Manufacturing dexamethasone intravitreal implants: Process control and critical quality attributes.

Area of Science:

• Polymer science
• Drug delivery systems
• Biomaterials engineering

Background:

• Over 20 long-acting injectable formulations utilize poly(lactide-co-glycolide) (PLGA), a biodegradable polymer enabling drug release for up to six months.
• Despite commercial success, limited PLGA products exist, with no generic options due to manufacturing challenges in achieving equivalent drug release profiles.
• Developing chemically and structurally equivalent PLGA formulations to reference listed drugs (RLDs) presents significant hurdles for both in vitro and in vivo performance.

Purpose of the Study:

• To investigate the impact of manufacturing processes on the quality and performance of PLGA-based solid implants.
• To explore how controlling implant structural characteristics affects drug release and potency.
• To provide insights into the hot-melt extrusion process for developing novel and generic PLGA drug products.

Main Methods:

• Utilized Ozurdex (dexamethasone intravitreal implant) as a model system for PLGA-based solid implants.
• Employed a continuous hot-melt extrusion process, focusing on precise feeding control for dimensional accuracy.
• Evaluated five different extruder die designs to produce structurally distinct implants under identical extrusion conditions.

Main Results:

• Hot-melt extrusion process control was crucial for maintaining unit dose potency by managing implant diameter, internal porosity, and surface roughness.
• Structurally distinct implants produced via different die designs showed no alteration in in vitro drug release profiles in saline and phosphate-buffered saline (pH 7.4).
• Implant porosity was identified as a factor influencing the mechanical strength of the PLGA implants.

Conclusions:

• Precise control over the hot-melt extrusion process is essential for manufacturing consistent and effective PLGA-based solid implants.
• While structural variations did not affect drug release, porosity impacts mechanical properties, which is critical for implant integrity.
• This study offers valuable insights for the development of both innovative and generic PLGA long-acting injectable drug products.