D-最优混料设计优化复方甘草微乳制备工艺的研究
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摘要
为增加复方甘草汤中挥发油的溶解度,提高其治疗慢性湿疹的疗效,该实验拟将其制成微乳制剂。以挥发油为微乳油相,提取液为微乳水相,通过绘制伪三元相图得到微乳区域面积与体系的最大容水比,进而确定表面活性剂和助表面活性剂的种类以及二者的质量比K_m。以微乳粒径、有效成分皮肤滞留量为指标,采用D-最优混料设计法对微乳处方进行优化,进而考察了优选处方的体外释药行为。结果显示,微乳中表面活性剂和助表面活性剂分别选择聚氧乙烯脱水山梨醇单油酸酯(Tween-80)和无水乙醇效果最好;K_m为1时,形成微乳区域面积最大;提取液质量浓度为0.5 g·m L-1时,对微乳的粒径分布影响最小。优选处方为9.4%Tween-80,9.4%无水乙醇,1.0%薄荷油,80.2%的0.5 g·m L-1提取液,所制得微乳黏度较小、稳定性良好,药物皮肤滞留量较高;体外释放实验结果表明,微乳对于甘草酸、甘草苷具有一定的缓释作用,基本达到了课题预期目的。
In order to increase the solubility of essential oil in compound licorice microemulsion and improve the efficacy of the decoction for treating chronic eczema,this experiment intends to prepare the decoction into microemulsion. The essential oil was used as the oil phase of the microemulsion and the extract was used as the water phase. Then the microemulsion area and maximum ratio of water capacity was obtained by plotting pseudo-ternary phase diagram,to determine the appropriate types of surfactant and cosurfactant,and K_mvalue-the mass ratio between surfactant and cosurfactant. With particle size and skin retention of active ingredients as the index,microemulsion prescription was optimized by D-optimal design method,to investigate the in vitro release behavior of the optimized prescription. The results showed that the microemulsion was optimal with tween-80 as the surfactant and anhydrous ethanol as the cosurfactant. When the K_mvalue was 1,the area of the microemulsion region was largest while when the concentration of extract was 0. 5 g·m L-1,it had lowest effect on the particle size distribution of microemulsion. The final optimized formulation was as follows: 9. 4%tween-80,9. 4% anhydrous ethanol,1. 0% peppermint oil and 80. 2% 0. 5 g·m L-1 extract. The microemulsion prepared under these conditions had a small viscosity,good stability and high skin retention of drug; in vitro release experiment showed that microemulsion had a sustained-release effect on glycyrrhizic acid and liquiritin,basically achieving the expected purpose of the project.
In order to increase the solubility of essential oil in compound licorice microemulsion and improve the efficacy of the decoction for treating chronic eczema,this experiment intends to prepare the decoction into microemulsion. The essential oil was used as the oil phase of the microemulsion and the extract was used as the water phase. Then the microemulsion area and maximum ratio of water capacity was obtained by plotting pseudo-ternary phase diagram,to determine the appropriate types of surfactant and cosurfactant,and K_mvalue-the mass ratio between surfactant and cosurfactant. With particle size and skin retention of active ingredients as the index,microemulsion prescription was optimized by D-optimal design method,to investigate the in vitro release behavior of the optimized prescription. The results showed that the microemulsion was optimal with tween-80 as the surfactant and anhydrous ethanol as the cosurfactant. When the K_mvalue was 1,the area of the microemulsion region was largest while when the concentration of extract was 0. 5 g·m L-1,it had lowest effect on the particle size distribution of microemulsion. The final optimized formulation was as follows: 9. 4%tween-80,9. 4% anhydrous ethanol,1. 0% peppermint oil and 80. 2% 0. 5 g·m L-1 extract. The microemulsion prepared under these conditions had a small viscosity,good stability and high skin retention of drug; in vitro release experiment showed that microemulsion had a sustained-release effect on glycyrrhizic acid and liquiritin,basically achieving the expected purpose of the project.
引文
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[11]尚华,关淑婷.复方甘草酸苷联合雷公藤多甙治疗急慢性湿疹的疗效观察[J].宁夏医科大学学报,2017,39(6):719.
[12]张丽华,陈燕,方雪梅,等.氧化苦参碱软膏对小鼠慢性湿疹的影响[J].中国药师,2017,20(1):46.
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[14]杜红.中药微乳载药体系关键技术研究[D].北京:北京中医药大学,2008.
[2]沈宝贤,曾运繁,林羽,等.复方甘草酸苷治疗慢性湿疹临床疗效观察[J].中国社区医师:医学专业,2011,13(36):183.
[3]张文娟.利福平微乳的研制[D].杨凌:西北农林科技大学,2006.
[4]李学敏,王琼,兰颐,等.微乳技术对止痛凝胶膏剂中成分释放和含量变化的影响[J].中国中药杂志,2013,38(16):2614.
[5]Ge S M,Lin Y Y,Lu H Y,et al.Percutaneous delivery of econazole using microemulsion as vehicle:formulation,evaluation and vesicle-skin interaction[J].Int J Pharm,2014,465(1):120.
[6]郭亚丽,李芳,洪媛,等.D-最优混料试验设计优化模拟米制品的配方[J].食品科技,2015,40(9):164.
[7]高丽琼,舒文娟,高缘,等.D-最优混料设计优化阿莫罗芬自乳化基质乳膏及乳膏流变学研究[J].中南药学,2010,8(7):481.
[8]翟志光.以良附丸为模型药物的中药复方微乳载药体系研究[D].北京:北京中医药大学,2007.
[9]李学敏,王琼,兰颐,等.微乳技术对止痛凝胶膏剂中成分释放和含量变化的影响[J].中国中药杂志,2013,38(16):2614.
[10]Du H,Feng Q J,Yang X Z,et al."Whole Chinese angelica"microemulsion:its preparation and in vivo and in vitro evaluations[J].Drug Dev Ind Pharm,2014,40(10):1330.
[11]尚华,关淑婷.复方甘草酸苷联合雷公藤多甙治疗急慢性湿疹的疗效观察[J].宁夏医科大学学报,2017,39(6):719.
[12]张丽华,陈燕,方雪梅,等.氧化苦参碱软膏对小鼠慢性湿疹的影响[J].中国药师,2017,20(1):46.
[13]Pakpayata H,Nielloud F,Fortune R,et al.Formulation of ascorbic acid microemulsions with alkyl polyglycosides[J].Eur J Pharm Biopharm,2009,72(35):444.
[14]杜红.中药微乳载药体系关键技术研究[D].北京:北京中医药大学,2008.