中国药物警戒 ›› 2022, Vol. 19 ›› Issue (7): 702-707.
DOI: 10.19803/j.1672-8629.2022.07.02

• 机制性模型在药物研发和评价中的应用专栏（一） • 上一篇    下一篇

兰索拉唑肠溶胶囊生物相关性溶出方法的构建研究

张锦琳1, 李岩1Δ, 陈涛2, 周颖1,3, 宋芸峰1,3, 贾欢欢1,4, 袁耀佐1,*, 曹玲1, 张玫1, 王晨5#, 许明哲5   

  1. 1江苏省食品药品监督检验研究院,国家药品监督管理局化学药品杂质谱研究重点实验室,江苏 南京210019;
    2上海凡默谷信息技术有限公司,上海200127;
    3南京中医药大学,江苏 南京210023;
    4中国药科大学,江苏 南京211121;
    5中国食品药品检定研究院,北京 102629
  • 收稿日期:2021-12-29 出版日期:2022-07-15 发布日期:2022-07-12
  • 通讯作者: *袁耀佐,男,博士,主任药师,药物仪器分析及其在质量评价中的应用。E-mail：yyzyz7256@sina.cn。#为共同通信作者。
  • 作者简介:张锦琳,女,硕士,副主任药师,现代药物分析技术及其在药物质量标准中的应用与仿制药一致性评价。Δ为并列第一作者。
  • 基金资助:
    重大新药创制国家科技重大专项2017年度（2017ZX09101001）; 江苏省市场监督管理局科技计划项目（KJ21125117）

Establishment of a bio-relevance dissolution method for lansoprazole enteric capsules

ZHANG Jinlin1, LI Yan1Δ, CHEN Tao2, ZHOU Ying1,3, SONG Yunfeng1,3, JIA Huanhuan1,4, YUAN Yaozuo1,*, CAO Ling1, ZHANG Mei1, WANG Chen5#, XU Mingzhe5   

  1. 1Jiangsu Institute for Food and Drug Control, NMPA Key Laboratory for Impurity Profile of Chemical Drugs, Nanjing Jiangsu 210019, China;
    2Pharmogo Co., Ltd., Shanghai 200127, China;
    3Nanjing University of Chinese Medicine, Nanjing Jiangsu 210023, China;
    4China Pharmaceutical University, Nanjing Jiangsu 211121, China;
    5National Institutes for Food and Drug Control, Beijing 102629, China
  • Received:2021-12-29 Online:2022-07-15 Published:2022-07-12

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摘要： 目的 探索建立兰索拉唑肠溶胶囊生物相关性溶出方法,为药品常规质量控制及市场监管提供有效手段。方法 根据前期研究所构建的兰索拉唑肠溶制剂的体内外相关性模型,结合体外溶出数据、肠溶胶囊的制剂处方以及体外溶出模型进一步开发生物相关的溶出条件。结果 推测可能的生物相关溶出方法：采用美国药典（the United States Pharmacopoe-ia, USP）篮法;设定仪器转速为150 r·min-1;45 min之前采用pH 5.8的磷酸盐缓冲液;45~90 min调整溶出介质的pH,形成pH为7.5的缓冲液;90 min之后调整溶出介质的pH至10.0。通过体外溶出实验进一步验证和确认了该方法,表明模型推测的溶出方法具有较好的准确性。结论 建立的生物相关溶出方法,真实反映仿制药的内在质量,为药物的质量控制及一致性评价提供一种简单、便捷的手段,为科学监管提供新的思路。

关键词: 兰索拉唑, 肠溶胶囊, 体内外相关性, 溶出模型, 生物相关性

Abstract: Objective To provide effective means for daily drug quality control and market supervision by establishing a bio-relevance dissolution method for lansoprazole enteric-soluble capsules. Methods According to the correlation model of lansoprazole enteric dissolved formulations constructed in previous studies, the biorelevant dissolution conditions was further developed by combining with in vitro dissolution data, formulations of enteric dissolved capsules, in vitro dissolution model and other information. Results The dissolution model was established successfully, and the possible biorelevant dissolution method was speculated: basket method using USP I method. Set the rotating speed of the instrument at 150 rpm; before 45 minutes, phosphate buffer with pH 5.8 was used. From 45 min to 90 min, the pH of the dissolved medium was adjusted to form a buffer with a pH of 7.5. After 90 minutes, the pH of the dissolution medium was adjusted to 10.0. The method was confirmed by in vitro dissolution experiments, which indicated that the dissolution method predicted by the model had good accuracy. Conclusion The biorelated dissolution method established in this study truly reflects the inherent quality of generic drugs, provides a simple and convenient means for drug quality control and consistency evaluation, and provides a new idea for scientific supervision.

Key words: lansoprazole, enteric capsule, in vivo - in vitro correlation, dissolution model, bio-relevance

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