Impact of microparticle formulation approaches on drug burst release: a level A IVIVC

Abstract

Aim: To study the effect of poly(d,l-lactic-co-glycolic acid) (PLGA) microparticles (MPs) preparation techniques on particle physical characterization with special emphasis on burst drug release. Methods: A basic drug clozapine was used in combination with acid-terminated PLGA. Two approaches for MP preparation were compared; the in situ forming microparticle (ISM) and the emulsion-solvent evaporation (ESE) methods using an experimental design. The MPs obtained were compared according to their physical characterization, burst release and T_80%. An in vivo pharmacokinetic study with in vitro–in vivo correlation (IVIVC) was also performed for the selected formula. Results: Both methods were able to sustain drug release for three weeks. ISM produced more porous particles and was not effective as ESE for controlling burst release. A good IVIVC (R² = 0.9755) was attained when injecting the selected formula into rats. Conclusion: MPs prepared with ESE showed a minimum burst release and a level A IVIVC was obtained when administered to rats.

• Burst release
• factorial design
• in situ forming microparticles
• IVIVC
• polymer Tg
• uncapped PLGA

Acknowledgements

The authors wish to express their thanks to the staff members of the pharmacology and toxicology department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt, for their assistance in performing the in vivo study. The authors would also like to acknowledge PURAC Biochem, Apex Pharma and Sedico companies for supplying PLGA, clozapine and celecoxib, respectively, for this work.