Stability Study of a Frozen Oseltamivir 15 mg/mL Oral Solution in Amber Glass Bottles

Background/Objectives: Oseltamivir is a widely used antiviral agent indicated for the treatment of influenza and plays a central role in pandemic preparedness strategies. Although an extemporaneously prepared 15 mg/mL oral solution is recognized in formularies, preparing large volumes during a pandemic requires extended storage options. However, no stability studies are currently available for an oseltamivir 15 mg/mL oral solution stored under freezing and subsequent refrigerated conditions for the duration of a standard treatment. The aim of this study was to evaluate the physicochemical and microbiological stability of a 15 mg/mL oseltamivir oral solution prepared from the active pharmaceutical ingredient (API) and packaged in amber glass containers. Methods: The oral solution was formulated using oseltamivir phosphate API, sodium benzoate as a preservative, and purified water and then packaged in 125 mL Type II amber glass bottles, allowing for thermal expansion. The samples were stored at -20 ± 2 °C for up to 75 days, followed by refrigerated storage (5 ± 3 °C) after thawing for up to 10 days. Chemical stability was assessed using a validated HPLC method in accordance with ICH guidelines and was defined as 90-110% recovery of the initial concentration. Physical stability (color, pH, particulate matter, crystallization, and homogeneity) and microbiological stability were also evaluated. Results: The HPLC method demonstrated excellent linearity, precision, and accuracy. Oseltamivir concentrations remained within the predefined acceptance limits throughout the 75-day study period under freezing conditions, with no significant changes in pH, color, or particulate formation. After thawing, the drug concentration continued to remain fully stable and within the required limits for up to 10 days under refrigerated conditions. Despite the prolonged storage and phase changes, no significant changes in physical parameters were observed, and microbiological testing confirmed the absence of aerobic, anaerobic, and fungal microorganisms on the final day of the study. Conclusions: Oseltamivir 15 mg/mL oral solution in amber glass bottles is physicochemically and microbiologically stable for up to 85 days (75 days under frozen conditions plus 10 days under refrigeration after thawing).