Spectrofluorimetric study of eflucimibe-gamma-cyclodextrin inclusion complex.

摘要

Eflucimibe, a novel and highly potent acyl-coenzyme A cholesterol O-acyl-transferase (ACAT) inhibitor, is sparingly soluble in aqueous media and exhibits a very weak natural fluorescence. However, when increasing concentrations of gamma-cyclodextrin (gamma-CD) are added, an increase in the fluorescence signal is observed, attesting the formation of a non-covalent inclusion complex between eflucimibe and the gamma-CD. In this work, the stoichiometry of the complex and the corresponding association constant have been determined from fluorescence data by Benesi-Hildebrand's method (double reciprocal plots). As a result, a 1:1 stoichiometric ratio and a 20M(-1) formation constant were obtained. This apparent formation constant was determined in water containing 10% methanol, which was needed to improve 'aqueous' solubility of the drug in a CD-free medium. Owing to the extreme hydrophobicity of eflucimibe, these results provide valuable information for pharmaceutical formulation studies.