Stability of frozen 1% voriconazole ophthalmic solution

Abstract

Purpose: The physicochemical stability of frozen 1% voriconazole ophthalmic solution was evaluated.

Methods: Multiple batches of voriconazole 10-mg/mL eye drops were aseptically prepared in a laminar-airflow cabinet. One batch was analyzed immediately after preparation, and the rest were stored at -20 °C and analyzed using high-performance liquid chromatography at 30, 60, and 90 days to test their physicochemical stability and sterility. All samples were analyzed in triplicate. Additional analyses were performed to determine the solution's in vitro activity once thawed. The sterility of the 1% voriconazole solution was evaluated using blood-agar media and thioglycollate broth. Samples were incubated for 14 days and checked daily for signs of growth. Stability was defined as the absence of particles, color variation, or changes in pH and a remaining antifungal concentration of 90-110% of the initial concentration.

Results: All solutions remained clear and colorless throughout the study, and no precipitation or turbidity was observed in any of the batches, regardless of solution temperature. The pH and osmolarity of all batches remained essentially unchanged during storage at -20 °C and after thawing. No significant differences in concentration were observed during the storage at -20 or 5 °C. The voriconazole concentration remained within 10% of the initial concentration during the 90-day period of storage at -20 °C. The percentage of recovery was also optimal after thawing.

Conclusion: Voriconazole 1% solution prepared for ophthalmic use was stable and retained antifungal activity when stored at -20 °C for 90 days. After thawing, this extemporaneously prepared formulation was stable at 5 °C for 14 days.