Potential use of supramolecular cyclodextrins for the design of patient- friendly super-generic drug formulations

2-羟丁基-β-环糊精（HB-β-CyD）是在2-羟丙基-β-环糊精（HP-β-CyD）的取代基上多了一个亚甲基的羟烷基化β-CyD衍生物。研究了HB-β-CyD的表面活性、吸湿性、溶血性和对难溶性药物的增溶能力等理化和生物学性质，并与HP-β-CyD进行了比较。然后，各种CyD和硬脂氧醚羟丙基甲基纤维素（SangeloseR）的组合使用，以提高口腔崩解片（ODTs）的可用性进行了研究。格列美脲是一种有效的第三代降糖药，由于其线性结构长，水溶性差，生物半衰期短，因此被用作模型药物。溶解度和NMR研究表明，格列美脲与CyD形成水溶性复合物，其中稳定常数的大小顺序为HB-β-CyD > HP-β-CyD > β-CyD > γ-CyD D D

2-Hydroxybutyl-β-CyD (HB-β-CyD) is a new hydroxyalkylated β-CyD derivative that has one more methylene group in the substituent of 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD). Some physicochemical and biological properties of HB-β-CyD, such as surface activity, moisture sorption, hemolytic activity and solubilizing ability for poorly water-soluble drugs were studied in comparison with those of HP-β-CyD. Then, a combined use of various CyDs and stearoxy ether of hydroxypropylmethylcellulose (SangeloseR) was investigated to improve usability of orally disintegrating tablets (ODTs). Glimepiride, a potent third generation hypoglycemic agent for type 2 diabetes was used as a model drug, because it is poorly water-soluble with long linear structure and biological half life is short. Solubility and NMR studies demonstrated that glimepiride formed water-soluble complexes with CyDs, where the magnitude of the stability constant increased in the order of HB-β-CyD > HP-β-CyD > β-CyD > γ-CyD D