Fernández L, Martínez-Ohárriz M C, Martín C, Vélaz I, Sánchez M, Zornoza A
Departamento de Química y Edafología, Facultad de Ciencias, Universidad de Navarra, Irunlarrea s/n, Pamplona 31080, Spain.
J Pharm Biomed Anal. 2008 Aug 5;47(4-5):943-8. doi: 10.1016/j.jpba.2008.02.029. Epub 2008 Mar 2.
The interactions of gemfibrozil with gamma- and HP-gamma-cyclodextrin (CD) 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 gemfibrozil 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(s) and A(L) 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 gemfibrozil 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.
已通过荧光光谱法、核磁共振光谱法以及溶解度测量在水溶液中研究了吉非贝齐与γ-环糊精和羟丙基-γ-环糊精（HP-γ-CD）的相互作用，并通过X射线衍射、热分析和傅里叶变换红外光谱法在固态下进行了研究。讨论了用于络合分析的技术的影响。在γ-环糊精和羟丙基-γ-环糊精（HP-γ-CD）存在下，吉非贝齐的荧光增强，尤其是后者，因为1H NMR证明芳香环包合在空腔中对药物的激发态有保护作用。荧光增强使得能够测定pH 2.8时的结合常数。络合是一个由熵和焓驱动的过程。用γ-环糊精和HP-γ-CD得到的溶解度图分别为B(s)型和A(L)型。将25℃时由溶解度数据计算得到的表观稳定常数与荧光测定得到的表观稳定常数进行了比较。发现用γ-环糊精增溶药物除了包合现象外还涉及其他因素。通过捏合、共蒸发和共沉淀方法得到了吉非贝齐与γ-环糊精（而非HP-γ-CD）的固体络合物。固体络合物在通道结构中结晶，该过程涉及羧基和芳基醚基团。
