Stability of Ribavirin for Inhalation Packaged in Syringes or Glass Vials when Stored Frozen, Refrigerated, and at Room Temperature.

The primary aim of this study was to investigate ribavirin solution for inhalation stability under three different conditions (frozen, refrigerated, room temperature) over a 45-day period. A ribavirin 6000-mg vial was reconstituted with 90 mL of Sterile Water for Injection per the package insert to yield a concentration of approximately 67 mg/mL. The solution was then placed in either syringes or empty glass vials and stored in the freezer (-20°C), in the refrigerator (~0°C to 4°C), or at room temperature (~20°C to 25°C). Original concentrations were measured on day 0 and subsequent concentrations were measured on day 2, 14, and 45 utilizing a validated liquid chromatography with tandem mass spectrometry assay. All analyses were performed in triplicate for each storage condition. Additionally, at each time point the physical stability was evaluated and the pH of solution was measured. The solution was considered stable if =90% of the original concentration was retained over the study period. A validated liquid chromatography with tandem mass spectrometry analysis demonstrated that >95% of the original ribavirin concentration was preserved over the 45-day period for all study conditions. The ribavirin concentration remained within the United States Pharmacopeia (USP)-required range of 95% to 105% of the original labeled product amount throughout the entire study period for all study conditions. Precipitation of ribavirin was noted during the thawing cycle for frozen samples, but the drug went back into solution once the thawing process was completed. No changes in color or turbidity were observed in any of the prepared solutions. Values for pH remained stable over the study period and ranged from 4.1 to 5.3. Ribavirin for inhalation solution is physically and chemically stable for at least 45 days when frozen, refrigerated, or kept at room temperature after reconstitution to a concentration of approximately 67 mg/mL and placed in syringes or glass vials.