Effect of formulation variables on the prediction of release from microparticles with experimental design

Abstract

Different formulations of triamcinolone acetonide (TA) encapsulated in microparticles (MPs) based on poly(D,L-lactide-co-glycolide) (PLGA), poly(ϵ-caprolactone) (PCL), and poly(methyl vinyl ether-co-maleic anhydride) (Gantrez AN119) blends were obtained by spray-drying with a mixture experimental design. The goal of this study was to investigate the influence of the mixture composition, particle size, particle shape, enthalpy of melting (ΔHm) of PCL, enthalpy of depolymerization of PLGA, and glass-transition temperature of Gantrez on drug release at pH 1.2 and 6.8. The presence of Gantrez in the MPs made PCL more amorphous because of the reduction of its ΔHm. The determination of the activation energy (Ea) associated with TA release from the MPs was used to calculate the fitting equation of the drug-release profile, and subsequently, a thermodynamic (Arrhenius-like) model was established. Drug release increased as Ea and ΔHm decreased. Our results suggest that this approach was capable of predicting in vitro TA release from these MPs, which allowed us to develop formulations with low-release patterns at pH 1.2 and to modulate drug release at enteric pH. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4546–4553, 2006