Study On Preparation Technology Optimization Of Two Kind Of Water-Soluble Freeze-drying Preparations

The freeze-drying processes of water-soluble amifostine and cinepaizde maleate are studied and optimited in this paper.The technological process of amifostine is studied by orthogonal test,the manufacturing parameters of amifostine freeze-drying process include different additives,additive ratioes additive is M,the M ratio is 10%,the the pre-freezing temperature is -25℃,the annealing time is 3 hours,the annealing times are 3 times,the sublimation time is 36 hours,the desorption time is 2 hours,According to the optimal freeze-drying process,the quality of water in the amifostine crystalline preparation is between 19%and 22%,the relative standard deviation of moisture content which is in the same process is 1.6%.The temperature accelerating experiment of amifostine crystalline preparation is studied for 27days,57days,72days and 87days at 40℃.,the quality index all accord with USP31(2008).Through BP neural network technology based on experimental datas,the nonlinear function of seven freeze-drying parameters and the quality of water in the preparation is fitted; finally,the freeze-drying process of amifostine is optimized using genetic algorithm.The optimal results are that additive ratio is 10.2%(v/v),the pre-freezing temperature is -25.1℃, the sublimation time is 38.2 hours,the desorption time is 2.0 hours,the annealing time is 2.1 hours,the annealing times are 3 times.The total freeze-drying time is 56.6 hours,and it is saved about 5.6%,comparing to the experimental total time which is 60hours,this freeze-drying process is verified by the experiment.The freeze-drying optimal process of cinepazide maleate preparation is that the additive is mannitol,the quality of mannitol is 160mg/ml,the pre-freezeing temperature is -35℃,the pre-freezing maintaining time is 3 hours,the sublimation time is 10 hours,the sublimation temperature is -16℃,the desorption time is 9 hours,the desorption temperature are -5℃, 20℃,40℃.The appearance of cinepazide maleate preparation is plump,the moisture content in the preparation is less than 1.0%.According to this process,the quality of cinepazide maleate is more than 99.0%and the quality of related substance is less than 0.2%,the results accord with State Food and Drug Administration:WS-069-(X-060)-2002.Comparing to cinepazide maleate solution,it is affected lightly by ultraviolet ray.