title: A reproducible accelerated in vitro release testing method for PLGA microspheres.
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).
authors.affiliation: School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Kyulim
authors.initials: K
authors.lastname: Lee
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD 20993, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Choi
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD 20993, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Qu
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD 20993, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA. Electronic address: d.burgess@uconn.edu.
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Burgess
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D019344:Lactic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015203:Reproducibility of Results
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Accelerated in vitro release; Compositionally equivalent; PLGA microspheres; Porous; Risperidone; USP apparatus 4