Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Here we report the preparation of a trimethoprim/2-hydroxypropyl-gamma-cyclodextrin inclusion complex along with a physicochemical study, structural characterization, and molecular modeling of the complex. As main results, we observed from phase-solubility studies at two temperatures (20 degrees C and 35 degrees C) that the association constants decrease with increasing temperature. Values for K-1:1 constant were of the same magnitude order of those found for the parent gamma-CD. The inclusion orientation as evidenced by ROESY measurements involves the inclusion of the 3.45-trimethoxybenzyl ring in the CD cavity from the larger rim. This is in agreement with semiempirical molecular modeling calculation. (C) 2011 Elsevier B.V. All rights reserved.86101106FinepConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FapitecConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)