星点设计-效应面优化乳化交联法制备恩诺沙星壳聚糖微球

Optimization of emulsification crosslinking method of Enrofloxacin chitosan microspheres based on central composite design and response surface methodology

以平均粒径、载药量、包封率及总评归一值为评价指标,运用星点设计考察芯材比、油水相比、壳聚糖浓度对微球制备的影响,对结果进行二项式拟合,效应面法选取最佳工艺条件并进行预测分析。结果显示,最佳工艺条件为:油水相比为4.2∶1,壳聚糖浓度为2%,交联时间为3.5 h。在此条件下,制得的微球粒径均一,球形圆整,平均粒径为7.21μm,包封率为61.34%,载药量为70.12%。体外释放行为符合Higuchi方程,2 h和24 h时累积释放率分别为32%和84%。

Microspheres were prepared by emulsification crosslinking method. The effects of the time of crosslinking,the ratio of oil phase to water phase and the concentration of chitosan,on mean diameter,entrapment efficiency,drug loading and overall desirability were investigated by using central composite design and response surface method. The data were imitated using multi-linear equation and second-order polynomial equation. The result shows that the optimal conditions were as follows： the ratio of oil phase to water phase was 4. 2∶1,the concentration of chitosan was 2% and the time of crosslinking as 3. 5 h. Under this condition,the microspheres prepared by optimal condition were round and uniform with main particle size of 7. 21 μm. The entrapment efficiency was 61. 34% and the drug loading reached 70. 12%. The in vitro release of the product fitted to Higuchi equation. The cumulative amount at 2 h and 24 h were 32% and 84%,respectively.