheat Sheet” of non-sterile compounding basics

“Cheat Sheet” for Non-Sterile Compounding Basics

What is pharmacy compounding, and more specifically, non-sterile compounding?

Pharmacy compounding involves preparing a med for a patient in response to a prescription from a prescriber. Non-sterile compounding applies to meds that aren’t required to be sterile, such as an oral liquid. This is in contrast to meds that must be sterile, such as IV injections.

What are some commonly compounded non-sterile dosage forms?

Some commonly compounded non-sterile dosage forms include oral liquids such as syrups and suspensions, and topicals such as creams or ointments.

Where do recipes for non-sterile compounds come from?

Recipes are actually officially referred to as Master Formulation Records. These documents have detailed information about how to prepare a compound. Your pharmacy may have a file of these. Drug information centers, drug manufacturers, schools of pharmacy, and textbooks are other potential sources of recipes.

What must you do before you start compounding a non-sterile preparation?

Before you start compounding a non-sterile preparation, you must wash your hands up to the elbows with soap and water for 30 seconds, dry off, and put on gloves. You also must ensure you are compounding in your pharmacy’s designated area, and clean that area before you start compounding.

What kind of equipment is used for compounding non-sterile preparations?

A number of different types of equipment are used for non-sterile compounding. These include prescription balances, mortar and pestle, and graduated cylinders. You’ll be required to do training and an annual hands-on competency to show you know how to use them properly.

What special techniques are used for compounding non-sterile preparations?

You may be required to simply “crush” or “mix” as part of the process for preparing a non-sterile compound. Other terms such as “levigate” or “triturate” might also be used. You’ll need to be trained in these techniques prior to preparing certain non-sterile compounds.

How should non-sterile compounds be dispensed and labeled?

Non-sterile compounds require extra information besides what’s on a prescription label. For instance, you’ll need to make sure the med, strength, and dosage form are on the label, as well as a beyond-use date for the compound, and an internal identification number.

What records must be kept for non-sterile compounds?

A Master Formulation Record, Compounding Record, and Certificate of Analysis (COA) must be kept on file for each non-sterile compound prepped. USP standards require keeping these on file for at least three years. However, your state might have different requirements, so check your pharmacy’s policies and procedures.

[August 2019; 350880]

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