Pharmacy Department, Chemistry and Pharmacy Faculty, Central University of Las Villas, Cuba.
Int J Pharm. 2012 Dec 15;439(1-2):275-85. doi: 10.1016/j.ijpharm.2012.09.025. Epub 2012 Sep 16.
The objective of this study was to prepare and characterize complexes of 2-(2-nitrovinyl) furan (G-0) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD). The solid inclusion complexes were prepared using kneading and freeze-drying methods. Phase solubility profiles were used to obtain the apparent stability constants and the complexation efficiency. They were classified as A(L) type for both systems: the apparent stability constants K(1:1) of the complexes were 48.7 and 79.2 M(-1) for HP-β-CD and SBE-β-CD respectively. The solid inclusion complexes were evaluated by means of differential scanning calorimetry (DSC), X-ray diffraction (XRD) and nuclear magnetic resonance spectroscopy (NMR). Especially the use of the two-dimensional ROESY spectrum was useful to confirm the presence of an inclusion complex. The spatial configuration of the drug inside the cyclodextrin cavity was investigated using molecular modeling studies. The latter results were in agreement with the experimental data. Inclusion complexes of G-0 with HP-β-CD contributed to improve the chemical stability of the drug in the presence of other commonly used pharmaceutical excipients.
本研究的目的是制备和表征 2-（2-硝基乙烯基）呋喃（G-0）与 2-羟丙基-β-环糊精（HP-β-CD）和磺丁基醚-β-环糊精（SBE-β-CD）的包合物。采用捏合和冷冻干燥法制备固体包合物。利用相溶解度曲线得到表观稳定常数和包合效率。两种体系均属于 A(L)型：与 HP-β-CD 和 SBE-β-CD 形成的配合物的表观稳定常数 K(1:1)分别为 48.7 和 79.2 M(-1)。通过差示扫描量热法（DSC）、X 射线衍射（XRD）和核磁共振波谱（NMR）对固体包合物进行了评价。特别是二维 ROESY 谱的应用有助于确认包合物的存在。利用分子建模研究考察了药物在环糊精腔内的空间构象。后者的结果与实验数据一致。G-0 与 HP-β-CD 的包合物有助于提高药物在与其他常用药用辅料共存时的化学稳定性。
