Different formulations of triamcinolone acetonide (TA) encapsulated in microparticles (MPs) based on poly(D,L-lactide-co-glycolide) (PLGA), poly(epsilon-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 (Delta H-m) 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 Delta H-m. The determination of the activation energy (E-a) 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 E-a and Delta H-m 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. (c) 2006 Wiley Periodicals, Inc.