Spectrofluorimetric study of eflucimibe-gamma-cyclodextrin inclusion complex

Eur J Pharm Biopharm. 2005 Apr;59(3):523-6. doi: 10.1016/j.ejpb.2004.09.011.

Abstract

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.

MeSH terms

  • Anilides / analysis*
  • Anilides / chemistry*
  • Chemistry, Pharmaceutical
  • Hydrophobic and Hydrophilic Interactions
  • Spectrometry, Fluorescence / methods
  • Spectrometry, Gamma / methods
  • gamma-Cyclodextrins / analysis*
  • gamma-Cyclodextrins / chemistry*

Substances

  • Anilides
  • gamma-Cyclodextrins
  • eflucimibe