University of Connecticut, Department of Pharmaceutical Sciences, Storrs, CT 06269, United States.
University of Connecticut, Department of Pharmaceutical Sciences, Storrs, CT 06269, United States.
Adv Drug Deliv Rev. 2023 Jul;198:114857. doi: 10.1016/j.addr.2023.114857. Epub 2023 May 5.
Poly(lactic-co-glycolic acid) (PLGA) microspheres are a sustained-release drug delivery system with several successful commercial products used for the treatment of a variety of diseases. By utilizing PLGA polymers with different compositions, therapeutic agents can be released over durations varying from several weeks to several months. However, precise quality control of PLGA polymers and a fundamental understanding of all the factors associated with the performance of PLGA microsphere formulations remains challenging. This knowledge gap can hinder product development of both innovator and generic products. In this review, variability of the key release controlling excipient (PLGA), as well as advanced physicochemical characterization techniques for the PLGA polymer and PLGA microspheres are discussed. The relative merits and challenges of different in vitro release testing methods, in vivo pharmacokinetic studies, and in vitro-in vivo correlation development are also summarized. This review is intended to provide an in-depth understanding of long-acting microsphere products and consequently facilitate the development of these complex products.
聚（乳酸-共-乙醇酸）（PLGA）微球是一种缓释药物递送系统，具有多种成功的商业化产品，用于治疗多种疾病。通过使用具有不同组成的 PLGA 聚合物，可以将治疗剂释放长达数周至数月的时间。然而，PLGA 聚合物的精确质量控制以及对与 PLGA 微球制剂性能相关的所有因素的基本理解仍然具有挑战性。这种知识差距可能会阻碍创新药物和仿制药的产品开发。在这篇综述中，讨论了关键释放控制赋形剂（PLGA）的可变性，以及用于 PLGA 聚合物和 PLGA 微球的先进物理化学表征技术。还总结了不同体外释放测试方法、体内药代动力学研究和体外-体内相关性开发的相对优缺点和挑战。本综述旨在深入了解长效微球产品，从而促进这些复杂产品的开发。
