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

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.

Keywords: drug compounding; drug stability; formulation design; high-performance liquid chromatography (hplc); physicochemical properties.