Preparation, characterization, and pharmacokinetics of the inclusion complex of genipin-β-cyclodextrin
Preparation, characterization, and pharmacokinetics of the inclusion complex of genipin-β-cyclodextrin
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DOI：
10.3109/03639040903002151
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发表时间：
2009-01-01
影响因子：
3.4
通讯作者：
Wang, Shaomin
中科院分区：
文献类型：
--
作者：
Lu, Yi;Zhang, Tong;Wang, Shaomin
目的：制备稳定性、溶解度和生物利用度均得到改善的吉尼平与β -环糊精包合物，并研究β -环糊精包合物在小鼠体内的药动学。方法：采用冻干法制备gp - β - cd包合物，通过红外、紫外、差示扫描量热、x射线衍射和相溶解度法对包合物的形成进行证实。对GP在小鼠体内的溶解度、稳定性和体内评价进行了比较研究。采用液液萃取法分离GP，测定其浓度。将等量游离GP包合物注入尾静脉后，用高效液相色谱法测定给药后固定时间小鼠血浆中药物浓度。结果：与游离GP相比，GP- β - cd固体粉末在水溶液中具有更好的稳定性和溶解度。体内研究结果表明，静脉给药后GP- β - cd包合物与游离GP表现出不同的药代动力学。与游离GP相比，GP- β - cd包合物的MRT0-infinity更长，AUC（0-infinity）更高。结论：GP- β - cd包合物与游离GP的相对生物利用度为305.3%，表明含有β - cd的GP制剂可显著提高GP制剂的生物利用度。
Objective: 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. Methods: 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. Results: 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 MRT0-infinity and higher AUC(0-infinity) than free GP did. Conclusions: 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.