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

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 (R-2 = 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.