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塞呋肟酸-L-精氨酸-环糊精三元包合物的理化性质和分子建模研究。

Physicochemical and molecular modeling studies of cefixime-L-arginine-cyclodextrin ternary inclusion compounds.

机构信息

Department of Pharmaceutical Chemistry, Government College of Pharmacy, Karad, Maharashtra, 415 124, India.

出版信息

Carbohydr Polym. 2013 Nov 6;98(2):1317-25. doi: 10.1016/j.carbpol.2013.07.070. Epub 2013 Aug 3.

Abstract

In an attempt to improve the physicochemical properties of cefixime (CEF), its supramolecular inclusion compounds were prepared with β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) in presence and/or absence of ternary component L-arginine (ARG) using spray drying technique. Initially, the phase solubility studies revealed a stoichiometry of 1:1 molar ratio with an AL-type of phase solubility curve. The stability constants of binary systems were remarkably improved in presence of ARG, indicating positive effect of its addition. The inclusion complexes were characterized by FTIR, XRPD, DSC, SEM, particle size analysis, and dissolution studies. Further, molecular mechanic (MM) calculations were performed to investigate the possible orientations of CEF inside βCD cavity in presence and/or absence of ternary component. In case of physicochemical studies, the ternary systems performed well as a result of comprehensive effect of ternary complexation and particle size reduction achieved by a spray drying technology.

摘要

为了改善头孢克肟(CEF)的物理化学性质,采用喷雾干燥技术,在β-环糊精(βCD)和羟丙基-β-环糊精(HPβCD)存在和/或不存在三元组分 L-精氨酸(ARG)的情况下,制备了其超分子包合物。首先,相溶解度研究表明,与 AL 型相溶解度曲线的摩尔比为 1:1。在添加 ARG 的情况下,二元体系的稳定常数得到显著提高,表明其添加具有积极影响。通过傅里叶变换红外光谱(FTIR)、X 射线粉末衍射(XRPD)、差示扫描量热法(DSC)、扫描电子显微镜(SEM)、粒度分析和溶解研究对包合物进行了表征。此外,还进行了分子力学(MM)计算,以研究 CEF 在存在和/或不存在三元组分的情况下在βCD 腔内的可能取向。在物理化学研究中,由于三元络合和喷雾干燥技术实现的粒径减小的综合作用,三元体系表现良好。

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