Analysis of the complexation of gemfibrozil with gamma- and hydroxypropyl-gamma-cyclodextrins

作者：Fernandez L; Martinez Oharriz M C; Martin C; Velaz I; Sanchez M; Zornoza A^*

来源：Journal of Pharmaceutical and Biomedical Analysis, 2008, 47(4-5): 943-948.

DOI：10.1016/j.jpba.2008.02.029

• gemfibrozil
• inclusion complexation
• gamma-cyclodextrins
• binding constants

The interactions of gernfibrozil with gamma- and HP-gamma-cyclodextrin (CID) have been studied in aqueous solution by fluorescence and NMR spectroscopy and by solubility measurements and in the solid state by X-ray diffraction, thermal analysis and FTIR spectroscopy. The influence of the technique employed in the analysis of complexation is discussed. The fluorescence of gernfibrozil increased in the presence of gamma- and hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD), especially with the later, because the inclusion of the aromatic ring in the cavity. evidenced by 1H NMR, has a protective effect on the excited state of the drug. The fluorescence enhancement allowed the determination of the binding constants at pH 2.8. Complexation was a both entropy and enthalpy driven process. The solubility diagrams obtained with gamma-CD and HP-gamma-CD were B, and AL type, respectively. The apparent stability constants calculated from the solubility data at 25 degrees C were compared with those obtained from the fluorescence assays. It was found that drug solubilization with gamma-CD involves other contributions together with the inclusion phenomena. Solid complexes of gernfibrozil with gamma-CD (and not with HP-gamma-CD) have been obtained by kneading, coevaporation and coprecipitation methods. The solid complexes crystallised in the channel structure, in a process involving the carboxyl and aryl-ether groups.

• 出版日期2008-8-5