College of Chinese Material Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.
Drug Dev Ind Pharm. 2009 Dec;35(12):1452-9. doi: 10.3109/03639040903002151.
The aim of this study was to prepare the inclusion complex of genipin (GP) and beta-cyclodextrin (beta-CD) with improved stability, solubility, and bioavailability and to study the pharmacokinetics of beta-CD inclusion complex in mice.
Lyophilization was employed in the preparation of the inclusion complex of GP-beta-CD, whose formation was confirmed by infrared, ultraviolet, differential scanning calorimetry, X-ray diffraction, and phase solubility method. Comparative studies on the in vitro solubility and stability and in vivo evaluation of GP in mice were investigated. Liquid-liquid extraction was used for the isolation of GP in the assay of its concentration. After injection in the caudal vein at equal doses of the inclusion complex of free GP, the drug concentration in mice plasma at fixed time after administration was determined by high-performance liquid chromatography method.
The results demonstrated that GP-beta-CD solid powders showed improved stability and solubility in aqueous solution, when comparing with free GP. The results of the in vivo study showed that the inclusion complex of GP-beta-CD exhibited the dissimilar pharmacokinetics from that of free GP after intravenous administration. The inclusion complex of GP-beta-CD displayed longer MRT(0-infinity) and higher AUC(0-infinity) than free GP did.
The relative bioavailability of the inclusion complex of GP-beta-CD to free GP was 305.3%, which demonstrated that GP formulations containing beta-CD significantly increased the bioavailability.
本研究旨在制备京尼平（GP）与β-环糊精（β-CD）的包合物，以提高其稳定性、溶解度和生物利用度，并研究其在小鼠体内的药代动力学。
采用冷冻干燥法制备 GP-β-CD 包合物，通过红外、紫外、差示扫描量热法、X 射线衍射和相溶解度法进行包合物形成的确认。对其体外溶解度和稳定性以及体内 GP 在小鼠体内的评价进行了比较研究。采用液-液萃取法分离测定其浓度。在等剂量尾静脉注射游离 GP 包合物后，采用高效液相色谱法测定给药后固定时间小鼠血浆中的药物浓度。
结果表明，与游离 GP 相比，GP-β-CD 固体粉末在水溶液中显示出更好的稳定性和溶解度。体内研究结果表明，静脉注射后 GP-β-CD 包合物的药代动力学与游离 GP 不同。GP-β-CD 包合物的 MRT（0-无穷大）和 AUC（0-无穷大）均高于游离 GP。
GP-β-CD 包合物相对于游离 GP 的相对生物利用度为 305.3%，表明含有β-CD 的 GP 制剂显著提高了生物利用度。
