普罗布考自微乳释药系统处方优化及体内外评价  

Formulation optimization of probucol self-microemulsifying drug delivery system and its in vitro and in vivo evaluation

作　　者：马俐丽[1] 朱照静[1,2] 匡扶[1] 吴青[1] 

机构地区：[1]重庆医科大学药学院 [2]重庆医药高等专科学校,重庆400016

出　　处：《中国药科大学学报》2009年第1期41-46,共6页Journal of China Pharmaceutical University

摘　　要：目的:制备符合口服要求的普罗布考自微乳化释药系统(PB-SMEDDS)。方法:测定表观油/水分配系数和溶解度、绘制伪三元相图筛选自微乳化基质,正交设计筛选最佳处方,测定自乳化速率、Zeta电位等理化参数,并考察体外溶出行为、稳定性及大鼠在体肠吸收。结果:PB-SMEDDS最佳处方组成为自微乳化基质(肉豆蔻酸异丙酯:Cremophor EL:La-brasol=30∶52.5∶17.5)和普罗布考15%。自微乳平均粒径(39.77±0.67)nm,自微乳化时间(52.33±0.47)s,Zeta电位-0.389 3 mV,室温下稳定,45 min药物释放达98.45%,释药曲线符合Hixson-Crowell方程。PB-SMEDDS在大鼠小肠的主要吸收部位为空肠和回肠,以被动吸收为主;PB-SMEDDS在小肠的吸收显著高于原料药(P<0.05)。结论:SMEDDS可显著改善普罗布考体外溶出度,增加在大鼠体内的吸收。Aim： To study the optimized formulation of probucol self-microemulsifying drug delivery system（ PB- SMEDDS） intended for oral administration. Methods： The apparent partition oil/water coefficients of probucol and solubility in the oils were determined, and pseudo-ternary phase diagrams were plotted. The formulation of PB-SMEDDS was optimized using the orthogonal design. The self-microemulsifying time, Zeta potentials and the stability of PB-SMEDDS were estimated. In vitro release and in situ rat intestinal absorption of PB-SMEDDS were determined. Results： The optimized formation of PB-SMEDDS was composed of IPM-Cremophor EL-Labrasol （30：52. 5： 17.5） and probucol 15%. PB-SMEDDS was indicated to have the mean particle size of （39. 77 ± 0. 67） nm, Zeta potential of - 0. 389 3 mV, and the time of self-microemulsifying of （ 52. 33±0. 47） s. PB- SMEDDS was found to be stable at ambient temperature. The percentage of accumulated dissolution of PB- SMEDDS was up to 98.45% at 45 min, and the profile curve fits the Hixson-Crowell equation. In addition, it was shown that the jejunum and ileum were the main absorption segments of PB-SMEDDS and that the absorption mechanism is attributed to passive diffusion. Moreover, the absorption of PB-SMEDDS is significantly higher than that of PB（ P 〈 0. 05）. Conclusion： SMEDDS were potential drug carrier for probucol for improving in vitro dissolution and the in vivo absorption in rat evidently.

关 键 词：普罗布考 自微乳化释药系统 处方优化 溶出度 在体肠吸收 

分 类 号：R944[医药卫生—药剂学]