RxCe - Essential Nonsterile Compounding Techniques Materials

ESSENTIAL NONSTERILE COMPOUNDING TECHNIQUES

Faculty:

Liz Fredrickson, PharmD, BCPS

Liz Fredrickson, PharmD, BCPS, is an Associate Professor of Pharmacy Practice and Pharmaceutical Sciences at the Northeast Ohio Medical University (NEOMED) College of Pharmacy, where she is course director of the Parenteral Products and Basic Pharmaceutics Lab courses.

Pamela Sardo, PharmD, BS

Pamela Sardo, PharmD, BS, is a freelance medical writer and licensed pharmacist. She is the founder and principal at Sardo Solutions in Texas. Pam received her BS from the University of Connecticut and her PharmD from the University of Rhode Island. Pam’s career spans many years in retail, clinics, hospitals, long-term care, Veterans Affairs, and managed health care responsibilities across a broad range of therapeutic classes and disease states.

Abstract

Pharmaceutical compounding involves preparing medications tailored to an individual’s specific health needs. Pharmacy technicians who compound nonsterile medications should be well-versed in compounding standards and skilled in the techniques required to prepare medications that are effective, safe, and high-quality. This continuing education program will review techniques for compounding nonsterile preparations, including particle-size reduction, weighing, and mixing. Additionally, techniques for preparing capsules, tablets, solutions, suspensions, suppositories, ointments, and lozenges will be described. The process of assigning beyond-use dates to CNSPs will also be discussed.

Accreditation Statements

In support of improving patient care, RxCe.com LLC is jointly accredited by the Accreditation Council^TM for Continuing Medical Education (ACCME^®), the Accreditation Council for Pharmacy Education (ACPE^®), and the American Nurses Credentialing Center (ANCC^®), to provide continuing education for the healthcare team.

Joint Universal Activity Number: The Joint Accreditation Universal Activity Numbers assigned to this activity are as follows:

Pharmacists: JA4008424-0000-26-074-H07-P

Pharmacy Technicians: JA4008424-0000-26-074-H07-T

Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit.

Credit Types:

Pharmacy - 2 Credits

Type of Activity: Knowledge

Media: Computer-Based Training (i.e., online courses)

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Activity Pre-Test, Post-Test, and Activity Evaluation.

Release Date: May 23, 2026 Expiration Date: May 23, 2029

Target Audience: This educational activity is for Pharmacists and Pharmacy Technicians

How to Earn Credit: From May 23, 2026, through May 23, 2029, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Take the “Educational Activity Pre-Test;”

Study the section entitled “Educational Activity;” and

Complete the Educational Activity Post-Test and Activity Evaluation. The Educational Activity Post-Test will be graded automatically. Following successful completion of the Educational Activity Post-Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

CE and CME Credits: Credits for this course will be uploaded to CPE Monitor^® for pharmacists and pharmacy technicians. Physicians may receive AMA PRA Category 1 Credit™️ and use these credits toward Maintenance of Certification (MOC) requirements. Physician Assistants may earn AAPA Category 1 CME credits, reportable through PA Portfolio. All learners shall verify their individual licensing board’s specific requirements and eligibility criteria.

Statement of Need

Compounding nonsterile preparations remains a foundational skill for pharmacists and pharmacy technicians. Variability in training and practice standards remains. This variability can lead to inconsistencies in product quality, safety, and compliance with USP <795> guidelines. Practice gaps persist in accurate weighing techniques, particle-size reduction, and appropriate mixing methods. These factors all directly impact drug stability and therapeutic effectiveness. Determining beyond-use dates and selecting appropriate dosage forms requires applied knowledge that is often underdeveloped. This activity aims to address these gaps and strengthen competencies by reinforcing best practices in nonsterile compounded preparations, including weighing accuracy, formulation techniques, and beyond-use date determination, and by improving regulatory compliance and enhancing patient safety.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Describe techniques used to reduce particle size and mix ingredients for a compounded nonsterile preparation (CNSP)

Demonstrate appropriate methods by which to weigh components of a CNSP properly

Determine beyond-use dates for CNSPs

Compare and contrast techniques used to prepare capsules, tablets, solutions, suspensions, suppositories, ointments, and lozenges

Disclosures

The following individuals were involved in planning, developing, and/or authoring this activity: Liz Fredrickson, PharmD, BCPS; and Pamela Sardo, PharmD, BS. None of the individuals involved in developing this activity has a conflict of interest or financial relationships related to the subject matter. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity.

Educational Activity Pre-Test

Which of the following is a manual comminution method that involves grinding solids into a fine powder while mixing?

Levigation

Pulverization by intervention

Geometric dilution

Trituration

Which of the following best describes an appropriate manual mixing technique?

Use of a V-blender or turbula mixer

Adding all ingredients at once and mixing thoroughly

Use of a mortar and pestle or spatula with geometric dilution

Use of resonant acoustic mixing

What is the maximum beyond-use date that can be assigned to a compounded nonsterile preparation (CNSP) according to USP <795>?

90 days

120 days

180 days

365 days

Educational Activity

Essential Nonsterile Compounding Techniques

Highlights

Compounding personnel should apply appropriate particle-size reduction methods (e.g., trituration, levigation) to ensure uniformity and stability

Proper mixing techniques should be used to achieve homogeneity, including geometric dilution and appropriate selection of manual or mechanical methods

Accurate weighing techniques are essential for dose precision, including the correct use of torsion and electronic balances

The selection of compounding technique should be based on dosage form and ingredient properties, including solubility, particle size, and stability

Dosage form–specific techniques vary across preparations, including capsules, solutions, suspensions, ointments, suppositories, and lozenges

Common compounding errors (e.g., improper mixing or inaccurate weighing) can lead to dose variability and therapeutic failure

Beyond-use dates (BUDs) should be assigned conservatively based on formulation characteristics, stability, and risk of contamination

Factors such as water activity, microbial growth risk, and container compatibility should be considered when determining BUDs

Introduction

Pharmaceutical compounding involves preparing medications tailored to an individual’s specific health needs. Pharmacists and pharmacy technicians who compound nonsterile medications should be well-versed in compounding standards and skilled in the techniques required to prepare medications that are effective, safe, and high-quality. This continuing education program will review techniques for compounding nonsterile preparations, including particle-size reduction, weighing, and mixing. Additionally, techniques for preparing capsules, tablets, solutions, suspensions, and lozenges will be described. The process of assigning beyond-use dates will be discussed.

General Compounding Techniques for Nonsterile Preparations

Personnel must be trained in fundamental compounding techniques, including particle-size reduction, weighing, and mixing, to properly prepare compounded nonsterile preparations (CNSPs).^1,2 Perfecting these skills will help ensure that preparations are compounded accurately.

Particle Size Reduction

Particle size reduction is also called comminution.¹ This technique ensures ingredients are reduced to a consistent particle size, promoting uniformity and stability.¹ Manual comminution methods include trituration, levigation, and pulverization by intervention, and mechanical methods involve using ball mills, grinders, and coffee mills. Manual comminution methods are defined in Table 1.¹ The chosen method will depend on the characteristics of the API.¹ Pulverization is preferred for gummy-type materials, while levigation may be best for reducing the particle size of insoluble materials included in ointment or suspension preparations.¹ Trituration is preferred to reduce the particle size of hard, fracturable powders.¹

Table 1

Manual Comminution Methods¹

Term	Definition
Trituration	Grinding solids into a fine powder while simultaneously mixing
Levigation	Grinding an insoluble substance to a fine powder while wet
Pulverization by intervention	An intervening solvent is used to dissolve the compound, and this is mixed to enhance the evaporation of the solvent

In addition to understanding which method to use, compounding personnel must select the appropriate equipment to perform comminution. For example, glass mortars should be used to comminute potent materials, as they are nonporous and will prevent drugs from remaining in the mortar pores.¹ Otherwise, the dose of the formulation may be affected.¹

Mixing Ingredients

Proper mixing ensures homogeneity and consistent dose distribution.¹ Uniformity is critical, as improper mixing or particle size variation can lead to dose inconsistency and therapeutic failure. Compounding personnel may choose to use random mixing or ordered mixing strategies.¹ Random mixing occurs when every individual particle can move independently and randomly.¹ Random mixtures are detailed in Table 2.¹ Ordered mixing involves mixing small, cohesive particles to ensure homogeneity is achieved.¹ In ordered mixing, the ordered unit moves as a whole instead of as individual particles.¹

Table 2

Random Mixtures¹

Mixture	Details
Free-flowing mixtures	Segregation of individual components during further processing in dosage form preparation
Cohesive mixtures	Not free-flowing The individual agglomerates of particles must be repeatedly broken down and allowed to redistribute within the system to ensure a satisfactorily mixed product
Ordered mixtures	Mixing of a fine, micronized form with larger carrier particles, and the small particles adhere to the large particles, where they are tightly held on the surface of the carrier particles

Mixing methods can also be categorized as either manual or mechanical.¹ Manual methods include geometric dilution, while mechanical methods include tumbling and resonant mixing.¹ Geometric dilution is a manual mixing method that starts by adding the ingredient of the smallest quantity to your mortar.¹ Other ingredients are then added to the mixture in order of quantity required by doubling the portion being mixed each time.¹ Ultimately, the primary objective in mixing ingredients using geometric dilution is to achieve homogeneity in the final preparation, which is essential for optimal therapeutic outcomes. Mechanical methods are detailed in Table 3.¹

Table 3

Mechanical Mixing Methods¹

Method	Details
V-Blender	Involves tumbling the powders in a rotating chamber designed to enhance the mixing process
Triple V-Blender	Consists of three individual chambers attached to the blender power unit Allows up to three different blending processes to be conducted simultaneously
Turbula Mixer	Used to obtain a homogeneous mixing of powders with different specific weights and particle sizes Particles are then mixed in a closed container
Resonant Acoustic Mixing Technology	Uses low-frequency, high-intensity acoustic energy to establish a uniform shear field throughout the entire mixing container, resulting in rapid fluidization (movement) and dispersion of the material Oscillating mechanical driver generates motion in the mechanical system that is then acoustically transferred to the material to be mixed

Manual mixing equipment includes a mortar and pestle (Figure 1) or a pill tile with a spatula (Figure 2).¹

Figure 1

Mortar and Pestle

Figure 2

Pill Tile and Spatula

Case Example

A pharmacy technician prepared capsules without using geometric dilution, resulting in uneven distribution of the active ingredient. Several capsules contained subtherapeutic doses, while others exceeded the intended dose. The patient experienced inconsistent therapeutic effects, requiring intervention. This highlights the importance of proper mixing techniques to ensure dose uniformity and patient safety.

Weighing Components

Accurate weighing is essential to ensure the correct dose and quality of the final preparation.¹ Compounding personnel may choose to utilize a torsion or electronic balance.¹ Use of these balances requires different steps, which are detailed below. The following are steps to use a torsion balance:¹

Position the balance on a flat, level surface away from air currents

Ensure the weigh-beam rider or the dial-in weights are at the zero position

Using leveling feet, bring balance into equilibrium

Place weighing paper or dish on each balance pan

Repeat the process of bringing balance into equilibrium

During the entire weighing process, keep the balance pan arrested when adding anything to the pan

Add the appropriate external and dial weights to the balance. External weights are added to the right-hand balance pan

Use a spatula to add material to be weighed to the weighing paper or dish on the left-hand balance pan

Release the arresting mechanism and observe the balance point to determine if you have transferred the desired amount of material

If pans are not balanced, arrest the pans before adding or removing material. Repeat the previous steps until equilibrium has been reached

Arrest balance pans and remove weights

Clean the balance

The following are steps to use with an electronic balance:¹

Position the balance on a flat, level surface away from air currents

Turn the balance on and press the tare button

Place weighing paper or a dish on the balance pan

Press the tare button again to tare out the weight of the weigh paper or dish

Use a spatula to add material to the weigh paper until the desired weight is obtained

Clean balance when finished

Common Pitfalls in Nonsterile Compounding

Inadequate particle-size reduction leading to poor uniformity

Improper mixing resulting in dose variability

Failure to use geometric dilution when required

Inaccurate weighing due to improper balance use

Overfilling or underfilling capsules

Failure to consider solubility when preparing solutions

Dosage Form-Specific Techniques

Techniques for preparing various dosage forms are described below.

Tablets

Tablets are a common oral dosage form due to their stability and effectiveness.¹ Tablets can be molded, sintered, or compressed.¹ To prepare molded tablets, the active drug is mixed with a diluent like lactose or mannitol as the base, and lactose is often preferred.¹ Once the tablet mixture is ready, the mass should be moistened and then pressed into the tablet mold cavities using a spatula.¹ The cavity plate can then be set on the peg plate, with pegs aligned.¹ This is then allowed to drop, which pushes out the tablets.¹ The tablets should be left to dry, and then can be removed and packaged.¹

Capsules

Capsules are generally prepared as hard or soft-shell capsules, each with a different purpose.^3-5 Softshell capsules, also called softgels, may contain nonaqueous liquid or semisolid formulations.³ Ingredients in softgels include gelatin, water, and additives such as colorants.³ Hard shell capsules are two-piece shells that may be filled with powders, pellets, granules, non-aqueous solutions, suspensions, or semi-solids.³ The two components of the hard shell include the base (or body) and the cap.³ The base is longer, has a small diameter, and holds the capsule contents.³ The cap is shorter and slightly larger and slides over the base to form a snug seal.³

The Rule of Sixes can be used to estimate appropriate capsule size and fill weight.^1,4 This is detailed in Table 4 below.^1,4 Patient considerations, such as whether the patient can swallow a particular size capsule, should also be considered when selecting the capsule size.^1,4

Table 4

Rule of Sixes ^1,4

1.	Set up six “6s.”	6	6	6	6	6	6
2.	List the capsule size.	0	1	2	3	4	5
3.	Subtract values in step 2 from those in step 1 to determine the average fill weight in grains.	6	5	4	3	2	1
4.	Convert fill weight to grams (1 grain = 0.065 g).	0.390	0.325	0.260	0.195	0.130	0.065
5.	Determine fill volume in milliliters	0.67	0.50	0.37	0.30	0.21	0.12
6.	Calculate and list average capsule fill density (divide weight values in step 4 by volume values in step 5).	0.58	0.65	0.70	0.65	0.62	0.54

Two methods are widely used to prepare capsules: individual hand filling and capsule machine filling.^1,3,4 Regardless of the method, compounding personnel must first determine the ingredients they will utilize to prepare and fill the capsules.^1,3,4 Sources of APIs may include pure drug powders or can be obtained from manufactured tablets, capsules, or liquids.¹

The first step in preparing powders for capsules is accurately weighing and/or measuring each ingredient.¹ In general, compounding personnel should aim to prepare an additional capsule or 5% to 10% more of the intended formulation.¹ This extra quantity will help account for any potential powder loss during the compounding process.¹ After weighing and measuring, the next step is particle size reduction. This is followed by sieving the mixture using mesh.¹ The size utilized may range from Nos. 60 to 100, depending on the specific powders used.¹ This process will further refine particle size.¹ Powders can then be mixed using geometric dilution.

When hand-filling capsules, precise techniques will ensure accurate dosing and formulation integrity.¹ The process begins by arranging the powder into a pile using a spatula, ensuring that the pile’s thickness is approximately one-third the length of the capsule body.¹ It is very important that direct contact between personnel’s hands and the powder is avoided while punching the capsules. Wearing gloves will minimize contact.¹ During the filling process. The capsule should be pressed into the powder on the working surface while gently rotating to pack the powder evenly.¹ A slight resistance will be sensed as the capsule is pressed through the powder, indicating it is full.¹ After filling, the capsule's weight should be checked, and the powder amount should be adjusted to achieve the desired weight.¹ One issue that may occur during this process is powder not adhering well within capsules during punching.¹ This can be mitigated by placing the capsule base on its side and using a spatula to guide or fill the powder.¹ It is important to avoid scraping or scratching the capsules during this process.¹

Personnel can use automated capsule-filling machines as an alternative approach to hand-filling.¹ During this process, empty gelatin capsules with the cap on top are inserted into the machine.¹ The machine then separates the capsule base from the cap, and the part of the machine holding the caps is removed.¹ The capsule bases will drop into position, aligning the top of the base with the working surface.¹ Next, the powder mixture is spread evenly over the working surface, using a plastic scraper held perpendicular to the plate to allow the powder to fall naturally into the empty capsule bases by gravity.¹ It is important not to push the powder into the capsule shells with the scraper, as this can lead to inconsistent quantities of powder in each shell.¹ A specialized tamper is used to compress the powder in the shells.¹ Before tamping, the excess powder is moved aside, and the tamper is applied to the cleaned area. The tamping process is repeated as needed until all capsules are filled evenly.¹ Once capsules are filled, the part of the machine holding the caps is placed over the machine.¹ The capsules are then capped and can be removed.¹

After they have been prepared, capsules should be cleaned.¹ This can be done by placing the capsules in a folded cloth or a container with sodium bicarbonate, sugar, or salt.¹ The cloth or bag can then be gently rolled, passing the contents through a No. 10 sieve, which allows the salt but not the capsules to pass through.¹

Solutions

Solutions are the most common liquid dosage form.¹ The complexity of a solution's composition can vary widely and depends on factors such as the APIs, intended use of the preparation, patient characteristics, and storage conditions.¹ Formulations for preparing solutions typically consist of the API and excipients such as cosolvent systems, flavorings, sweeteners, colorings, preservatives, buffering agents, antioxidants, or other additives.¹ When choosing a solvent, it is recommended to use official solvents listed in the United States Pharmacopeia/National Formulary (USP-NF).¹ Compounding personnel should also remember that polar solutes will dissolve in polar solvents, and nonpolar solvents should be used to dissolve nonpolar solutes.¹

Improper solvent selection or pH adjustment may result in precipitation or reduced drug efficacy.

pH is an important consideration when preparing a solution, as this can affect drug solubility, activity, absorption, and stability.¹ Certain drugs will precipitate in the solution when the pH falls outside the intended range.¹ Selecting the appropriate vehicle for the solution is also a key consideration.¹ Various vehicles can be used in oral solutions, with ethanol, glycerin, syrups, and water being the most common.¹ Compounding personnel can reference the USP/NF for many types of water, including pharmaceutical waters.¹

Various techniques are employed in preparing oral solutions. A simple solution is most commonly prepared by dissolving a drug in a solvent.¹ This process may only require stirring, but other times, heat or agitation may be required for the solution to form.¹ Tips and tricks for compounding solutions are detailed in Table 5.¹

Table 5

Tips to Compound Solutions¹

Stir preparations gently to avoid foaming

Magnetic stirrers and blenders can be used to save time and help prepare homogeneous preparations

Do not use a stirring rod when adding “sufficient volume” of a solvent to a graduate in which you are preparing the solution

Liquid filtration can help to produce a clear preparation

Always know the pH and alcohol concentrations of preparations you are compounding

Preservative effectiveness can be related to pH

Dissolve salts in small quantities of water before adding a viscous vehicle

When combining two liquids, stir the mixture constantly to decrease the chance of incompatibilities resulting from concentration effects

Suspensions

Suspensions are valuable dosage forms that enhance the stability of drugs that are unstable in solution.¹ Suspension formulations typically contain insoluble particles, a liquid medium, a surfactant or viscosity enhancer, and a preservative.¹ The sequence in which these components are combined can significantly impact the stability of the final preparation.¹

Compounding a suspension begins with achieving uniform, fine particles of the drug.¹ Once particle size reduction is accomplished, it is crucial to thoroughly wet the API before blending it with the vehicle.¹ Hydrophilic materials are effectively wetted using water-miscible liquids like glycerin, while hydrophobic substances can be wetted using nonpolar liquids or surfactants.¹ It is considered best practice to use the smallest amount of wetting agent necessary. Once the drug and wetting agent have been mixed to form a thick paste, the vehicle is added while stirring continuously.¹

Viscosity is key to keeping APIs in suspension, and viscosity-increasing agents should be gradually added to water while vigorously stirring the mixture and maintaining stirring throughout hydration.¹ Alternatively, these agents can be mixed with a water-soluble substance like sucrose before incorporating them into water, or a paste can be made with a water-miscible liquid before addition to water.¹ Some agents may require initial dispersion in hot water followed by the addition of cold or ice water to minimize clumping, especially with polymers that tend to clump and complicate the preparation process.¹

These methods support the formation of stable, well-dispersed suspensions.¹ Compounding personnel should also observe suspensions for resuspendability and determine if they have caking tendencies.¹ Poor resuspendability can lead to inconsistent dosing and reduced therapeutic effectiveness. Further, suspensions should not be too thick, as this can affect the pourability of the preparation.¹

Ointments

Ointments are a type of semisolid dosage form that is used to deliver medications topically to the skin.¹ Compounding personnel can use manual or mechanical methods to prepare ointments.¹ Generally, ingredients will be added to a commercially prepared ointment base.¹ To manually prepare an ointment, personnel can use either a mortar and pestle, pill tile and spatula, or an ointment pad.¹ No matter which equipment is used, it should be cleaned and dried before use.¹ Mixers are used to prepare large amounts of ointment mechanically.¹ General tips for preparing ointments are detailed below.¹

Combine two or more ointments by mixing them in a plastic bag

Transfer ointments directly from plastic bags into tubes by cutting one corner of the plastic bag and squeezing the contents into the ointment tube or jar

Volatile solvents should not be used to levigate powders because the solvent will evaporate and leave crystals of the drug

When oil and aqueous phases are mixed, heat the aqueous phase to a few degrees above the oil phase. Heating before mixing is helpful, as the aqueous phase tends to cool faster than the oil phase.

Cool ointments to just a few degrees above solidification before pouring them into tubes or jars. This minimizes the layering of the ointment in the packaging.

Heat softens ointments, making it easier to fill jars and tubes. Heating must be done cautiously to prevent stratification of the ingredients.

When preparing a base, the ingredient with the highest melting point should be melted first, and then the heat should be gradually reduced. The remaining ingredients should be added in order of increasing melting point until a uniform mixture is obtained. This process will enhance the stability of the final product by ensuring the ingredients are exposed to the lowest possible temperature during preparation.

If a water-containing base is used and the drug is water-soluble, the drug should be dissolved in a minimum quantity of water before incorporating it into the base

Inadequate mixing or phase separation may compromise drug distribution and stability.

Suppositories

Suppositories are a type of solid dosage form used to deliver medication either through the rectum, vagina, or urethra.¹ Three methods used to prepare suppositories include hand molding, fusion, and compression, with molding and fusion being more common.¹ The general steps of preparing suppositories include preparing and calibrating the mold, preparing the base of the suppository, preparing the active ingredient, mixing and pouring, and finally cooling the suppositories and packaging them.¹ Hand molding and fusion will be discussed in more detail.¹

Hand molding is useful because it does not involve heat; instead, it uses cocoa butter, which is easy to handle at room temperature.¹ With hand molding, the compounder will grate the cocoa butter and then add the active ingredient.¹ These ingredients are combined, and the mixture is pressed to form a cylindrical shape.¹ The diameter of the cylinder depends on the size of the suppositories being prepared.¹ Once this is formed, the compounder will cut it into appropriate sizes, round the tips of the suppositories, and then package and label the preparation.¹

The fusion method involves heating the base ingredient and mixing in excipients and the active ingredient.¹ This melted mixture is poured into the suppository molds and cooled.¹ The suppositories are then removed, trimmed, and packaged.¹

Before using the fusion method, the suppository mold must be calibrated.¹ This can be done using the steps below.

Prepare the suppository molds and confirm that the cavities are clean and dry.

Obtain and melt enough suppository base to fill 6 to 12 molds.

Pour the base into the molds, cool, and trim.

Remove the suppositories and weigh.

Divide the total weight by the number of blank suppositories prepared to obtain the average weight of each suppository for this particular base.

Use this weight as the calibrated value for that mold with that lot of suppository base.

Lozenges

Various types of lozenges may be prepared, including hard lozenges, soft lozenges, and chewable lozenges.¹ Hard lozenges have firm candy bases derived from sugar and syrup and frequently incorporate adhesive agents like acacia.¹ Soft lozenges typically rely on a polyethylene glycol (PEG) base, while chewable varieties utilize a glycerinated gelatin base.¹

The preparation of lozenges involves molding a carbohydrate mixture into hard candies, forming a soft lozenge matrix, or molding a gelatin base into a chewable mass.¹ Each method has its own associated process. For hard lozenges, sugar and other components are heated to the appropriate temperature, poured into molds, or pulled into ribbons as they cool, then cut to the desired length.¹ Alternatively, they can be compressed into very hard tablets using commercial methods.¹ Soft and chewable lozenges are prepared using molds that require calibration to determine the weight of each lozenge based on the specific base used (Figure 3).¹ This calibration involves melting the lozenge base, pouring it into molds, cooling the blank lozenges, weighing them, and then calculating the average weight per lozenge.¹ Another method involves pouring the lozenge mixture onto the work surface to form a sheet of uniform thickness, then punching out the lozenges.¹

Figure 3

Lozenge Mold

Assigning Beyond Use Dates

The term beyond-use date (BUD) refers to the date (or hour and date) after which a compounded nonsterile preparation (CNSP) cannot be used and must be discarded.² Guidelines for assigning beyond-use dates are provided by the United States Pharmacopeia (USP).² The BUD can be calculated in terms of hours, days, or months.² Before learning more about what a BUD is, it can be helpful to understand what it is not. The most important distinction is recognizing the differences between a BUD and an expiration date. These terms are compared in Table 1. An expiration date is the period during which a conventionally manufactured product, active pharmaceutical ingredient (API), or added substance is expected to meet the requirements of a compendial monograph or maintain expected quality when kept under the prescribed storage conditions.² An expiration date limits the time during which manufactured products can be dispensed or used.² Beyond-use dates are typically much shorter than expiration dates and do not require the extensive testing needed for expiration dating.²

Factors Impacting Beyond-Use Dates

It is recommended to assign beyond-use dates to CNSPs conservatively; this helps ensure the product remains safe and effective during use and storage and minimizes the risk of contamination or degradation. In the process of establishing a beyond-use date, there are numerous factors to consider, including:²

The chemical and physical stability properties of the active pharmaceutical ingredient (API)

The chemical and physical stability of any added substances (excipients) in the preparation

The compatibility of the container closure system with the finished preparation

The degradation of the container closure system, which can lead to a reduction in the integrity of the CNSP

The potential for microbial growth in the CNSP

Any significant deviations from essential compounding steps and procedures, such as changes to essential compounding steps, may have an impact on the stability of the formulation

Beyond-Use Dating Guidelines

Table 6 details water activity values, and Table 7 provides the most recent beyond-use dating recommendations from USP <795>, including the type of preparation, its associated BUD, and recommended storage temperature.² In terms of temperature, controlled room temperature (CRT) is defined as 25⁰C, and refrigerated temperature is between 2⁰C and 8⁰C.²

When preparing CNSPs, personnel should note that both materials and equipment contribute to the risk of microbial growth in the final preparation.² Per USP 795, CNSPs with an aw ≥ 0.6 and a BUD within the limits of Table 7 should contain appropriate antimicrobial agents to protect against the growth of bacteria, yeast, and mold that may be inadvertently introduced anytime during the compounding process or throughout the BUD under appropriate handling and storage conditions.² In choosing a preservative, consideration should be given to its effectiveness in preventing microbial growth and maintaining the stability of the preparation.² When antimicrobial preservatives are contraindicated in a CNSP, storage of the preparation in a refrigerator is required if such storage does not change the physical or chemical properties of the CNSP (i.e., precipitation).²

Table 6

Water Activity of Common Compounded Nonsterile Dosage Forms²

Nonaqueous Dosage Forms: a_w < 0.6			Aqueous Dosage Forms: a_w ≥ 0.6
Dosage Form	Description	a_w	Dosage Form	Description	a_w
Animal treat	Animal treat (oil flavor)	0.507	Animal treat	Animal treat with 15%–18% aqueous flavor	0.716
Capsule (oil-filled)	Olive oil encapsulated	0.468	Cream	Cream vehicle (oil in water emulsion, petrolatum-free)	0.968
Capsule (powder-filled)	Powder-based encapsulated	0.435	Cream	Emollient cream (petrolatum and mineral oil)	0.984
Gel (glycol-based)	Propylene glycol, ethoxy diglycol, hydroxypropyl cellulose gel	0.056	Cream	Cream (oil-in-water emulsion with natural oils)	0.989
Lollipop (sorbitol-based)	Sorbitol-based lollipop	0.460	Foam	Foaming surfactant solution	0.983
Ointment	Hydrophilic petrolatum	0.396	Gel (water- based)	Alcohol-free aqueous gel	0.990
Ointment	Polyethylene and mineral oil gel base	0.459	Gel (water- based)	Hydroxypropyl methylcellulose (HPMC) gel	1.000
Oral solution (glycol-based)	20% Polyethylene glycol and 80% propylene glycol	0.009	Lotion	Lotion (oil-in-water emulsion)	0.986
Oral solution (oil-based)	Medium-chain triglyceride oil	0.338	Nasal spray	Nasal spray	0.991
Oral suspension (fixed oil)	Fixed oil with thickener	0.403	Oral solution (water- based)	Low-sucrose syrup vehicle	0.906
Powder for inhalation	Encapsulated powder for inhalation	0.402	Oral solution (water- based)	90% Water and 10% glycerin	0.958
Stick	Lip balm	0.181	Oral suspension (water- based)	Oral suspension base	0.992
Suppository	Polyethylene glycol base	0.374	Rinse	Polymer gel with 30% water	0.960
Suppository	Fatty acid base	0.385	Shampoo	Shampoo	0.976
Tablet (compressed)	Compressed tablet	0.465	Simple syrup	Simple syrup	0.831
Tablet (triturate)	Tablet triturate (lactose and/or sucrose)	0.427	—	—	—
Troche or lozenge (gelatin-based)	Gelatin troche or lozenge with NMT 3% aqueous flavor	0.332	—	—	—
Troche or lozenge (glycol-based)	Polyethylene glycol troche or lozenge with NMT 3% aqueous flavor	0.571	—	—	—

Table 7

BUD Recommendations²

Type of preparation	BUD	Storage Temp
Aqueous dosage forms with water activity ≥ 0.60
Non-preserved aqueous dosage form	14	Refrigerator
Preserved aqueous dosage form	35	CRT or refrigerator
Nonaqueous dosage forms with water activity <0.60
Oral liquids (nonaqueous)	90	CRT or refrigerator
Other nonaqueous dosage forms	180	CRT or refrigerator

The ultimate responsibility for assigning beyond-use dates rests with compounding personnel, under the oversight of the designated person or persons.² The concept of a designated person is new within the revised guidelines. Their institution deems these individuals responsible and must use professional judgment when determining beyond-use dates.² Ideally, each institution should utilize a standardized, guideline-driven approach and have established policies and procedures for assigning beyond-use dates. BUD recommendations within USP <795> assume the product is packaged in a light-resistant, tight container (unless other conditions apply).² The maximum beyond-use date that can be assigned to any nonsterile preparation is 180 days.²

The Role of the Pharmacy Technician

In the pharmacy setting, compounding can improve patient outcomes by promoting medication adherence.⁶ Nonsterile compounding is a specialized skill for pharmacy technicians. They can assist in preparing safe, high-quality, and effective compounds by utilizing skills in weighing, mixing, and measuring, as well as techniques specific to each dosage form. Pharmacy technicians can also assist pharmacists in determining if a patient has experienced any issues with their compounded medications. Useful resources pertaining to the topic include the Art, Science, and Technology of Pharmaceutical Compounding, The International Journal of Pharmaceutical Compounding, and USP <795> - Pharmaceutical Compounding - Nonsterile Preparations.

Summary

Nonsterile compounding involves preparing a wide range of dosage forms, each requiring specific techniques to ensure safety, quality, and effectiveness. Compounding personnel, including pharmacists and pharmacy technicians, should be skilled in preparing various dosage forms to produce safe, high-quality, and effective medications. This includes skills related to particle size reduction, mixing, and weighing. Personnel should be competent in preparing tablets, capsules, solutions, suspensions, and lozenges and assigning appropriate beyond-use dates.

References

Allen, Lloyd. The Art, Science, and Technology of Pharmaceutical Compounding, 6th Edition. APhA. October 2020.

General Chapter: USP. Pharmaceutical Compounding - Nonsterile Preparations <795>. In: USP–NF. Rockville, MD: USP; 2023.

Gullapalli RP, Mazzitelli CL. Gelatin and Non-Gelatin Capsule Dosage Forms. J Pharm Sci. 2017;106(6):1453-1465. doi:10.1016/j.xphs.2017.02.006

Thompson J. A practical guide to contemporary pharmacy practice. 2^nd Edition. Lippincott Williams and Wilkins. 2004.

Capsules. Pharmaceutics and Pharmaceutical Compounding Laboratory. https://pharmlabs.unc.edu/labexercises/compounding/capsules. Accessed March 2026.

Carvalho M, Almeida IF. The Role of Pharmaceutical Compounding in Promoting Medication Adherence. Pharmaceuticals (Basel). 2022;15(9):1091. Published 2022 Aug 31. doi:10.3390/ph15091091

DISCLAIMER

The information provided in this course is general in nature, and it is designed solely to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.

Healthcare professionals must consult their employer, healthcare facility, hospital, or other organization for guidelines, protocols, and procedures to follow. The information provided in this course does not replace those guidelines, protocols, and procedures, but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.

Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses is constantly changing. Any person taking this course understands that such a person must make an independent review of medication information before any patient assessment, diagnosis, treatment and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.

Nothing contained in this course represents the opinions, views, judgments, or conclusions of RxCe.com LLC. RxCe.com LLC is not liable or responsible to any person for any inaccuracy, error, or omission with respect to this course or course material.

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