中心复合设计法优化盐酸伪麻黄碱缓释微丸包衣液处方

Optimization of coating solution formulation of pseudoephedrine hydrochloride sustained-release pellets by a central composite design

目的:采用Eudragit RS30D对盐酸伪麻黄碱微丸进行缓释包衣,优化包衣液处方。方法:通过单因素考察,确定影响药物释放的主要因素,以综合评分值(Y)为评价指标,采用中心复合设计试验对包衣液处方进行优化,确立处方组成,并在优化区域内选择一点安排一次验证试验,以检验优化工艺条件的有效性。结果:理论包衣增重(X1)和抗黏剂滑石粉用量(X2)是影响药物释放的主要因素,其中理论包衣增重(X1)对评价指标有非常显著影响(P<0.01),拟合所得多元二次方程为Y=576.2-17.88X1-4.244X2+0.1449X12+0.06391X1X2+0.01080X22,r=0.9775。验证试验表明,本优化方程有良好的预测性。结论:中心复合设计法优化的制备条件良好,制得的盐酸伪麻黄碱缓释微丸的体外累积释放度符合要求。

Objective ：To optimize coating solution formulation using Eudragit RS30D and prepare pseudoephedrine hydrochloride sustained-release pellets. Methods：The formulation was developed based on a single-factor test, which was carried out to screen the critical influencing factors for the release rate. The optimal formulations were obtained by a central composite design. Results：The theoretical increment in coating weight （X1） and the anti-adhesive agent talc （X2 ） were the main factors which influenced the release rate. Among the two materials, the theoretical increment in coating weight （X1） affected the release rate more dramatically （P 〈 0.01 ）. The correlation equation was Y = 576.2 - 17.88X1 - 4. 244X2 ＋ 0. 144 9X21 ＋ 0. 063 91X1X2 ＋ 0. 010 80X22 and the correlation coefficient was 0. 977 5. Validation results showed that this equation was capable of prediction for optimization of the formulation. Conclusion ：The central composite design was able to optimize the coating solution formulation of pseudoephedrine hydrochloride sustained-release pellets.