Formulation and characterization of exenatide-loaded PLGA microspheres prepared by coacervation

Area of Science:

• Biomaterials Science
• Pharmaceutical Technology
• Drug Delivery Systems

Background:

• Bydureon® utilizes poly(lactide-co-glycolide) (PLGA) microspheres for sustained release of exenatide acetate, a GLP-1 receptor agonist.
• The precise impact of formulation variables on PLGA microsphere attributes and exenatide encapsulation remains incompletely understood.
• Optimizing microencapsulation processes is crucial for developing effective long-acting injectable therapies.

Purpose of the Study:

• To investigate the influence of key formulation parameters on the encapsulation of exenatide acetate within PLGA microspheres.
• To establish stable manufacturing conditions for PLGA microspheres with characteristics similar to Bydureon®.
• To develop a framework for the microencapsulation of peptides using coacervation.

Main Methods:

• Coacervation (phase separation) via a single-emulsion method was employed to formulate PLGA microspheres.
• Process variables including PLGA concentration, solvent ratios (DCM:water, DCM:Si oil), and hold times were screened.
• Formulation yield, residual solvent, encapsulation efficiency, and in vitro release profiles (24-hour burst and 56-day release) were evaluated.

Main Results:

• A PLGA concentration of 6% w/w and a 1-minute hold time were identified as optimal parameters.
• Formulations achieved high yields (>50%) and low initial burst release (2-6%) within 24 hours.
• The microspheres demonstrated sustained in vitro peptide release over 56 days, consistent with the commercial product.

Conclusions:

• A robust framework for PLGA microsphere formulation of exenatide acetate via coacervation was established.
• The optimized process yields microspheres with desirable encapsulation efficiency and controlled release profiles.
• These findings are applicable to the development of generic and novel peptide microencapsulations.