肺靶向利福平壳聚糖磁微球的构建

Preparation of Lung Targetting Magnetic Chitosan Microspheres of Rifampin

控制微球粒径和外加磁场引导制备具有靶向于肺部的利福平壳聚糖磁微球。用超声混匀 -乳化 -化学交联技术制备 ,正交设计实验并引入理想函数对评价微球的重要质量指标进行归一化处理 ,得到较佳的制备工艺条件。在壳聚糖浓度、乳化剂用量一定的条件下 ,对总优化指数 DF影响最大的是原料配比 ,其次是搅拌速度和固化剂用量 ,而水 /油体积比则影响很小。经过优化制得的微球 ,在光镜下观察呈褐色且分散性良好 ,粒径为 1 2 .3 6± 4.6 8μm,DP为 0 .3 79,载药量和包封率分别为 8.80 % ,44.0 % ;在体外 40 0 0× 1 0 -4 T磁场作用下的运动距离是 6～ 8cm/min;其体外释放符合 Higuichi方程 ,Q=5 .3 4 3 3 t1/2 +3 .0 1 45 ,r=0 .9875。

This study is to prepare a new dosage form of rifampin which can target for lung site and has the characteristics of a slow-releasing drug. An emulsion-cross linking technique was used for the preparation, and orthogonal test method was used to optimize the preparation conditions. The desirability function (DF) was introduced as a total index for the multiple variable of microsphere formulation. If the chitosan's concentration and amount of emulsion remained constant, the influence of chitosan/magnetic/rifampin ratio, stirring speeds, cross-linking agent amount and W/O volume ratio on the overall index reduced successively. Under optimal conditions, the mean diameter was 12.36±4.68 μm; DP 0.379; the drug loading and the incorporation efficiency, 8.80% and 44.0%, respectively. In vitro studies indicated that its mobile velocity was 6~8cm/min in a magnetic field of 4000×10 -4T. The drug release profile in vitro could be described by Higuchi equation Q=5.3433 t 1/2+3.0145, r=0.9875.