Binding, Molecular Mechanics, and Thermodynamics of Cyclodextrin Inclusion Complexes with Ketoprofen in Aqueous Medium

ABSTRACT The purpose of this work was to study the interaction forces involved in the inclusion processes of ketoprofen with several cyclodextrins and to assess the best cyclodextrin for complexing this antiinflammatory drug. The behavior of the inclusion complexes of ketoprofen with α-, β-, and γ-cyclodextrins was studied by UV-VIS direct spectroscopy, 'H NMR, and molecular mechanics. Thermodynamic parameters for the binding processes were obtained from the temperature variations in binding constants, which manifest that "nonclassical" hydrophobic interactions are the main forces involved in these inclusion processes. Binding constants show that β- and γ-cyclodextrins form more stable 1:1 complexes with ketoprofen than does a-cyclodextrin. 1H NMR spectra show that the inclusion degree depends on the size of the internal diameter of cyclodextrin. The geometries calculated on the bases of molecular mechanics for these three-dimensional models indicate high stability.