Non-Sterile Compounding Deep Dive
Non-sterile compounding involves the preparation of customized medications that do not require sterility, such as oral solutions, suspensions, capsules, creams, ointments, and suppositories. USP Chapter 795 provides the standards for non-sterile compounding. This topic is tested on the CPHT exam and is essential for technicians working in compounding pharmacies.
Why Compound Non-Sterile Preparations?
- The needed strength is not commercially available.
- The patient cannot take the commercially available dosage form (e.g., a child who cannot swallow tablets needs a liquid).
- The patient has an allergy to an inactive ingredient in the commercial product.
- A product has been discontinued by the manufacturer.
- A combination product is needed that is not commercially available.
- A veterinary medication is needed.
USP 795 Key Requirements
- Compounding must be performed by or under the direct supervision of a licensed pharmacist.
- A master formulation record and a compounding record must be maintained for each preparation.
- All ingredients must be obtained from FDA-registered or inspected suppliers.
- Equipment must be properly maintained and calibrated.
- Appropriate PPE must be worn.
- The compounding area must be clean, orderly, and separate from dispensing areas.
Documentation
Master Formulation Record (MFR)
The MFR is the "recipe" for the preparation. It includes:
- Name, strength, and dosage form of the preparation
- Complete list of ingredients with quantities
- Equipment needed
- Step-by-step compounding instructions
- Packaging and storage requirements
- Beyond-use date assignment
- Quality control procedures
- References or source of the formula
Compounding Record (CR)
The CR documents each individual batch or preparation. It includes:
- Name, strength, and dosage form
- Date and time of compounding
- Name or initials of the compounder and verifying pharmacist
- Lot numbers and expiration dates of all ingredients used
- Actual quantities weighed or measured
- Assigned lot number for the compounded preparation
- Assigned beyond-use date
- Results of quality control checks
Equipment and Supplies
| Equipment | Purpose |
|---|---|
| Class III (torsion) balance | Weighing ingredients (sensitivity: 6 mg; capacity: up to 120 g) |
| Electronic/analytical balance | More precise weighing for small quantities |
| Graduated cylinders | Measuring liquids (use the smallest size that holds the needed volume for best accuracy) |
| Mortar and pestle | Trituration and levigation |
| Ointment slab (pill tile) | Mixing ointments and creams |
| Spatulas | Mixing and transferring materials |
| Capsule-filling equipment | Manual capsule machines, capsule shells |
| Suppository molds | Forming suppositories |
| Beakers and flasks | Mixing solutions |
| Stirring rods and magnetic stirrers | Dissolving ingredients |
| pH meter or pH paper | Testing acidity or alkalinity |
Compounding Techniques
Trituration
Grinding a solid substance in a mortar with a pestle to reduce particle size. Used to create fine powders for capsules or to mix two powders together.
Levigation
Adding a small amount of liquid (levigating agent) to a powder and grinding with a pestle or spatula to reduce particle size and create a smooth paste. Common levigating agents include mineral oil and glycerin.
Geometric Dilution
A technique for mixing a small amount of active ingredient with a large amount of diluent. Steps:
- Place the smallest quantity ingredient (usually the drug) in the mortar.
- Add an approximately equal amount of diluent and mix thoroughly.
- Continue adding diluent in amounts equal to the mixture in the mortar, mixing thoroughly each time.
- Repeat until all diluent has been incorporated.
This ensures even distribution of the active ingredient throughout the mixture.
Spatulation
Mixing powders or semisolids on an ointment slab using a spatula. Suitable for mixing ingredients that do not require particle-size reduction.
Punch Method (Capsule Filling)
A method for filling capsules by hand:
- Calculate the amount of drug and filler needed per capsule.
- Mix drug and filler using geometric dilution.
- Spread the powder evenly on an ointment slab.
- Repeatedly "punch" the empty capsule body into the powder until it is filled to the desired weight.
- Replace the capsule cap.
- Weigh each capsule to verify uniformity.
Common Dosage Forms Compounded
| Dosage Form | Key Considerations |
|---|---|
| Solutions | Drug must be completely dissolved. Use appropriate solvent. Filter if necessary. |
| Suspensions | Drug particles are dispersed, not dissolved. Must include "Shake well" label. Use a suspending agent for uniform distribution. |
| Capsules | Weigh each capsule for uniformity. Use appropriate capsule size. |
| Creams | Oil-in-water or water-in-oil emulsions. Mix active ingredient into the base thoroughly. |
| Ointments | Semisolid preparations. Incorporate drug using levigation if needed. |
| Suppositories | May require a displacement factor calculation. Melt the base, pour into molds, allow to cool. |
| Troches / Lozenges | Dissolve or disperse drug in a flavored base. Allow to harden in molds. |
Quality Control
Every compounded preparation should undergo quality control checks:
- Visual inspection: Check for proper appearance, color, consistency, and absence of foreign matter.
- Weight variation: For capsules, weigh individual capsules to verify they are within acceptable range.
- pH testing: For solutions and suspensions where pH is critical.
- Volume check: Verify that liquids meet the prescribed volume.
- Organoleptic testing: Check smell, color, and texture for consistency with expectations.
Beyond-Use Dating (BUD) for Non-Sterile Compounds
USP 795 provides general guidance on assigning BUDs to non-sterile compounds when stability data from the specific formulation is not available. The BUD should be conservative and based on the type of preparation and storage conditions. Consult the current version of USP 795 for the specific default BUD guidelines, as these are subject to revision.
General principles:
- Aqueous preparations generally have shorter BUDs due to microbial growth risk.
- Non-aqueous preparations typically have longer BUDs.
- The BUD cannot exceed the earliest expiration date of any ingredient used.
- Stability data from published literature or the manufacturer can support longer BUDs.
- Preparations should include a "Shake well" label (for suspensions), storage instructions, and the assigned BUD.
Labeling Requirements
Every compounded preparation must be labeled with:
- Patient name (if for a specific patient)
- Drug name, strength, and dosage form
- Quantity
- Directions for use
- Beyond-use date
- Storage conditions
- Lot number (if applicable)
- Any special instructions (e.g., "Shake well," "For external use only," "Keep refrigerated")
Exam Tips
- Know the difference between trituration, levigation, spatulation, and geometric dilution.
- Understand the purpose of the master formulation record vs. the compounding record.
- A Class III balance has a sensitivity of 6 mg - know this for LWQ calculations.
- Geometric dilution is used when mixing a small quantity of drug with a large quantity of diluent.
- USP 795 = non-sterile compounding; USP 797 = sterile compounding.
- "Shake well" is required on all suspensions.