基于药效学及正交试验优化复方益心酮口腔崩解片的处方与工艺

Optimization of prescription and process of compound Yixintong orally disintegrating tablets based on pharmacodynamic and orthogonal experiments

目的:考察并筛选复方益心酮口腔崩解片的处方与工艺,并对其进行优化。方法:通过建立小鼠常压耐缺氧模型,以小鼠心脏组织及脑组织中SOD、MDA、GSH-Px、CAT和存活时间为指标,筛选山楂叶提取物与冰片的复方配比;采用粉末直接压片法制备复方益心酮口腔崩解片;以崩解时限和口感为指标,通过单因素试验筛选处方中熔融比例、填充剂、崩解剂、助流剂、润滑剂、矫味剂的种类及用量,采用正交试验优化处方中主要影响因素崩解剂、润滑剂、矫味剂的用量,并对最优处方进行验证。结果:药效学实验结果表明,山楂叶提取物与冰片复方配比在19.2∶1~12.8∶1范围内具有较优的抗缺氧效果。最优处方组成为:山楂叶提取物与硬脂酸比例为1∶2、阿斯巴坦用量为3%、甘露醇用量为53.1%、交联羧甲基纤维素钠(CCMC-Na)用量为9%、硬脂酸镁用量为1.5%。所制口腔崩解片可在60 s内完全崩解,且口感良好。结论:基于药效学试验和正交设计优化所得的最优处方及制备工艺稳定可行,为复方益心酮口腔崩解片的后续研发提供依据。

OBJECTIVE The prescription and process of compound Yixintong orally disintegrating tablets were investigated,screened,and optimized.METHODS A mouse normobaric hypoxia tolerance model was established.SOD,MDA,GSH-Px,CAT levels in myocardium and brain tissues,and survival time were used as indicators to screen the compound ratio of Hawthorn leaf extract and borneol.Compound Yixintong orally disintegrating tablets were prepared using direct powder pressing method.The melt ratio,filler,disintegrating agent,flow aid,lubricant and flavoring agent in the prescription were screened by single-factor test with the disintegration time limit and taste as indicators.The dosage of disintegrating agent,lubricant and flavoring agent in the prescription was optimized by orthogonal experiment,and the optimal prescription was verified.RESULT The pharmacodynamic results showed that the compound ratio of Hawthorn leaf extract and borneol exhibited superior anti-hypoxia effect in the range of 19.2∶1~12.8∶1.The optimal prescription consisted of a 1∶2 ratio of Hawthorn leaf extract to stearic acid,3%of aspartame,53.1%of mannitol,9%of CCMC-Na and 1.5%of magnesium stearate.The resulting orally disintegrating tablets completely disintegrated within 60 seconds,and had a pleasing taste.CONCLUSION The optimal prescription and preparation process obtained based on pharmacodynamic experiments and orthogonal design are stable and feasible,which provides a basis for the subsequent research and development of compound Yixintong orally disintegrating tablets.