盐酸川芎嗪羧甲基壳聚糖丝素蛋白微球的制备和体外释放特性

Preparation and in vitro Release Characteristics of Ligustrazine Hydrochloride Loaded Carboxymethyl Chitosan Silk Fibroin Microspheres

目的:制备一种包载盐酸川芎嗪的羧甲基壳聚糖丝素蛋白微球,以期延长药物的释放时间。方法:采用乳化-化学交联法制备盐酸川芎嗪羧甲基壳聚糖丝素蛋白微球;采用高效液相色谱法测定盐酸川芎嗪的含量;采用Box-Behnken设计-效应面法优化载药微球的制备工艺;考察盐酸川芎嗪注射液和载药微球的体外释放特性。结果:优化的制备工艺条件为:丝素蛋白质量浓度3.0 mg·ml^-1、盐酸川芎嗪质量浓度2.0 mg·ml^-1、搅拌速度600 r·min^-1;制得的载药微球的粒径为(34.4±2.3)μm、包封率为(67.6±1.3)%(n=4),与软件模型预测值接近,偏差绝对值均小于5%。盐酸川芎嗪注射液中的药物在60 min内已完全释放;而载药微球在30 min内药物快速释放,60 min后药物释放速率较缓慢,180 min时完全释放。载药微球在6种释放介质中的体外释放过程均符合Higuchi方程,体现出良好的缓释特性。结论:优化后的盐酸川芎嗪羧甲基壳聚糖丝素蛋白微球制备工艺简便易行,微球形态圆整,包封率载药量较高,体外释放具有缓释特性。

Objective: To prepare ligustrazine hydrochloride loaded carboxymethyl chitosan silk fibroin microspheres to prolong the drug release time. Methods: Ligustrazine hydrochloride loaded carboxymethyl chitosan silk fibroin microspheres were prepared by an emulsification-chemical crosslinking method;the content of ligustrazine hydrochloride was determined by HPLC;the preparation process of drug loaded microspheres was optimized by Box-Behnken design-response surface method;the in vitro release characteristics of ligustrazine hydrochloride injection and drug loaded microspheres were investigated. Results: The optimized preparation conditions were as follows: the silk fibroin concentration of 3.0 mg·ml^-1,the ligustrazine hydrochloride concentration of 2.0 mg·ml^-1,and the stirring speed of 600 r·min^-1. The diameter of microspheres was( 34.4±2.3) μm,and the encapsulation efficiency was( 67.6±1.3) %( n =4),which was close to the predicted value of software model with the absolute deviation less than 5%. The drug in ligustrazine hydrochloride injection was released completely within 60 min,while the drug loaded in the microspheres was released rapidly within 30 min with slower drug release rate after 60 min,and completely released at 180 min. The in vitro release rates of drug loaded microspheres in six release media were all in accordance with Higuchi equations with promising sustained release characteristics. Conclusion: The optimized preparation process of ligustrazine hydrochloride loaded carboxymethyl chitosan silk fibroin microspheres is simple,and the microspheres have round shape,high encapsulation efficiency and drug loading,and sustained in vitro release characteristics.