蛇床子素β-环糊精包合物分散片的制备及大鼠体内药动学研究  

Preparation and pharmacokinetics in rat of osthol-β-CD inclusion complex dispersible tablets

作　　者：王周丽[1] 贝永燕[1] 朱爱军[1] 陈维良[1] 施林森[1] 张学农[1] 

机构地区：[1]苏州大学药学院药学系,江苏苏州215123

出　　处：《中成药》2012年第10期1887-1892,共6页Chinese Traditional Patent Medicine

基　　金：国家自然基金资助项目(81273463);江苏省科技支撑计划(BE2011670);国家大学生创新性试验计划(111028533;微机编号5731503311)

摘　　要：目的制备蛇床子素β-环糊精包合物以提高蛇床子素的水溶性,并考察体外释药特性及大鼠体内的药动学行为。方法采用逆向混合搅拌法制备蛇床子素β-环糊精包合物,以崩解时限、硬度及溶出度为综合指标L9(34)正交实验,高效液相色谱法测定大鼠体内的血药浓度。结果最终确定优选处方的辅料比例为10%微晶纤维素(MCC),6%低取代羟丙基纤维素(L-HPC)和12%交联聚维酮(PVPP);所制备的包合物分散片的崩解时间(52.7±2.4)s,硬度(5.13±0.47)kg,1 h内的累积溶出度(93.1±1.2)%;大鼠体内原料药组的Tmax为2.65 h,Cmax为2.87μg/mL,AUC0-24为21.32μg.h/mL,包合物分散片组的Tmax为2.14 h,Cmax为36.64μg/mL,AUC0-24为272.41μg.h/mL,经配对t检验,Tmax、Cmax、AUC0-24差异均有显著性(P<0.05)。结论蛇床子素包合物分散片具有溶散快,分散均匀,有效成分溶出速率快的特性,并能提高其大鼠体内生物利用度。AIM To prepare the inclusion complex of osthol-β-cyclodextrin for improving its solubility in water,and to study the release characteristics in vitro and pharmacokinetics in rats.METHODS The inclusion complex of osthol with β-CD was manufactured by counter mixture stirring method.The orthogonal design was used for the experiment with disintegration,hardness and dissolution of tablets as markers.The blood concentration of osthol in rat was assayed by HPLC.RESULTS The proportion of each adjuvant in the optimal formulation consisted of 10% MCC,6% L-HPC,12% PVPP.The optimized inclusion complex dispersible tablets disintegrated in（52.7±2.4） s,the hardness was（5.13±0.47） kg,and the accumulative dissolving quantity was（93.1±1.2）% in 1 h.The parameters were： Tmax of 2.65 h,Cmax of 2.87 μg/mL,AUC0-24 of 21.32 μg·h/mL in the osthol group,Tmax of 2.14 h,Cmax of 36.64 μg/mL,AUC0-24 of 272.41 μg·h/mL in the inclusion complex dispersible tablets group.The results of t test showed that there were significant differences in the Tmax,Cmax,AUC0-24 between two groups data（P0.05）.CONCLUSION Osthol-β-CD inclusion complex dispersible tablets have the characteristics of the fast and homogeneously dispersing,and the quick releasing of the active constituent,and increase bioavailability of osthol in rat.

关 键 词：蛇床子素β-环糊精包合物 分散片 正交设计 体外释药 药动学 

分 类 号：R969.1[医药卫生—药理学]