星点设计-效应面法优化灯盏花素胃漂浮片的处方

Optimization of Formulation of Breviscapine Gastric-floating Tablets by Central Composite Design-response Surface Methodology

目的:采用星点设计-效应面法优选灯盏花素胃漂浮片的处方。方法:在单因素试验基础上,以羟丙基甲基纤维素K4M(HPMC K4M)和乳糖用量为考察因素,灯盏花素在第2,6,10 h释放度的综合评分为评价指标,通过星点试验优选灯盏花素胃漂浮片的处方,运用SAS软件对试验数据进行处理,选择最佳数学模型,采用Statistica 6.0软件绘制三维效应面图和等高线图,确定最优处方。结果:最佳处方为灯盏花素10 mg,HPMC K4M(亲水凝胶骨架)20 mg,乳糖(致孔剂)10 mg,碳酸氢钠(起泡剂)15 mg,十八醇(助漂剂)10 mg,微晶纤维素(填充剂)35 mg;HPMC K4M和乳糖用量分别为20%,10%。灯盏花素胃漂浮片在第2,6,10 h的释放度分别为19.2%,39.7%,81.5%,能在5 s内起漂,持续漂浮>10 h。结论:建立的数学模型预测性良好,可用于灯盏花素胃漂浮片处方的优化。制备的胃漂浮片释药要求符合规定,漂浮性能良好。

Objective：To optimize formulation of breviscapine gastric-floating tablets by central composite design-response surface methodology.Method：Based on single factor tests,with amounts of hydroxypropyl methyl cellulose K4M （HPMC K4M） and lactose as independent variables,synthesized estimated value which was calculated by release of breviscapine at 2,6 and 12 h as dependent variable,formulation of breviscapine gastric-floating tablets was optimized by central composite design,SAS software was adopted to process experimental data in order to choose optimum mathematical mode,Statistica 6.0 software was employed to draw 3D surface plot and contour plot for determination of optimum formulation.Result：Optimum formulation was：breviscapine 10 mg,HPMC K4M （hydrophilic gel matrix） 20 mg,lactose （porogenic agent） 10 mg,NaHCO3 （frothing agent） 15 mg,octadecanol （floating assistant） 10 mg,microcrystalline cellulose （filler）35 mg; and amounts of HPMC K4M and lactose were 20％ and 10％,respectively.Cumulative release of breviscapine gastricfloating tablets at 2,6 and 10 h were 19.2％,39.7％ and 81.5％,respectively.Breviscapine gastric-floating tablets could float in 5 s with duration of floating was more than 10 h.Conclusion：This established mathematical model had high predictability,which could be used to optimize formulation of breviscapine gastric-floating tablets.These prepared gastric-floating tablets had good release requirements and floating properties.