正交设计法优化注射用福奈妥匹坦帕洛诺司琼工艺

Preparation Process Optimization of Fosnetupitant and Palonosetron for Injection by Orthogonal Test

目的:采用冷冻干燥法制备注射用福奈妥匹坦帕洛诺司琼,正交设计法对制备工艺进行优化。方法:以有关物质1(福奈妥匹坦有关物质)、有关物质2(帕洛诺司琼有关物质)、综合评分(有关物质1权重为3分,有关物质2权重为7分)为评价指标,采用单因素考察福奈妥匹坦氯盐酸盐溶解温度、福奈妥匹坦氯盐酸盐溶解pH、中间体药液pH和光照强度对有关物质的影响;根据单因素试验结果,采用L_(9)(3^(4))正交试验法对各因素进行进一步优化,并对优化工艺进行验证。结果:优化后的制备工艺:福奈妥匹坦氯盐酸盐溶解温度为30℃,福奈妥匹坦氯盐酸盐溶解pH为12.0,中间体药液pH为8.3;样品制备过程全程密封。优化后的工艺所得成品的有关物质1为0.61%,有关物质2为0.41%。结论:优化后的注射用福奈妥匹坦帕洛诺司琼工艺具有很好的可行性、可控性及耐用性,且稳定性好。

Objective:To prepare fosnetupitant and palonosetron for injection by a freeze-drying method and optimize the preparation process by orthogonal test.Methods:Taking the related substance 1(fosnetupitnt related substances),related substance 2(palonosetron related substances)and the comprehensive score(the weight value of related substance 1 was 3 points,and that of related substance 2 was 7 points)as the evaluation indicators,a single factor test was used to investigate the effects of fosnetupitant chloride hydrochloride dissolution temperature,fosnetupitant chloride hydrochloride dissolution pH value,intermediate liquid pH value,and strength of illumination on the related substances.L_(9)(3^(4))orthogonal test method was used to further optimize fosnetupitant chloride hydrochloride dissolution temperature,fosnetupitant chloride hydrochloride dissolution pH value,and intermediate liquid pH value,and the optimization process was verified.Results:The optimized preparation process of fosnetupitant and palonosetron for injection was confirmed as follows:the fosnetupitant chloride hydrochloride dissolution temperature was 30℃,the fosnetupitant chloride hydrochloride dissolution pH value was 12.0,and the intermediate liquid pH value was 8.3.The whole process of sample preparation was sealed.The related substance 1 in the finished product obtained from the optimized process was 0.61%,and the related substance 2 was 0.41%.Conclusion:The optimized process of fosnetupitant and palonosetron for injection is feasible,controllable and durable with good stability.