Pan Jin-Huo, Wang Jian-Chun, Jiang Zhi-Tao, Zhang Ting, Ge Shao-Bo, Zhang Ye-Xia, Jin Xin, Yan Guo-Jun
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China ; Department of Pharmacy Office, Traditional Chinese Medicine Hospital of Zhang-jia-gang, Zhangjiagang 215600, China.
Department of Pharmacy Office, Traditional Chinese Medicine Hospital of Zhang-jia-gang, Zhangjiagang 215600, China.
Pharmacogn Mag. 2014 Jul;10(39):217-26. doi: 10.4103/0973-1296.137360.
The active ingredients of Ganershu compound recipe, which are effective for hepatitis treatment in liver protection and transaminase reduction. However, the active ingredients of Ganershu compound recipe are poor absorption, which conduct it has a low oral bioavailability.
We prepared Ganershu sustained-release pellets (GSPs) by fluidized-bed on central composite design-response surface methodology and increase its bioavailability in beagle dogs.
In this study, GSPs were successfully prepared. The Drug-loaded pellets and sustained-release coated were carried out in fluidized-bed machine. GSP was optimized for fitting release, roundness, and the overall desirability by central composite design-response surface methodology.
To optimize cumulative release profile, the outermost ethyl cellulose coating layer and the hydroxypropyl methyl cellulose (HPMC) swelling layer were employed, which were respectively given coating levels in terms of weight gain of 22% and 6%, the concentration of HPMC is 4.5% (g/ml). The pharmacokinetics of Ganershu normal pellets (GNPs) and GSP was studied in beagle dogs after oral administration. The naringenin as an index, the area under the curve0-∞ of naringenin in GSP was 1.38 times greater than that of GNP. Meanwhile, Tmax of GSP was prolonged for about 74%.
This study can clearly indicate that we enhanced the oral bioavailability of Ganershu by preparing the GSP, which had the sustained dissolution and improved the potential of it for clinical application.
肝儿舒复方制剂的有效成分对肝炎治疗具有保肝及降转氨酶作用。然而，肝儿舒复方制剂的有效成分吸收较差，导致其口服生物利用度较低。
采用流化床法结合中心复合设计-响应面法制备肝儿舒缓释微丸（GSPs），以提高其在比格犬体内的生物利用度。
本研究成功制备了GSPs。载药丸芯和缓释包衣在流化床设备中进行。采用中心复合设计-响应面法对GSP进行优化，以使其符合释放度、圆整度及综合可取性要求。
为优化累积释放曲线，采用最外层乙基纤维素包衣层和羟丙基甲基纤维素（HPMC）溶胀层，其增重包衣水平分别为22%和6%，HPMC浓度为4.5%（g/ml）。口服给药后，在比格犬体内研究了肝儿舒普通微丸（GNPs）和GSP的药代动力学。以柚皮苷为指标，GSP中柚皮苷的曲线下面积0至无穷大（AUC0-∞）是GNP的1.38倍。同时，GSP的达峰时间（Tmax）延长了约74%。
本研究表明，通过制备GSP提高了肝儿舒的口服生物利用度，其具有持续溶解特性，提高了其临床应用潜力。
