基于AHP-CRITIC的D-最优混料设计优化维药驱虫斑鸠菊乳膏处方研究

Optimization of formulation of Vernonia anthelmintica cream by D-optimal mixture design based on AHP-CRITIC analysis

目的筛选和优化驱虫斑鸠菊乳膏剂的处方。方法将白凡士林、液体石蜡和单硬脂酸甘油酯(GMS)在75℃水浴中加热至融化混合均匀作为油相;驱虫斑鸠菊有效部位(VAEP)先以聚氧乙烯40氢化蓖麻油(RH40)润湿后再加入水和二乙二醇单乙醚(Transcutol P)作为水相,水相在75℃水浴中加热后以细流状加入油相中,边加边搅拌,自水浴取出后继续搅拌至半固体状即得乳膏剂。以外观性状、涂展性、离心稳定性、耐寒耐热稳定性为评价指标,采用层次分析法(AHP)-基于指标相关性的指标权重确定方法(CRITIC)混合加权法确定各评价指标的权重系数,结合D-最优混料设计优化驱虫斑鸠菊乳膏的处方。按照最优处方制备不同载药量(1%、2%、4%、8%、16%)的乳膏,进行综合评分;制备载药量分别为1%、2%和4%的乳膏,4℃放置30 d,以HPLC法对乳膏中斑鸠菊大苦素和3,5-二咖啡酰奎宁酸的含量变化率进行初步考察。结果按AHP-CRITIC混合加权法得到外观性状、涂展性、耐热耐寒稳定性和离心稳定性的权重系数分别为13.18%、16.01%、38.93%、31.89%,结合D-最优混料设计确定驱虫斑鸠菊乳膏的最优处方为液体石蜡10%、凡士林45.48%、GMS 7.83%、RH4010.31%、Transcutol P 6.65%、水19.73%。驱虫斑鸠菊乳膏最大载药量为4%。乳膏中斑鸠菊大苦素和3,5-二咖啡酰奎宁酸含量变化率在30 d内均<4.3%。结论优化后的驱虫斑鸠菊乳膏外观均匀、半透明、细腻柔软,易于涂抹,稳定性好,制备工艺稳定可行。

Objective To screen and optimize the matrix prescription of Vernonia anthelmintica cream.Method Heating white vaseline,liquid paraffin,and glycerol monostearate(GMS)in a 75℃water bath until they are melted and mixed evenly as an oil phase.The effective fraction of V.anthelmintica(VAEP)was first moistened with polyoxyethylene 40 hydrogenated castor oil(RH40),and then added with water and diethylene glycol monoethyl ether(Transcutanol P)as the aqueous phase.The aqueous phase was heated in a water bath at 75℃,and then added in a thin stream to the oil phase,stirring while adding.After being taken out of the water bath,continue stirring until it was semi solid to obtain the cream.The weight coefficients of each evaluation index were determined using the Analytic Hierarchy Process(AHP)-Index Weight Determination Method Based on Index Correlation(CRITIC)hybrid weighting method,using the appearance characteristics,spreadability,centrifugal stability,and cold and heat resistance stability as evaluation indicators.The formulation of V.anthelmintica cream was optimized using the D-optimal mixture design.Prepare creams with different drug loads(1%,2%,4%,8%,and 16%)according to the optimal prescription,and conduct comprehensive scoring.The cream with drug loading of 1%,2%,and 4%was prepared and placed for 30 d at 4℃.The content change rate of vernonin and 3,5-dicaffeoylquinic acid in the cream was preliminarily investigated by HPLC.Results According to AHP CRITIC mixed weighting method,the weight coefficients of appearance characteristics,spreadability,heat and cold resistance stability,and centrifugal stability were 13.18%,16.01%,38.93%,and 31.89%,respectively.Combined with D-optimal mixture design,the optimal formulation of V.anthelmintica cream was determined to be liquid paraffin 10%,vaseline 45.48%,GMS 7.83%,RH4010.31%,Transitol P 6.65%,and water 19.73%.The maximum drug loading of V.anthelmintica cream was 4%.The change rate of the content of vernonia macrocephalin and 3,5-dicaffeoylquinic acid in the cream was less than 4.3%within 30 d.Conclusion The preferred V.Anthelmintica cream was uniform,translucent,delicate and soft,and easy to spread,with good stability,and the preparation process was stable and feasible.