Nakai Y, el-Said Aboutaleb A, Yamamoto K, Saleh S I, Ahmed M O
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Chem Pharm Bull (Tokyo). 1990 Mar;38(3):728-32. doi: 10.1248/cpb.38.728.
Inclusion complexes of clobazam with alpha-, beta-, gamma-cyclodextrins (CyDs) and heptakis(2.6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD) in aqueous solution and in the solid phase were studied by the solubility method, infrared (IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffractometry. In addition, inclusion complex of clobazam with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin and the solid dispersion of clobazam with methyl cellulose (MC) in a ground mixture were investigated by IR, DSC and X-ray diffractometry. It was observed that DM-beta-CyD had the highest stability constant among the four CyDs in solution. Thermal and X-ray diffraction analyses showed that clobazam molecules existed in a molecularly dispersed state in the ground mixture of CyDs. Infrared spectra showed lower frequency shifts in the case of the ground mixtures of clobazam with natural CyDs, which can be attributed to the formation of hydrogen bonds between the two carbonyl groups of clobazam and hydroxyl groups of natural CyDs. In contrast, higher frequency shifts were observed in the case of the ground mixtures of clobazam with methylated CyDs and MC and these were considered to be due to the monomolecular dispersion of clobazam in a hydrophobic environment. The mode of interaction of clobazam with DM-beta-CyD was different from that with natural CyDs in the ground mixtures. Furthermore, the crystalline inclusion complex of clobazam with DM-beta-CyD was obtained by heating of the coprecipitate in vacuo at 120 degrees C for 1 h.
采用溶解度法、红外光谱（IR）、差示扫描量热法（DSC）和X射线衍射法，研究了氯巴占与α-、β-、γ-环糊精（CyDs）以及七（2,6-二-O-甲基）-β-环糊精（DM-β-CyD）在水溶液和固相中形成的包合物。此外，还通过IR、DSC和X射线衍射法研究了氯巴占与七（2,3,6-三-O-甲基）-β-环糊精形成的包合物以及氯巴占与甲基纤维素（MC）在研磨混合物中的固体分散体。结果发现，在溶液中，DM-β-CyD在四种环糊精中具有最高的稳定常数。热分析和X射线衍射分析表明，氯巴占分子以分子分散状态存在于环糊精的研磨混合物中。红外光谱显示，氯巴占与天然环糊精的研磨混合物中频率位移较低，这可归因于氯巴占的两个羰基与天然环糊精的羟基之间形成了氢键。相反，氯巴占与甲基化环糊精和MC的研磨混合物中观察到较高的频率位移，这些被认为是由于氯巴占在疏水环境中的单分子分散所致。在研磨混合物中，氯巴占与DM-β-CyD的相互作用模式与天然环糊精不同。此外，通过在真空中于120℃加热共沉淀物1小时，获得了氯巴占与DM-β-CyD的晶体包合物。
