Effect of Production Process on the Clarity of Ozagrel Sodium for Injection
Objective To investigate the critical process parameters affecting the clarity of Ozagrel Sodium for Injection.Methods By designing and implementing a full factorial design of experiment(DOE),the significance levels of the effects of five factors(including the pre-freezing rate,batching temperature,pH,type of rubber stopper and vacuum conditions in the vial)on the clarity of Ozagrel Sodium for Injection were analyzed.The effect of rubber stopper prescription on the clarity was analyzed through the single factor experiment to find the optimal alternative rubber stopper.Results The main factors affecting the clarity were the type of rubber stopper and vacuum conditions in the vial,and there was an interaction between the two factors.The optimal process parameters obtained by fitting were as follows:the solution temperature was 25 ℃,the pH value of drug liquid was 9.0±0.1,the chlorinated butyl rubber stopper was used,and nitrogen gas was maintained in the vial,the pre-freezing rate was selected as fast freezing,and the sublimation drying process remained unchanged.Three batches of samples were prepared by this process,and it was verified that products with qualified clarity could be obtained.Conclusion The type of rubber stopper and the vacuum conditions in the vial are critical control conditions for the industrial-scale production of Ozagrel Sodium for Injection.The potential components in the rubber stopper can affect the clarity of the product.The optimized process parameters can realize the industrial-scale production and ensure the quality of products.
Ozagrel Sodium for Injectionclarityproduction processfull factorial design of experiment
万方数据
维普
