摘要
通过星点设计-效应面法优化洛索洛芬钠微丸的缓释包衣处方。以缓释包衣材料HPMC和EC的比例以及包衣增重为考察因素,1、4和8h的累积释放度为考察指标,分别用线性模型和非线性模型描述考察指标和因素之间的关系,绘制所选用模型的效应面和等高线图,根据设定的缓释释药目标值,通过重叠等高线图确定优化处方,最后进行验证。结果表明,非线性模型中的三次多项式是描述指标与因素之间的最佳模型。最佳处方微丸缓释包衣累积释放度的理论预测值与实测值偏差较小。可见,采用星点设计-效应面法得到的,基于多元非线性模型的洛索洛芬钠微丸缓释包衣处方优化模型,可以对该缓释微丸的处方进行优化,所建立的模型具有较好的预测能力和实用性。
The aim of the study was to optimize the coating formulation of sustained release pellets of loxoprofen sodium by the central composite design response surface methodology（RSM plus CCD）In the formulation design using RSM plus CCD. Independent variables were the ratio of HPMC to EC（X1）in the sustained coating formulation and polymer load（weight gain,X2） were selected as in dependent variables,andin vitroaccumulated releases from the pellets at 1,4,and 8 h were dependent variables Multilinear,two and three order quadratic models were used to estimate the relationship between the dependent and the independent variables,and to delineate RSM and overlay contour plots in order to select the optimal formulations in compliance to the hypothesized in vitro releases（%） at 1,4,and 8 hThe results showed that the relationship between dependent and independent variables was best fitted to three order quadratic equation.The regression equation generated for the hypothesized in vitro cumulative releases（%） at 1,4,and 8 h were Q1 h=227.699 2-30.785 9X1-43.395 4X2＋0.917 4X 1^2＋1.820 3 X2^2＋6.803 9X1X2-0.131 5X1^2X2-0.268 2X1X2^2,Q4 h=408.254 0-47.427 8X1-75.229 2X2＋3.304 0X2^2＋12.357 3X1X2-0.111 8X1^2X2-0.5425X1X2^2,Q8 h=303.539 0-30.417 6X1-45.114 0X2＋2.064 4X2^2＋6.865 0X1X2-0.334 1X1X2^2,respectively.In the optimized coating formulation,the ratio of HPMC to EC was 40% and the polymer load 90% Bias between observed and predicted values in vitro accumulated releases were negligible,indicating the high predictability of the selected models.Therefore,RSM plus CCD is applicable in the optimization of the coating formulation of loxoprofen sodium sustained-release pellets.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2010年第2期130-134,共5页
Journal of China Pharmaceutical University
关键词
洛索洛芬钠
缓释微丸
星点设计-效应面法
重叠等高线
loxoprofen sodium sustained release pellets central composite design response surface methodology overlay contour plot
