Enhancing Initial Release of Peptide from Poly(d,l-lactide-co-glycolide) (PLGA) Microspheres by Addition of a Porosigen and Increasing Drug Load

Abstract

The objective of this study was to evaluate formulation variables such as drug load and addition of a porosigen in achieving an increased initial release of peptide from poly(d,l-lactide-co-glycolide) (PLGA) microspheres by altering carrier characteristics. Leuprolide acetate-loaded PLGA microspheres were prepared by a solvent-extraction–evaporation process and were characterized for their drug load (HPLC assay), bulk density (tapping method), size distribution (dynamic light scattering), specific surface area (Brunauer–Emmett–Teller [BET] analysis), surface morphology (scanning electron microscopy), in vitro drug release (at 37°C), and in vivo efficacy (suppression of rat serum testosterone). Increasing the drug load, and adding various amounts of calcium chloride to organic and aqueous phases of the emulsion during processing yielded particles with increased porosity, lower bulk density, higher specific surface area, and accordingly higher initial release. In an animal model, these formulations showed a faster onset of testosterone suppression compared to microspheres without higher drug load or calcium chloride. The approaches employed in this study were found to be effective in avoiding the therapeutic lag phase usually observed with microencapsulated macromolecular drugs.

Keywords:

• Drug load
• In vitro characteristics
• In vivo efficacy
• Leuprolide acetate
• Peptide
• PLGA microspheres
• Porosigen