Quality Control of a Compounded Cream: Beyond-Use Date and Preservation
A hospital pharmacy prepares a 1% hydrocortisone cream in a proprietary base for a dermatology ward. The pharmacy prepares a 500 g batch every month and dispenses in 100 g jars. The pharmacist must assign a beyond-use date (BUD). The cream contains no added preservative; the base is an oil-in-water emulsion with water activity sufficient to support microbial growth. The pharmacy has no stability chamber but follows USP <795> guidelines. The pharmacist considers assigning a BUD of 30 days at room temperature (25°C) or 90 days refrigerated (2–8°C). The cream is used for patients with intact skin but some have minor excoriations.
1. Using USP <795> principles, determine the appropriate BUD for this compounded cream, justifying your choice based on the preparation type, preservative status, and intended use. Discuss whether refrigeration extends the BUD.
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USP <795> classification:
This is a nonsterile compounded preparation that is water-containing and preservative-free. According to USP <795>, for nonpreserved aqueous preparations, the default BUD is 14 days when stored refrigerated (2–8°C) or 7 days at controlled room temperature (20–25°C). However, the pharmacist may extend the BUD if there is a stability-indicating assay or published stability data for the specific formulation.
Application to this cream:
- The cream is an O/W emulsion with water, no preservative, and intended for use on intact or slightly broken skin. Microbial contamination risk is significant.
- Without preservative, the BUD should not exceed 14 days refrigerated. A 30-day room temperature BUD is not justified.
- Refrigeration (2–8°C) can extend BUD to 14 days, but not 90 days, because microbial growth may still occur slowly, and emulsion stability may be compromised (e.g., phase separation).
- The pharmacist should consider adding a preservative (e.g., propylparaben) if the base allows, which could extend BUD to 30 days refrigerated per USP <795> for preserved aqueous preparations.
Conclusion: Assign a BUD of 14 days refrigerated (or 7 days at room temperature) unless stability data support longer. Label with 'Refrigerate' and 'Shake well' if applicable. Discard if separation or discoloration occurs.
2. Describe two quality control tests the pharmacy should perform on each batch before dispensing, and explain how these tests address the risks associated with this cream.
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1. Visual inspection for phase separation and homogeneity:
- Test: Observe the cream for uniform appearance, no visible oil or water separation, no grittiness.
- Risk addressed: Physical instability of the emulsion can lead to inconsistent drug distribution and reduced efficacy. It also indicates potential microbial contamination if separation occurs.
- Method: Take a small sample from top, middle, and bottom of the batch; spread on a glass slide and examine for uniformity.
2. Microbial limit testing (if resources allow) or preservative efficacy test:
- Test: Since the cream is preservative-free, perform a bioburden check (e.g., total aerobic microbial count) on a sample from each batch. Alternatively, ensure the base and equipment are sterile or sanitized.
- Risk addressed: Microbial contamination can cause skin infections, especially in patients with excoriations.
- Method: If no microbiology lab, use a simple test: inoculate a sample on tryptic soy agar and incubate at 30–35°C for 48–72 h; compare with negative control.
Additional test: Check pH (if applicable) to ensure compatibility with hydrocortisone stability (pH 4–6).
Documentation: Record results in batch record; reject if out of specification.