不同来源的克拉霉素缓释片工艺降解杂质差异成因分析  

Analysis of the causes of differences in some impurities of clarithromycin sustained-release tablets from different sources

作　　者：谢升谷 黄艳[2] 孙逍 钱建钦 陈悦 孙楠[2] 洪利娅 XIE Sheng-gu;HUANG Yan;SUN Xiao;QIAN Jian-qin;CHEN Yue;SUN Nan;HONG Li-ya(Zhejiang Institute for Food and Drug Control,National Medical Products Administration Key Laboratory for Core Technology of Generic Drug Evaluation,Hangzhou 310052,China;Zhejiang University of Technology,Hangzhou 310014,China)

机构地区：[1]浙江省食品药品检验研究院,国家药品监督管理局仿制药评价关键技术重点实验室,杭州310052 [2]浙江工业大学,杭州310014

出　　处：《药物分析杂志》2020年第11期2042-2047,共6页Chinese Journal of Pharmaceutical Analysis

基　　金：浙江省药品监督管理局科技计划项目(2021005)。

摘　　要：目的:考察比较了国内市场上不同生产企业克拉霉素缓释片的杂质含量,并对其差异进行成因分析,为更好地评价药品质量属性和指导药品研发提供部分参考。方法:采用欧洲药典(EP 8.0)克拉霉素原料药项下有关物质检查方法,分别考察多个不来同源的克拉霉素缓释片及其原料药的杂质含量,并同时分析其不同制剂处方工艺对降解杂质含量差异的影响。结果:综合分析杂质含量数据及处方工艺内容,结果表明不同来源的克拉霉素缓释片其杂质含量差异较大,多数杂质是由原料药引入的工艺杂质,部分杂质属于制剂工艺过程中产生的降解杂质(杂质Ⅰ)。对杂质Ⅰ进行来源分析,发现杂质Ⅰ主要由酸降解所引起,且由于不同的制剂工艺对其产生也有影响。结论:杂质Ⅰ产生的重要影响因素为制剂处方中的酸性辅料,不同的工艺参数对杂质Ⅰ含量也有一定的影响。生产企业需充分关注和评估酸性辅料对克拉霉素降解杂质的影响,从而优化处方工艺,提高药品质量。Objective:To investigate and compare the impurity content of clarithromycin sustained-release tablets from different manufacturers in the domestic market,and analyze the causes of the differences,so as to provide some references for better evaluation of drug quality attributes and guidance of drug research and development.Methods:The EP8.0 test method for related substance in the clarithromycin bulk drug was used to detect the content of the impurities in clarithromycin sustained-release tablets and clarithromycin bulk drug from different sources.The influence of different formulation prescriptions on degradation impurity content was analyzed at the same time.Results:Comprehensive analysis of impurity content data and prescription process showed that the impurty content of Clarithromycin sustained-release tablets from different sources varied greatly.Most of the impurities were process impurities introduced by bulk drug,and some were degradation impurities(impurityⅠ)from the preparation process.ImpurityⅠwas mainly caused by acid degradation,and also affected by different preparation processes.Conclusion:An important factor influencing the generation of impurityⅠis the acidic excipient in the formulation.In addition,different process parameters also have certain influence.Manufacturers should pay attention to and evaluate the influence of acidic excipient on degradation impurities in clarithromycin sustained-release tablets,so as to optimize the formulation process and improve the drug quality.

关 键 词：克拉霉素缓释片 有关物质 降解杂质 酸性辅料 工艺 质量评价 

分 类 号：R917[医药卫生—药物分析学]