Title

A reproducible accelerated in vitro release testing method for PLGA microspheres

Authors

Jie Shen, University of ConnecticutFollow
Kyulim Lee, University of Connecticut
Stephanie Choi, Food and Drug Administration
Wen Qu, Food and Drug Administration
Yan Wang, Food and Drug Administration
Diane J. Burgess, University of Connecticut

Document Type

Article

Date of Original Version

2-10-2016

Abstract

The objective of the present study was to develop a discriminatory and reproducible accelerated in vitro release method for long-acting PLGA microspheres with inner structure/porosity differences. Risperidone was chosen as a model drug. Qualitatively and quantitatively equivalent PLGA microspheres with different inner structure/porosity were obtained using different manufacturing processes. Physicochemical properties as well as degradation profiles of the prepared microspheres were investigated. Furthermore, in vitro release testing of the prepared risperidone microspheres was performed using the most common in vitro release methods (i.e., sample-and-separate and flow through) for this type of product. The obtained compositionally equivalent risperidone microspheres had similar drug loading but different inner structure/porosity. When microsphere particle size appeared similar, porous risperidone microspheres showed faster microsphere degradation and drug release compared with less porous microspheres. Both in vitro release methods investigated were able to differentiate risperidone microsphere formulations with differences in porosity under real-time (37°C) and accelerated (45°C) testing conditions. Notably, only the accelerated USP apparatus 4 method showed good reproducibility for highly porous risperidone microspheres. These results indicated that the accelerated USP apparatus 4 method is an appropriate fast quality control tool for long-acting PLGA microspheres (even with porous structures).

Publication Title, e.g., Journal

International Journal of Pharmaceutics

Volume

498

Issue

1-2

Citation/Publisher Attribution

Shen, Jie, Kyulim Lee, Stephanie Choi, Wen Qu, Yan Wang, and Diane J. Burgess. "A reproducible accelerated in vitro release testing method for PLGA microspheres." International Journal of Pharmaceutics 498, 1-2 (2016): 274-282. doi: 10.1016/j.ijpharm.2015.12.031.