Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Int J Pharm. 2011 Nov 28;420(2):191-7. doi: 10.1016/j.ijpharm.2011.08.027. Epub 2011 Aug 22.
Effects of p-hydroxybenzoate (paraben) ester chain length on the stoichiometry and structure of grinding-induced inclusion complexes with cholic acid (CA) were investigated. Physicochemical properties of the ground mixture were evaluated by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, and solid-state nuclear magnetic resonance (NMR) measurements. Ethyl-, n-propyl-, and isopropyl-parabens formed equimolar inclusion complexes with CA, and the complex structures were of the β-trans bilayer type. In contrast, the stoichiometry of the CA-paraben complex was 2:1, and the structure was of the α-gauche bilayer type when isobutylparaben was used as a guest molecule. Although the stoichiometries and structures of the complexes differed, solid-state NMR showed that the molecular states of parabens in the complexes were similar and independent of the ester chain length. Complexes between CA and parabens with longer substituent groups (C >4) were not observed. Steric effects induced by increasing the guest size are likely to influence the overall structure of inclusion complexes. Mechanical forces and thermal activation by grinding were important factors in the mechanism of CA-paraben complex formation.
研究了对羟基苯甲酸酯（尼泊金酯）酯链长对与胆酸（CA）形成的研磨诱导包合物的化学计量和结构的影响。通过粉末 X 射线衍射（PXRD）、差示扫描量热法（DSC）、傅里叶变换红外（FT-IR）光谱和固态核磁共振（NMR）测量评估了研磨混合物的物理化学性质。乙基、正丙基和异丙基对羟基苯甲酸酯与 CA 形成等摩尔包合物，其结构为β-反式双层型。相比之下，当使用异丁基对羟基苯甲酸酯作为客体分子时，CA-对羟基苯甲酸酯复合物的化学计量比为 2:1，结构为α- gauche 双层型。尽管复合物的化学计量比和结构不同，但固态 NMR 表明复合物中对羟基苯甲酸酯的分子状态相似，且与酯链长无关。未观察到 CA 与具有更长取代基（C>4）的对羟基苯甲酸酯之间的复合物。增大客体尺寸引起的空间位阻效应可能会影响包合物的整体结构。机械力和研磨引起的热激活是 CA-对羟基苯甲酸酯复合物形成机制中的重要因素。
