注射用尿促性素的冻干工艺优化

Optimization of lyophilization process of menotrophin for injection

在确定尿促性素溶液的玻璃化转变温度和崩解温度的基础上,对一次升华和二次升华的影响因素的显著性进行考察,并通过响应面模型、全因子实验和温度挑战实验,结合压力升测试结果,确认最佳冻干参数。优化后的冻干工艺参数:预冻阶段保温温度分别于-25和-40℃维持65和120 min。一次升华温度为-12.5℃维持70 min。二次升华温度分别于5、20和40℃维持300、110和220 min。新冻干工艺将整个冻干周期由原来的22 h缩短至18.5 h,并有效降低干燥失重,达到提高生产效率、改进产品质量、降低生产成本的目标。

On the basis of the determination of the glass transition temperature and disintegration temperature of menotrophin solution,the significance of the influencing factors of primary and secondary sublimation was investigated,and the optimal lyophilization parameters were confirmed by response surface model,full factor experiment and temperature challenge experiment in combination with the results of pressure rise test.The optimized process parameters for lyophilization were as follows:the temperature at pre-freezing stage was maintained at-20 and-40℃for 40 and 120 min,respectively,the primary sublimation temperature was maintained at-10℃for 90 min and the secondary sublimation temperatures were maintained at 10,20 and 40℃for 300,110 and 220 minutes,respectively.The new lyophilization process can shorten the whole lyophilization cycle from the original 22 h to 18.5 h,effectively reduce the drying weight loss and achieve the goal of improving production efficiency as well as stability of product quality and reducing manufacturing costs.