基于药辅合一的葛根素川芎油亚微乳的研究

Puerarin-Chuanxiong oil submicron emulsion combining medicine and adjuvant

依据葛根和川芎的配伍作用研究药辅合一的亚微乳制剂的制备工艺,并对其物理药剂学性质进行评价。固定川芎油为油相,以微乳区面积为指标,采用滴水法绘制伪三元相图,筛选合适的乳化剂及助乳化剂制备川芎油亚微乳;以载油量为指标,优选最大载油的处方;再以葛根素替代部分表面活性剂,构建药辅合一的亚微乳制剂。测定所得亚微乳剂的粒径、电位、离心稳定性及放置稳定性,同时采用透析袋法对所得亚微乳制剂的释药行为进行考察,从而综合评价制得乳剂的质量。通过此法成功制备川芎油亚微乳剂,确定以聚氧乙烯蓖麻油-40为乳化剂,不添加助乳化剂;最大载油处方为川芎油∶聚氧乙烯蓖麻油-40∶水3∶7∶90;并成功进行葛根素对亚微乳制剂中乳化剂的替换,最大替换率为10%,最终确定的载药处方为葛根素∶川芎油∶聚氧乙烯蓖麻油-40∶水7∶30∶63∶900。对所得亚微乳剂的质量进行评价,结果显示所得乳滴的平均粒径为333.9 nm,PDI为0.26,Zeta电位为-10.12 mV,且离心稳定性良好。所得亚微乳放置50 d未见分层及析出等现象,稳定性良好。对其体外释药行为进行评价,亚微乳剂可完全释药。通过此法制得的葛根素-川芎油亚微乳制剂质量稳定,该乳剂体系可在一定程度上增大葛根素的溶解度,并体现一定的缓释作用。

This study was mainly based on the compatibility of Puerariae Lobatae Radix and Chuanxiong Rhizoma to prepare submicron emulsion and evaluated its physical and pharmaceutical properties.Firstly,pseudo-ternary phase diagrams were drawn by dripping method which took Chuanxiong oil as the oil phase and the area of microemulsion region as the index.On this basis,suitable emulsifier and co-emulsifier were screened for the preparation of Chuanxiong oil submicron emulsion.Then,the formula realizing the largest oil loading was selected.Finally,puerarin substituted part of emulsifier and co-emulsifier to lower their content,so as to form puerarin-Chuanxiong oil submicron emulsion featuring the combination of medicine and adjuvant.Its particle size,zeta potential,centrifugal stability and storage stability were determined,and the in vitro drug release behavior was investigated by dialysis bag method,based on which the quality of the as-prepared submicron emulsion was evaluated comprehensively.The proposed method was proved feasible for the preparation of Chuanxiong oil submicron emulsion,which adopted polyoxyethylene castor oil(EL-40)as the emulsifier and was free from co-emulsifier.The formula of the maximum oil loading was found as Chuanxiong oil∶EL-40∶water 3∶7∶90.Further,puera-rin successfully replaced up to 10%of the emulsifier in submicron emulsion.Eventually,the optimal drug-loading formula was determined as puerarin∶Chuanxiong oil∶EL-40∶water 7∶30∶63∶900.The quality evaluation results of the as-prepared submicron emulsion demonstrated that the average emulsion droplet size was 333.9 nm,the PDI 0.26,and the zeta potential-10.12 mV.The submicron emulsion had a good centrifugal stability and did not present any instable phenomena such as delamination and precipitation during its standing still for 50 days.The evaluation of in vitro drug release behavior indicated that the submicron emulsion was capable of releasing the drug completely.The puerarin-chuanxiong oil submicron emulsion prepared in this study possessed a stable quality and to some extent increased the solubility of puerarin along with a sustained-release effect.This study provided ideas for the clinical application of puerarin.