Stability Study of Meropenem 50 mg/mL Eye Drops in Polypropylene Dropper Bottles

Background/Objectives: Meropenem is a broad-spectrum carbapenem antibiotic with demonstrated efficacy against multidrug-resistant Gram-negative pathogens. Although its use as an ophthalmic formulation is off-label, growing clinical evidence supports its application in severe ocular infections such as keratitis and endophthalmitis. However, the intrinsic instability of meropenem in aqueous solutions and the absence of standardized ophthalmic preparations limit its routine use. Furthermore, no stability studies are currently available for meropenem 50 mg/mL eye drops stored in polypropylene (PP) dropper bottles under freezing and subsequent refrigerated conditions. The aim of this study was to evaluate the physicochemical and microbiological stability of a 50 mg/mL meropenem ophthalmic solution prepared in a hospital pharmacy using a commercial meropenem pharmaceutical product, and packaged in PP containers. Methods: Eye drops were aseptically prepared from a commercially available pharmaceutical product, containing 1g de meropenem and anhydrous sodium carbonate as an excipient. After preparation, the drops were stored at -20 ± 2 °C for up to 42 days, followed by refrigerated storage (5 ± 3 °C) after thawing for up to 7 days. Chemical stability was assessed using a validated stability-indicating HPLC method in accordance with ICH guidelines and was defined as 90-110% recovery of the initial concentration. Physical stability (appearance, pH, particulate matter) and microbiological stability were also evaluated under simulated in-use conditions. Results: The HPLC method demonstrated excellent linearity, precision, and accuracy. Meropenem concentrations remained within the predefined acceptance limits throughout the 42-day study period under freezing conditions, with no significant changes in pH, color, or particulate formation. After thawing, a progressive decrease in drug concentration was observed under refrigerated conditions, falling below 90% of the initial concentration within 24-48 h. A concomitant color change from colorless to yellow was also detected, consistent with β-lactam ring hydrolysis. Despite this degradation, no significant changes in physical parameters other than color were observed, and microbiological testing confirmed sterility for up to 7 days under refrigerated conditions. Conclusions: Meropenem drops 50 mg/mL in PP dropper bottles are physicochemically and microbiologically stable for 43 days (42 days under frozen conditions plus 1 day, in-use conditions, after opening and under refrigeration).