Box-Behnken效应面法优化盐酸左氧氟沙星胃漂浮缓释片处方

Optimized Formulation of Levofloxacin Gastric Floating Tablet by Box-Behnken Design

关键词:  左氧氟沙星  Box-Behnken设计  胃漂浮缓释片  效应面法

Key words:  levofloxacin  Box-Behnken design  gastric floating tablet  response surface methodology

摘要:

目的 探讨Box-Behnken效应面法在优化盐酸左氧氟沙星胃漂浮缓释片处方过程中的应用。方法 以盐酸左氧氟沙星为模型药物，采用湿法制粒压片法制备左氧氟沙星胃漂浮缓释片剂。利用Box-Behnken实验设计，考察3种缓释材料HPMC K4M、卡泊姆CP934P及海藻酸钠(SA)对不同时间点释药性能和漂浮片漂浮性能的影响，通过二项式方程拟合建立因素与响应值之间的数学关系以优化处方，对体外释药数据进行方程拟合，探讨其释药机理。结果 优化后的最佳处方为HPMC K4M 30%、卡泊姆CP934P 12.3%、SA 28.6%，优化处方的实测值与预测值之间的偏差较小；药物的释药机制为骨架溶蚀与药物扩散双重作用。结论 Box-Behnken效应面法优化法建立的模型可以用于盐酸左氧氟沙星缓释片处方的优化。

Abstract:

OBJECTIVE To explore the potential of utilization Box-Behnken design/response surface methodology in the optimization of levofloxacin gastric floating drug delivery system(GFDDS). METHODS Levofloxacin was selected as model drug and tablets were prepared by conventional wet granulation method. The influence of three different sustained-release matrixes such as HPMC K4M, Carbopol 934P and sodium alginate (SA) on the drug released characteristic at varied times and floating capability was performed by establishing second-order equation which was used to estimate the relationship between the independent and the dependent variables. The possibly optimal formulation was predicted by Box-Behnken design. The drug released mechanism of the tablet were studied by model-fitted of drug released with different equations. RESULTS Optimized formulation of famotidine gastric floating tablets was selected as 30% HPMC K4M, 12.3% Carbopol 934P and 28.6% SA. Bias between the observed and predicted values were little. A non-Fickian mechanism was found to be predominant, which indicated that water diffusion as well as polymer rearrangement played an essential role in drug release. CONCLUSION The quadratic mathematical model developed by Box-Behnken design could be used to optimize formulation of levofloxacin gastric floating tablets.