摘要
通过Plackett-Burman联用Box-Behnken响应面法优化马来酸依那普利非洛地平双层片中非洛地平缓释层的处方。采用Plackett-Burman试验设计筛选对非洛地平累积释放率影响显著的处方因素,再用Box-Behnken响应面法对显著因素进一步优化,并进行二次多元回归拟合,预测最佳处方。结果表明羟丙甲纤维素、乳糖和聚氧乙烯40氢化蓖麻油对非洛地平的累积释放率影响显著,预测最优处方中乳糖用量为55 mg,羟丙甲纤维素(HPMC K4M)用量为96 mg,聚氧乙烯40氢化蓖麻油用量为1 mg,自制样品与参比制剂(Lexxel~?)中的非洛地平在多种介质中的释放曲线相似。该方法用于处方优化操作简便,预测性良好,试验结果符合要求。
Plackett-Burman combined with Box-Behnken response surface methodology was used to optimize the formulation of sustained-release layer of enalapril maleate and felodipine double-layer tablets. Plackett-Burman design was adopted to screen the major influential factors of the release of felodipine, then the selected factors were further investigated by Box-Behnken response surface methodology. The multiple linear regression and second-order quadratic models were established to predict the best formulation. The statistical data showed that hypromellose （HPMCK4M）, lactose and polyoxyl 40 hydrogenated castor oil had significant influences on the release of felodipine. The results of the significant analysis in Box-Behnken design was similar to that in Plackett-Burman design. Lactose and polyoxyl 40 hydrogenated castor oil had positive effects on the release of felodipine at 1, 4 and 7 h, in the opposite, HPMC had
a negative effect. The optimized formulation was achieved with HPMC of 55 mg, lactose of 96 mg, and polyoxyl 40 hydrogenated castor oil of 1 mg, the release profiles of felodipine from the home-made tablets were similar to those of the reference preparation （Lexxel？） in different release media. The method for optimizing the formulation was simple with good predictability, and its results met the requirements.
作者
王健松
席龙
叶伟文
邢盛
WANG Jiansong XI Long YE Weiwen XING Sheng(Baiyunshan Pharmaceutical General Factory, Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd., Guangzhou 510515)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2017年第6期854-860,共7页
Chinese Journal of Pharmaceuticals
基金
国家"重大新药创制"科技专项(2012ZX09202101-011)
广东省2012年第一批重大科技专项计划项目(2012A080204007)
