目的采用星点设计-效应面法优化盐酸青藤碱脉冲片处方。方法采用干法压制包衣法制备盐酸青藤碱脉冲片,以片芯中羧甲淀粉钠的用量、包衣处方中凝胶材料比例(羟丙甲纤维素∶卡拉胶)和凝胶材料用量为考察因素,以释药时滞为考察指标,采用星点设计安排实验,并对指标与因素进行多元线性和二项式数学拟合,通过效应面法预测最佳处方,并对其进行验证。结果指标与因素之间可采用二项式拟合,相关系数为0.993 7采用优化条件制备的3种处方的脉冲片均经一定时滞(6 h左右)后药物呈脉冲释放,释药时滞实测值与预测值偏差均在±4.43%以内。结论盐酸青藤碱脉冲片具有体外定时脉冲释药特性,星点设计-效应面优化法可用于本制剂的处方优化,所建立的数学模型预测性良好。

Objective To optimize the formulation of sinomenine hydrochloride pulsatile drug delivery tablets by central composite design-response surface method.Methods The tablets containing sinomenine hydrochloride were prepared by dry-compression coating technique.The influence factors included the amount of sodium carboxymethyl starch in core tablets, the ratio of HPMC/carrrageenan,and the amount of matrix materials in coating film.The evaluation parameter was lag time.Experiments were done on the central composite design,and the data were simulated using multi-linear equation and second-order polynomial equation.The possibly optimal formulation was predicted by response surface method.The lag time of the tablets prepared under the optimum condition was compared with the predicted.Results The lag time was simulated using second-order polynomial equation and the regression coefficient was 0.993 7.The lag time in vitro of the tablets prepared under the optimum conditions was about 6 h,then drug released in pulsatilerelease character.Bias between the observed and predicted values of the lag time was within ±4.43%.Conclusion The sinomenine hydrochloride pulsatile tablets could release drug quickly in vitro at the predetermined time.Central composite design-response surface method can be used to optimize the formulation and the model developed in this study proves to be highly predictable.