The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
Carbohydr Polym. 2013 Jun 20;95(2):733-9. doi: 10.1016/j.carbpol.2013.02.038. Epub 2013 Mar 1.
This study investigates the solubility of baicalein (Ba) with the addition of modified cyclodextrins using phase solubility method. The solubility of Ba in the presence of natural (α-, β-, and γ-) cyclodextrins and its derivatives, namely, hydroxypropyl-β-cyclodextrin (HP-β-CD) and (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), was higher than that of free Ba. In particular, the stability constant of inclusion complex with DM-β-CD was 13672.67l mol(-1), which was the highest among the examined cyclodextrins. The inclusion complexes of Ba and DM-β-CD were prepared via freeze-drying method, which were both characterized in the solution and solid state by UV-vis spectroscopy, differential scanning calorimetry (DSC), proton nuclear magnetic resonance ((1)H NMR), scanning electron microscopy (SEM), and X-ray powder diffractometry (XRPD). The UV-vis, DSC, (1)H NMR, SEM, and XRPD results proved the formation of inclusion complex between Ba and DM-β-CD. Furthermore, the dissolution rate and thermal stability of the inclusion complex were significantly enhanced compared with the pure drug. Therefore, using DM-β-CD can effectively improve the solubility and thermal stability of free Ba, which is a promising approach to promote its clinical application.
本研究采用相溶解度法考察了修饰环糊精对黄芩素（Ba）溶解度的影响。在天然（α-、β-和γ-）环糊精及其衍生物，即羟丙基-β-环糊精（HP-β-CD）和（2,6-二-O-甲基）-β-环糊精（DM-β-CD）存在下，Ba 的溶解度高于游离 Ba。特别是，与 DM-β-CD 的包合稳定常数为 13672.67l mol(-1)，在研究的环糊精中最高。通过冷冻干燥法制备了 Ba 和 DM-β-CD 的包合物，并通过紫外可见光谱、差示扫描量热法（DSC）、质子核磁共振波谱（(1)H NMR）、扫描电子显微镜（SEM）和 X 射线粉末衍射（XRPD）在溶液和固态下对其进行了表征。紫外可见、DSC、(1)H NMR、SEM 和 XRPD 结果证明了 Ba 与 DM-β-CD 之间形成了包合物。此外，与纯药物相比，包合物的溶解速率和热稳定性显著提高。因此，使用 DM-β-CD 可以有效提高游离 Ba 的溶解度和热稳定性，这是促进其临床应用的一种有前途的方法。
