Stability study including impact of temperature excursions on a new vancomycin eye drop formulation

OBJECTIVES: Severe bacterial keratitis is likely to require treatment with highly concentrated antibiotic eye drops. Such concentrated eye drops are not marketed, and so hospital pharmacies are required to compound and store them. The aim of the present study was to develop a new fortified 50 mg/mL vancomycin eye drop containing a preservative and to study its physicochemical, microbiological stability and preservative efficacy when stored in adapted conditions and with transient temperature excursions. METHODS: Vancomycin concentration was controlled using high-performance liquid chromatography with an ultraviolet detector stability-indicating method, developed and validated in accordance with International Conference on Harmonization guidelines. Limpidity, non-visible particles, pH and osmolality controls were performed. Eye drop sterility and efficacy of antimicrobial preservation with different bacterial strains were also tested. Different temperature excursion times (from 0.5 to 12 hours) were tested. RESULTS: After 3 months of freezing at -20°C followed by 7 days storage at temperature between 2°C and 8°C, vancomycin concentration, visible and non-visible particles, osmolality and pH remained in accordance with the initial specifications. No degradation products appeared. After a transient temperature excursion from -20°C to 25°C for a maximum of 12 hours, the eye drops remained stable for 7 days between 2°C and 8°C. No microbial contamination occurred when the drops were used daily for 7 days (mimicking patient conditions). CONCLUSIONS: The new vancomycin eye drop formulation remains stable even in cases of temperature excursion.