Physicochemical study and characterization of the trimethoprim/2-hydroxypropyl-γ-cyclodextrin inclusion complex.

Abstract Here we report the preparation of a trimethoprim/2-hydroxypropyl-γ-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 °C and 35 °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 γ-CD. The inclusion orientation as evidenced by ROESY measurements involves the inclusion of the 3,4,5-trimethoxybenzyl ring in the CD cavity from the larger rim. This is in agreement with semiempirical molecular modeling calculation.