Veiga F, Fernandes C, Maincent P
Laboratório de Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, Portugal.
Drug Dev Ind Pharm. 2001 Jul;27(6):523-32. doi: 10.1081/ddc-100105177.
Tolbutamide (TBM) was found to form an inclusion complex with beta cyclodextrin (beta-CD) in solution and in solid state. Inclusion complex formation between tolbutamide and beta-cyclodextrin in aqueous solution was studied by phase solubility and spectral shift methods. The apparent stability constant Ks calculated by these techniques, in water, were estimated as 195.7 and 236.5 M(-1), respectively. The phase solubility studies revealed a B(S)-type diagram with an inclusion complex of 1:2 molar ratio. The solid inclusion complexes of TBM and beta-CD were prepared at a molar ratio of 1:2 by kneading, coprecipitation, freeze-drying, and spray-drying methods. In addition, the physical mixture was prepared. Characterization of TBM: beta-CD inclusion was performed using differential scanning calorimetry (DSC), Raman spectroscopy, and X-ray diffractometry and by application of a so-called ether wash method. All the inclusion systems investigated led to a significant improvement in the dissolution over free TBM, and the dissolution rate of the active material was observed to be independent of the preparation method.
发现甲苯磺丁脲（TBM）在溶液和固态下均能与β-环糊精（β-CD）形成包合物。采用相溶解度法和光谱位移法研究了甲苯磺丁脲与β-环糊精在水溶液中的包合物形成情况。通过这些技术计算得出，在水中的表观稳定常数Ks分别估计为195.7和236.5 M⁻¹。相溶解度研究揭示了一种B(S)型相图，其包合物的摩尔比为1:2。通过捏合、共沉淀、冷冻干燥和喷雾干燥法，以1:2的摩尔比制备了TBM与β-CD的固体包合物。此外，还制备了物理混合物。采用差示扫描量热法（DSC）、拉曼光谱法、X射线衍射法以及所谓的醚洗法对TBM:β-CD包合物进行了表征。所有研究的包合体系均使游离TBM的溶出度显著提高，且观察到活性物质的溶出速率与制备方法无关。
