响应面法优化复方降脂片的成型性工艺及其降脂活性

Optimization of Formability Process of Compound Lipid Lowering Tablets by Response Surface Methodology and Its Lipid Lowering Activity

目的:优化复方降脂片的成型性工艺,并对其降脂活性进行研究。方法;采用Box-Behnken响应面法,以复方降脂片提取物为主药,以脆碎度、崩解时限及溶出度为评价指标,对主药与填充剂的比例、崩解剂的用量及乙醇的浓度为影响因素,优化复方降脂片的成型性工艺。同时采用高脂血症大鼠模型评价复方降脂片的降脂活性。结果:最优成型性工艺为:主药与辅料比例为80∶15,崩解剂用量为5%,乙醇浓度为80%。验证实验结果:各批次样品综合评分为94.01%,与预测值相对误差为1.49%,且脆碎度和崩解时限均符合药典规定;降脂活性实验:与高脂模型组的实验数据相比,复方降脂片各剂量组大鼠血清中,除高密度脂蛋白(HDL-C)外,其他指标均呈下降趋势,其中高剂量组各指标水平均呈极显著下降(P<0.01);中剂量组AST、ALT水平呈极显著下降(P<0.01),TC、TG及LDL-C的水平显著下降(P<0.05),HDL-C水平增加,与模型组差异显著(P<0.05)。结论:本实验优选的成型性工艺,稳定可行,且复方降脂片降脂活性良好,本研究结果为复方降脂片的生产开发提供可靠依据。

Objective:To optimize the moldability process of compound lipid lowering tablets and to study its lipid-lowering activity.Methods:Using Box-behnken response surface method,the compound lipid lowering tablet extract as the main drug,with the friability,disintegration time and dissolution rate as the evaluation indicators,the ratio of the main drug to the filler,the amount of disintegrant and the concentration of ethanol as the influencing factor,the moldability process of compound lipid lowering tablets were optimized.At the same time,the hyperlipemia rat model was used to evaluate the lipid-lowering activity of compound lipid lowering tablets.Results:The ratio of main drug and auxiliary materials was 80∶15,the amount of disintegrant was 5%,and the concentration of ethanol was 80%.Verification experiment results:The comprehensive score of each batch was 94.01%,and the relative error with the predicted value was 1.49%,and the friability and disintegration time limit were in compliance with pharmacopoeia.Lipid lowering activity test results:Compared with the experimental data of high-fat model group,except for high-density lipoprotein(HDL-C),other indexes in serum of rats in each dose group of compound lipid lowering tablet showed a downward trend,among which the levels of each index in high-dose group significantly decreased(P<0.01),AST and ALT levels in medium dose group significantly decreased(P<0.01),TC,TG and LDL-C levels significantly decreased(P<0.01).The level of HDL-C in medium dose group increased,and had significant difference with the model group(P<0.05).Conclusion:The preferred molding process of this experiment is stable and feasible,and the lipid lowering activity of compound lipid lowering tablets is good.The results of this study provide a reliable basis for the production and development of compound lipid lowering tablets.