王珊, 花亚冰, 高翔, 张慧, 刘楠, 高静, 郑爱萍. 注射用乳酸-羟基乙酸共聚物微球的体内外相关性研究进展J. 药学学报, 2021,56(1): 158-168. doi: 10.16438/j.0513-4870.2020-1151
引用本文: 王珊, 花亚冰, 高翔, 张慧, 刘楠, 高静, 郑爱萍. 注射用乳酸-羟基乙酸共聚物微球的体内外相关性研究进展J. 药学学报, 2021,56(1): 158-168. doi: 10.16438/j.0513-4870.2020-1151
WANG Shan, HUA Ya-bing, GAO Xiang, ZHANG Hui, LIU Nan, GAO Jing, ZHENG Ai-ping. Research progress of in vitro-in vivo correlation of injectable polylactide-polyglycolide microspheresJ. Acta Pharmaceutica Sinica, 2021,56(1): 158-168. doi: 10.16438/j.0513-4870.2020-1151
Citation: WANG Shan, HUA Ya-bing, GAO Xiang, ZHANG Hui, LIU Nan, GAO Jing, ZHENG Ai-ping. Research progress of in vitro-in vivo correlation of injectable polylactide-polyglycolide microspheresJ. Acta Pharmaceutica Sinica, 2021,56(1): 158-168. doi: 10.16438/j.0513-4870.2020-1151

注射用乳酸-羟基乙酸共聚物微球的体内外相关性研究进展

Research progress of in vitro-in vivo correlation of injectable polylactide-polyglycolide microspheres

  • 摘要: 注射用乳酸-羟基乙酸共聚物(polylactide-polyglycolide,PLGA)微球作为一种储库型释药系统,自1989年第1个产品Lupron depot获准在美国上市起,已成功用于多种疾病的治疗,具备在体内几天到几个月长时间释药的能力,可显著改善用药安全性,提升患者顺应性。体内外相关性(in vitro-in vivo correlation,IVIVC)研究给微球制剂的发展带来更多可能。IVIVC可以通过微球的体外释放行为阐述体内释药的动态信息,在表征微球性能的同时减轻各阶段的工作量,对药物的研发、生产变更和监督管理等具有指导或支持作用。本文将注射用PLGA微球的释放机制、体内外释放测定涉及的常用方法和理论进行归纳总结,重点讨论了IVIVC尤其是A级IVIVC在微球制剂领域的建立及应用,为进一步的微球体内外相关性研究提供参考。

     

    Abstract: As a depot drug delivery system, injectable polylactide-polyglycolide (PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation (IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

     

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