盐酸舍曲林片与原研制剂溶出一致性及药典方法合理性的研究

Study on the Consistency of Dissolution and Rationality of Chinese Pharmacopoeia Method for Sertraline Hydrochloride Tablets

关键词:  盐酸舍曲林片  溶出度  溶出曲线  一致性  相似因子

Key words:  sertraline hydrochloride tablets  dissolution rate  dissolution curve  consistency  similarity factor(f2)

摘要:

目的 考察8厂家盐酸舍曲林片与原研制剂溶出行为的一致性，探讨中国药典方法的可行性。方法 分别以0.1 mol·L^-1盐酸（pH=1.2）、乙酸盐缓冲液（pH=4.5）、磷酸盐缓冲液（pH=6.8）和水为溶出介质，选用中国药典溶出度色谱条件考察溶出曲线，采用相似因子法评价8厂家产品在各介质中与原研制剂溶出行为的相似性。结果 8厂家的仿制药与原研制剂在不同介质中溶出曲线差异较大，说明各企业的处方工艺差异较大；在pH=4.5介质、75 r·min^-1条件下原研和各厂制剂溶出量在15 min内均>85%。结论 通过不同介质溶出曲线的比较和f₂的计算，仿制药与原研制剂存在较大差异，建议企业改进工艺。同时中国药典的溶出条件有待商榷，建议国家药典委员会参考国外药典标准，修改转速或限度。

Abstract:

OBJECTIVE To inspect the consistency of dissolution of sertraline hydrochloride tablets from 8 manufacturers with the original manufacturer, and probe into the rationality of Chinese Pharmacopoeia method. METHODS Evaluated the similarity of dissolution of sertraline hydrochloride tablets from 8 manufacturers and original manufacturer by the similarity factor(f₂) within 0.1 mol·L^-1 hydrochloride acid(pH=1.2), acetic acid-natrium aceticum buffer solution(pH=4.5), phosphate buffer solution(pH=6.8) and water as medium, respectively by the dissolution chromatographic condition from Chinese Pharmacopoeia. RESULTS The stripping curves of the 8 manufacturers tablets were not quite similar with that of the original manufacturer, and it showed that the prescription and production process of each manufacturer were different. The drug dissolution was more than 85% in the condition of pH=4.5 medium and 75 r·min^-1. CONCLUSION By comparing the dissolution curves of different media and calculating f₂, there is a big difference between generic drugs and original agents. It is suggested that enterprises improve the process. At the same time, the dissolution conditions of the Chinese Pharmacopoeia need to be discussed. It is suggested that the Pharmacopoeia Commission revise the speed or limit by referring to the standards of foreign pharmacopoeia.