鞣花酸微球的制备及体外释放度考察

Preparation and in vitro Release of Ellagic Acid Microspheres

目的:优化鞣花酸微球的制备工艺并考察其体外释药机制,为该制剂的体内药物动力学研究提供参考。方法:采用HPLC测定鞣花酸含量,流动相乙腈-0.1%磷酸水(23∶77),检测波长254 nm。以微球释放度为考察指标,通过正交试验考察海藻酸钠、壳聚糖、氯化钙质量分数及海藻酸钠-药物质量比对鞣花酸微球处方工艺的影响,利用零级动力学方程、一级动力学方程和Higuchi方程进行体外释放度拟合。结果:最佳处方工艺为海藻酸钠-鞣花酸(3∶1),海藻酸钠2%,氯化钙2%,壳聚糖0.1%;微球在48 h内平均释放度80.14%,体外释放符合Higuchi方程Q=0.131t1/2-0.046 9(r=0.966 4)。结论:该处方工艺稳定可行、重复性好。鞣花酸微球体外释放具有缓释性能。

Objective： To optimize preparation process of ellagic acid mierospheres and investigate its in vitro release mechanism for pharmacokinetic. Method： HPLC was employed to determine the content of ellagic acid with mobile phase of acetonitrile-0. 1% phosphoric acid water （23： 77） and detection wavelength at 254 nm. Taking release as index, orthogonal test was adopted to optimize formulation process with contents of sodium alginate, chitosan, calcium chloride and mass ratio of sodium alginate-drug as factors, zero-order kinetics equation, first order kinetics equation and Higuchi equation were taken to fit in vitro release of ellagic acid microspheres. Result： Optimum formulation was as following ： sodium alginate to ellagic acid of 3 ： 1, sodium alginate of 2% , chitosan of 0. 1% , calcium chloride of 2%. Realease of ellagic acid microspheres was 80. 14% within 48 h, its in vitro release fitted Higuchi equation of Q = 0. 131t^1/2 -0. 046 9 （r =0. 966 4）. Conclusion： This optimized process is stable, practicable and repeatable. Ellagic acid microspheres show sustained release performance.