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

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 K1:1 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.

Graphical abstractA 1:1 inclusion coplex of trimethoprim with hydroxypropyl-γ-cyclodextrin was prepared, characterized and modeled by semiempirical methods. Phase solubility and characterization were carried out by standard methods.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We prepared a 1:1 trimethoprim/2-hydroxypropyl-γ-cyclodextrin inclusion. ► Complex formation in solution is exothermic and reaches equilibrium after 8 h. ► We modeled theoretically and characterized by ROESY method that TMP inclusion occurs with 2,3,4-trimethoxybenzyl ring inside HPγCD cavity.