Role of PLGA Variability in Controlled Drug Release from Dexamethasone Intravitreal Implants

Long-acting injectable formulations based on poly(lactide-co­-glycolide) (PLGA) have been commercialized for over 30 years in the form of at least 20 FDA–approved products. These dosage forms offer several advantages over comparable formulations, including reduced dosing frequency, improved patient compliance, and maintenance of therapeutic levels of drug. However, the inherent complexity of the PLGA copolymer presents many of these challenges of developing PLGA-based long-acting products. Small changes to PLGA physicochemical properties and/or the drug product manufacturing process can have a major impact on the drug release profile of these long-acting formulations.

This work seeks to better understand how variability in the physicochemical properties of similar PLGAs affects drug release from PLGA solid implants using Ozurdex (dexamethasone intravitreal implant) as the model system. The PLGAs were extensively characterized using a variety of analytical techniques prior to implant manufacture using a continuous, hot melt extrusion process. In vitro release testing of the four structurally-equivalent implants was performed in both normal saline and phosphate-buffered saline, yielding drastically different results between the two methods. In normal saline, no differences in the release profiles were observed. In PBS, drug release profiles were sensitive to small changes in residual monomer content, carboxylic acid end group content, and blockiness of the polymers. This finding further emphasizes the need for a physiologically relevant in vitro release testing method as part of a robust quality control strategy for PLGA–based solid implant formulations.

Feng Zhang, Associate Professor at the Division of Molecular Pharmaceutics and Drug Delivery at College of Pharmacy, University of Texas, Austin