Spectrofluorimetric study of eflucimibe-γ-cyclodextrin inclusion complex

被引：22
作者：
Mesplet, N
Morin, P
Ribet, JP
机构：
[1] Univ Orleans, ICOA, UMR 6005, F-45067 Orleans, France
[2] Inst Rech Pierre Fabre, Castres, France
来源：
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2005年 / 59卷 / 03期
关键词：
eflucimibe; cyclodextrin; spectrofluorimetry; inclusion complex; stoichiometry; association constant;
D O I：
10.1016/j.ejpb.2004.09.011
中图分类号：
R9 [药学];
学科分类号：
1007 ;
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 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. (c) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码：523 / 526
页数：4
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