国产艾司唑仑原料药及其片剂关键质量属性研究进展  

Research Progress on Critical Quality Attribute of Estazolam Active Pharmaceutical Ingredients and Estazolam Tablets

作　　者：沈丹丹 胡振晶 曾令高 唐华 SHEN Dandan;HU Zhenjing;ZENG Linggao;TANG Hua(Chongqing Institute for Food and Drug Control·NMPA Key Laboratory for Quality Monitoring of Narcotic Drugs and Psychotropic Substances,Chongqing,China 401121;Bioengineering College of Chongqing University,Chongqing,China 400044)

机构地区：[1]重庆市食品药品检验检测研究院·国家药品监督管理局麻醉精神药品质量监测重点实验室,重庆401121 [2]重庆大学生物工程学院,重庆400044

出　　处：《中国药业》2024年第3期19-25,共7页China Pharmaceuticals

基　　金：重庆市技术创新与应用发展专项资助项目[CSTB2022TIAD-GPX0071]。

摘　　要：目的为艾司唑仑片一致性评价质量研究提供参考。方法检索国产艾司唑仑原料药及其片剂关键质量属性的最新研究进展,结合生产工艺特点,基于风险评估确定关键质量属性指标,比较艾司唑仑原料药及其片剂国内外质量标准中关键质量属性指标控制差异,总结现行质量标准中可能存在的风险。结果艾司唑仑原料药现行标准2020年版《中国药典(二部)》(ChP2020)有关物质项下缺失特定杂质控制,同时原料药生产企业缺失基因毒性杂质研究与控制策略。艾司唑仑片现行标准ChP2020溶出条件区分力弱,溶出量、含量均匀度及含量测定紫外光谱法准确性差,有关物质控制策略不合理,不能反映国产艾司唑仑片的真实质量差异;一致性评价后,注册质量标准明显提升,主要是有关物质色谱条件及已知杂质限度差异较大。结论建议未通过一致性评价的生产企业开展艾司唑仑质量研究时,重点关注有关物质、杂质谱、基因毒性杂质、溶出度、含量均匀度、含量测定等关键质量属性指标,优化产品处方及工艺设计,以提高产品质量。建议修订ChP2020艾司唑仑原料药及其片剂的质量标准,以满足已上市药品质量监管的需求,保障用药的安全性和有效性。Objective To provide a reference for the quality research of consistency evaluation of Eszolam Tablets.Methods The latest research progress on the critical quality attribute(CQA)of domestic estazolam active pharmaceutical ingredients(API)and Estazolam Tablets was searched.Based on the characteristics of the production process and risk assessment,the CQA indicators were determined,the control differences of CQA indicators in the domestic and foreign quality standards of estazolam API and Estazolam Tablets were compared,and the possible risks in the current quality standards were summarized.Results The current standard of eszolam API in the related substance items in the Chinese Pharmacopoeia(Edition 2020)lacked specific impurity control,and the production enterprises of eszolam API lacked research and control strategies for genotoxic impurities.The current standard of Estazolam Tablets in the Chinese Pharmacopoeia(Edition 2020)had weak distinguishability in dissolution conditions,and poor accuracy of UV method for dissolution amount,content uniformity,and content determination.The control strategy for impurities related to substances was unreasonable and could not reflect the actual quality differences of domestic Estazolam Tablets.After consistency evaluation,the registration quality standards significantly improved,mainly including chromatographic conditions of the related substances and significant differences in known impurity limits.Conclusion It is recommended that production enterprises that have not passed the consistency evaluation should focus on CQA indicators such as substances,impurity spectra,genotoxic impurities,dissolution rate,content uniformity,and content determination when conducting quality research on estazolam,and continuously improve the quality of products by optimizing product formulation and process design.Meanwhile,it is recommended to revise the quality standards for estazolam API and Estazolam Tablets in the Chinese Pharmacopoeia(Edition 2020)to meet the quality supervision requiremen

关 键 词：艾司唑仑 关键质量属性 质量标准 风险评估 

分 类 号：R917[医药卫生—药物分析学] R971.3[医药卫生—药学]