Larson Bayli, Bushman Lane R, Casciano Matthew L, Oldland Alan R, Kiser Jennifer J, Kiser Tyree H
University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado.
University of Colorado Hospital, Aurora, Colorado.
Int J Pharm Compd. 2016 Nov-Dec;20(6):521-525.
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.
本研究的主要目的是在45天的时间内，研究利巴韦林吸入溶液在三种不同条件（冷冻、冷藏、室温）下的稳定性。按照包装说明书，用90 mL注射用水将一支6000 mg的利巴韦林小瓶复溶，配制成浓度约为67 mg/mL的溶液。然后将该溶液置于注射器或空玻璃小瓶中，分别储存在冷冻箱（-20°C）、冰箱（约0°C至4°C）或室温（约20°C至25°C）下。在第0天测量初始浓度，随后在第2天、第14天和第45天，使用经过验证的液相色谱-串联质谱分析法测量浓度。每种储存条件下的所有分析均重复进行三次。此外，在每个时间点评估物理稳定性并测量溶液的pH值。如果在研究期间保留了≥90%的初始浓度，则认为该溶液稳定。经过验证的液相色谱-串联质谱分析表明，在所有研究条件下，45天内利巴韦林的初始浓度保留率均＞95%。在整个研究期间，所有研究条件下利巴韦林的浓度均保持在美国药典（USP）要求的初始标示量的95%至105%范围内。冷冻样品在解冻过程中出现了利巴韦林沉淀，但解冻过程完成后药物又重新溶解。在任何制备的溶液中均未观察到颜色或浊度的变化。在研究期间pH值保持稳定，范围为4.1至5.3。利巴韦林吸入溶液复溶至浓度约为67 mg/mL并置于注射器或玻璃小瓶中后，在冷冻、冷藏或室温保存时，在物理和化学性质上至少45天是稳定的。
