Spectrofluorimetric study of eflucimibe-gamma-cyclodextrin inclusion complex.
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 20 M(-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.
Mesplet
Nathalie
N
Institut de Chimie Organique et Analytique (I.C.O.A), Université d'Orléans, Orléans, France.
Morin
Philippe
P
Ribet
Jean-Paul
JP
D000813:Anilides / Q000032:analysis* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D057927:Hydrophobic and Hydrophilic Interactions; D013050:Spectrometry, Fluorescence / Q000379:methods; D013051:Spectrometry, Gamma / Q000379:methods; D047408:gamma-Cyclodextrins / Q000032:analysis* / Q000737:chemistry*
D000813:Anilides; D047408:gamma-Cyclodextrins; C418062:eflucimibe