注射用还原型谷胱甘肽冻干工艺的优化

Optimization of Freeze-drying Process of Reduced Glutathione for Injection

为提高注射用还原型谷胱甘肽的稳定性及缩短冻干周期,以冻干时间、产品外观、水分等关键质量属性为指标,对溶剂和干燥温度进行了单因素优化。最终确定采用1%叔丁醇的水溶液作溶剂溶解谷胱甘肽和碳酸氢钠,预冻时隔板温度为–50℃,维持3 h至药物全部冻实,再控制一次干燥温度为–36℃,真空度为20 Pa,维持21 h待溶剂完全升华,继续维持2 h,最后控制隔板温度为50℃,真空度在10 Pa以下,维持4 h,完成二次干燥。所得冻干品外观为白色块状,水分和残留溶剂均较低。且经初步稳定性试验,各质量属性没有发生变化,样品稳定性较好,且冻干周期明显缩短。

In order to improve the stability of reduced glutathione for injection and shorten the freeze-drying cycle,single factor test was carried out to select the solvent and drying temperature of freeze-drying process with several key quality attributes such as freeze-drying time,product appearance and moisture as indicators.The optimal conditions were as follows.First,glutathione and sodium bicarbonate were dissolved in 1%tert-butanol aqueous solution.Next,the solution was pre-frozen at–50℃for 3 h until the drug was completely frozen.Then,the drying temperature of primary drying was adjusted to–36℃and the vacuum degree was kept at 20 Pa for 21 h until the solvent was completely sublimated.After maintaining for 2 h,the temperature of second drying was adjusted to 50℃and the vacuum degree was kept below 10 Pa for 4 h.The obtained freeze-dried product had a white appearance with low moisture and residual solvents.The results of preliminary stability test suggested that the sample had good stability with quality attributes remaining constant.Moreover,the freeze-drying cycle was significantly shortened.