Key Factor Study for Generic Long-Acting PLGA Microspheres Based on a Reverse Engineering of Vivitrol®

Molecules

Hui Zhang¹  Yabing Hua¹  Aiping Zheng¹  Xiaoming Lin¹  Jing Gao¹  Zengming Wang¹  Dan Wang¹  Boshi Liu¹ 

[1] State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China, 27th Taiping Road, Haidian District, Beijing 100850, China;

关键词: PLGA microspheres;    reverse engineering;    Vivitrol^®;    generic naltrexone-loaded microspheres;    critical process parameters;   

DOI  :  10.3390/molecules26051247

来源: DOAJ

【 摘 要 】

The FDA (U.S. Food and Drug Administration) has approved only a negligible number of poly(lactide-co-glycolide) (PLGA)-based microsphere formulations, indicating the difficulty in developing a PLGA microsphere. A thorough understanding of microsphere formulations is essential to meet the challenge of developing innovative or generic microspheres. In this study, the key factors, especially the key process factors of the marketed PLGA microspheres, were revealed for the first time via a reverse engineering study on Vivitrol^® and verified by the development of a generic naltrexone-loaded microsphere (GNM). Qualitative and quantitative similarity with Vivitrol^®, in terms of inactive ingredients, was accomplished by the determination of PLGA. Physicochemical characterization of Vivitrol^® helped to identify the critical process parameters in each manufacturing step. After being prepared according to the process parameters revealed by reverse engineering, the GNM demonstrated similarity to Vivitrol^® in terms of quality attributes and in vitro release (f₂ = 65.3). The research on the development of bioequivalent microspheres based on the similar technology of Vivitrol^® will benefit the development of other generic or innovative microspheres.

【 授权许可】

Unknown