Solid-state characterization of sertraline base-β-cyclodextrin inclusion complex
Solid-state characterization of sertraline base-β-cyclodextrin inclusion complex
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DOI：
10.1016/j.jpba.2014.12.036
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发表时间：
2015-03-25
影响因子：
3.4
通讯作者：
Ueda, Haruhisa
中科院分区：
文献类型：
--
作者：
Ogawa, Noriko;Hashimoto, Takuro;Ueda, Haruhisa
舍曲林是一种抗抑郁药，可有效治疗抑郁症、强迫症、恐慌症和社交恐惧症。它以其盐酸盐的形式销售，其在水中的溶解度比其游离碱形式更好。然而，舍曲林通过生物膜的吸收可以通过提高其碱的溶解度来改善，因为它比盐酸舍曲林更疏水。为了阐明舍曲林碱与β-CD的相互作用机制，研究β-CD环与舍曲林碱之间的基本相互作用是重要的。因此，在本研究中，将目前使用的盐酸盐形式转化为游离碱，并将β-CD用作β-CD衍生物的模型，以评价β-CD与舍曲林碱之间的相互作用。采用相溶解度法、差示扫描量热法、傅立叶变换红外光谱、傅立叶拉曼光谱、粉末X射线衍射和C-13交叉极化魔角旋转核磁共振等方法研究了舍曲林-β-环糊精复合物的固态物理化学性质。结果表明，舍曲林碱与β-CD形成包合物，固态舍曲林碱-β-CD包合物的化学计量比为1：1，这是通过溶解在DMSO-d（6）（C）2014 Elsevier B. V.中的包合物的H-1 NMR测量估计的。
Sertraline is one of the serotonin-specific reuptake inhibitors that is effective in treating several disorders such as major depression, obsessive-compulsive disorder, panic disorder, and social phobia. It is marketed in the form of its hydrochloride salt, which exhibits better solubility in water than its free base form. However, the absorption of sertraline through biological membranes could be improved by enhancing the solubility of its base because it is more hydrophobic than sertraline hydrochloride. To clarify the mechanism for the interaction of sertraline base with beta-CD, it is important to study the basic interaction between the beta-CD ring and sertraline base. Therefore, in this study, the currently used hydrochloride salt form was converted into the free base and beta-CD was used as a model for beta-CD derivatives to evaluate the interaction between beta-CD and the sertraline base. The solid-state physicochemical characteristics of the sertraline-beta-CD complex were investigated by the phase solubility method, differential scanning calorimetry, Fourier transform IR spectroscopy, FT-Raman spectroscopy, powder X-ray diffraction, and C-13 cross-polarization magic-angle spinning NMR measurements. The results showed that sertraline base and beta-CD form an inclusion complex, and the stoichiometric ratio of the solid-state sertraline base-beta-CD complex is 1:1, which was estimated by the H-1 NMR measurements of the complex dissolved in DMSO-d(6) (C) 2014 Elsevier B.V. All rights reserved.