Study And Optimization On Manufacturing Process Of Freeze Drying Preparation Of Crystal Amifostine

Amifostine is the first broad-spectrum cell medicament which is accepted in the world.It can keep effectively normal tissues off the damage from radioactive and chemical treatment, and is applied extensively in the clinic.It is full of practical and academic meaning to study on this topic.First,amifostine solution concentration,additive and additive ratio are studied in the orthogonal experiment of stable crystal amifostine preparation,which is produced by vacuum freeze drying.According to their important effect on amifostine solution,their order is: amifostine solution concentration,additive,additive ratio.The optimized experiment value for amifostine is 80mg/ml-100mg/ml,the additive is acetone or ethanol,the additive ratio value is between 8%-10%and the freeze drying solution for amifostine doesn't contain any excipient.Second,the freeze drying process is studied through vacuum freeze drying experiment.According to factors' important effect on freeze drying process of amifostine, their order is:second drying time,prefreeze maintaining time,prefreeze final plate point,and sublimation time.The optimized values for second drying time,prefreeze maintaining time, prefreeze final plate point and sublimation time separately are:3.7hours,2.5hours,-25℃and 22.3hours.The total time for vacuum freeze drying is 31 hours.Third,the accelerating stability experiment of amifostine preparation produced under the optimized process parameters using freeze drying is studied.Through five month's acceleration experiment,the amifostine is detected using high pressure liquid chromatography and the datum show stability.Using neural network,these datum are regressed and the nonlinear function for these parameters in the freeze drying process for amifostine is got.The experiential mathematic model for freeze drying process of crystal amifostine is also got.Based on this function,the total freeze drying time for crystal amifostine is optimized using genetic algorithm.The optimized results are:additive is acetone,additive ratio is 8.4%,amifostine solution concentration is 80mg/ml,prefreeze final plate point is -25℃,prefreeze maintaining time is 2.5hour,sublimation time is 22.3hour,second drying time is 3.5hour.The total optimized freeze drying time is 29.5 hour,and it is saved about 4.8%comparing with the experiment results of 31 hours.