The main objective of the current research was to develop a compendial flow-through cell apparatus based in vitro release testing method for sustained-release triamcinolone acetonide-loaded poly (lactic-co-glycolic) acid (PLGA) microspheres. Media-based and instrument-based parameters, such as surfactant type, concentration, media volume, flow rate, and testing temperature, were investigated. In addition, a detailed exploration was performed to reveal polymer degradation encompassing pore formation, channeling, and triamcinolone acetonide release from microspheres using freeze-fracture scanning electron microscopy. The developed USP apparatus 4 method demonstrated more than 85% drug release from the microspheres in 12 days and showcased reproducibility between different microsphere batches. Large medium volume (15 times saturation solubility) at low surfactant concentration was identified as a critical media-based parameter, with potential application in testing of other sensitive poorly soluble drugs. At 35 °C, drug release via pore channeling to the surface was evident, whereas at 39 °C, drug release slowed due to polymer plasticization. It was demonstrated here for the first time that elevated temperature-accelerated testing does not work for all PLGA-based microsphere products.
Keywords: Flow-through cell apparatus; In vitro release testing; Polymeric microspheres; Triamcinolone acetonide.
Copyright © 2020 Elsevier B.V. All rights reserved.