Analysis of the Stability of Compounded Vancomycin Hydrochloride Oral Solution: A Comparison Between Formulations Prepared Using a Commercial Product and Using the Pure Active Ingredient

TL;DR

This study compares the stability of compounded vancomycin oral solutions made from pure drug and a commercial product, finding that refrigeration extends their shelf life to 90 days.

Contribution

The study provides new stability data for compounded vancomycin solutions under different storage conditions and formulations.

Findings

Both formulations remained microbiologically stable for 90 days under refrigeration.

The API formulation lost potency faster at room temperature compared to the commercial product.

Buffering with citric acid helped maintain pH and prevent precipitation in the API formulation.

Abstract

Background

Oral vancomycin is the mainstay treatment for Clostridioides difficile infections. Compounded oral solutions are commonly prescribed, but their beyond-use date (BUD) is restricted to 14 days. Extending this limit would enhance patient convenience and pharmacy efficiency. Stability may depend on storage conditions and whether the formulation is prepared from pure active pharmaceutical ingredient (API) or a commercial injectable product.

Aim

To evaluate and compare the physicochemical and microbiological stability of compounded vancomycin hydrochloride oral solutions prepared from pure API and a commercial injectable product.

Methods

Two 12.5 mg/mL vancomycin hydrochloride formulations in United States Pharmacopeia (USP) Simple Syrup were prepared: one from Vitalis® injectable powder and one from pure API buffered with citric acid. Solutions were stored in high-density polyethylene (HDPE) bottles at room temperature (20°C) or refrigerated (2-8°C) for 90 days. Stability was assessed by high-performance liquid chromatography (HPLC), pH monitoring, and microbial testing according to USP <61> (microbial enumeration) and USP <62> (tests for specified microorganisms).

Results

Both formulations remained microbiologically stable for 90 days, with microbial counts within USP limits and no Escherichia coli detected. At room temperature, the API formulation lost >10% potency after 60 days, while the commercial product remained above 90% potency but showed >10% degradation from its initial value, with precipitation occurring by day 90. Under refrigeration, both formulations maintained potency and physical stability throughout the 90-day period. Buffering with citric acid preserved pH within USP specifications, whereas the unbuffered commercial product exceeded acceptable limits over time.

Conclusion

Compounded vancomycin hydrochloride oral solutions are stable and microbiologically safe for up to 90 days under refrigeration, and for at least 30 days at room temperature. Buffering agents are recommended to prevent pH drift and precipitation. Extending the BUD supports more flexible dispensing, reduces patient burden, and optimizes pharmacy workflows while ensuring therapeutic efficacy and safety.

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