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

Area of Science:

• Biomaterials Science
• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Poly(lactide-co-glycolide) (PLGA) based long-acting injectables are widely used, offering benefits like reduced dosing frequency and improved patient compliance.
• Developing generic PLGA formulations with equivalent drug release profiles to reference drugs remains challenging due to the copolymer's complexity.
• Minor changes in PLGA properties or manufacturing can significantly alter drug release kinetics in these formulations.

Purpose of the Study:

• To investigate how variations in physicochemical properties of similar poly(lactide-co-glycolide) (PLGA) impact drug release from solid implants.
• To utilize the Ozurdex (dexamethasone intravitreal implant) as a model system for evaluating PLGA variability effects on drug release.
• To assess the suitability of different in vitro release testing methods for characterizing PLGA-based implants.

Main Methods:

• Four structurally equivalent dexamethasone intravitreal implants were prepared using different acid-terminated 50:50 PLGA copolymers with similar molecular weights.
• Extensive characterization of PLGA polymers was performed using various analytical techniques before implant manufacturing via hot-melt extrusion.
• In vitro drug release testing was conducted using normal saline and phosphate-buffered saline (PBS) to compare release profiles.

Main Results:

• No significant differences in drug release profiles were observed when testing implants in normal saline.
• In phosphate-buffered saline (PBS), drug release profiles exhibited sensitivity to subtle changes in PLGA's residual monomer content, carboxylic acid end group content, and blockiness.
• The study highlights the critical influence of specific PLGA physicochemical properties on drug release behavior.

Conclusions:

• Physicochemical variability in poly(lactide-co-glycolide) (PLGA) significantly affects drug release from solid implants, particularly in physiologically relevant media like PBS.
• The choice of in vitro release testing medium is crucial, as normal saline may not adequately capture formulation sensitivities.
• A physiologically relevant in vitro release testing method is essential for robust quality control of PLGA-based solid implant formulations.