Fathy M, Sheha M
Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Egypt.
Pharmazie. 2000 Jul;55(7):513-7.
The complex formation of amylobarbitone (AMB) with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated in aqueous solution and in the solid state. The apparent stability constant for complex formation (Kc) calculated by phase solubility and spectral shift methods was 524 M-1 and 568 M-1, respectively. The stoichiometric molar ratio of the complex was estimated to be 1:1 and the solubility of AMB in water was increased about 3 fold. The solid dispersion system of AMB/HP-beta-CD in 1:1 molar ratio was prepared by a freeze-drying method. Differential scanning calorimetry (DSC), x-ray diffractometry, (IR) and 1H NMR spectroscopy were used to confirm that inclusion between the drug and HP-beta-CD occurred. The dissolution behavior of the drug as a physical mixture as well as the prepared complex, showed enhanced drug dissolution properties of the prepared complex compared to the physical mixture or the drug alone. The dissolution rate appeared in the first 2 min, 25 times greater for the complex than for the drug alone. Furthermore, in-vivo study revealed that the duration and hypnotic activity of AMB after its oral administration to mice were improved by inclusion.
研究了戊巴比妥（AMB）与2-羟丙基-β-环糊精（HP-β-CD）在水溶液和固态下的络合形成。通过相溶解度和光谱位移法计算的络合形成表观稳定常数（Kc）分别为524 M-1和568 M-1。估计络合物的化学计量摩尔比为1:1，AMB在水中的溶解度增加了约3倍。通过冷冻干燥法制备了摩尔比为1:1的AMB/HP-β-CD固体分散体系。采用差示扫描量热法（DSC）、X射线衍射法、红外光谱（IR）和1H NMR光谱法来确认药物与HP-β-CD之间发生了包合作用。作为物理混合物以及制备的络合物的药物溶解行为表明，与物理混合物或单独的药物相比，制备的络合物具有增强的药物溶解性能。在最初2分钟内，络合物的溶解速率比单独的药物快25倍。此外，体内研究表明，通过包合作用，AMB口服给药给小鼠后的持续时间和催眠活性得到了改善。
