以油包水型微乳为载体促进氟尿嘧啶的经皮渗透  

Water in oil microemulsions for transdermal delivery of fluorouracil

作　　者：刘芳[1] 肖衍宇[1] 平其能[1] 杨闯[1] 

机构地区：[1]中国药科大学药剂学教研室,江苏南京210009

出　　处：《药学学报》2009年第5期540-547,共8页Acta Pharmaceutica Sinica

摘　　要：以磺化琥珀酸二辛酯钠(AOT)为主要表面活性剂,制备氟尿嘧啶油包水型微乳制剂,以促进药物的经皮渗透。以伪三元相图为基础,依据微乳区域大小,初步筛选微乳处方;用改进的Franz扩散池和离体小鼠皮肤研究氟尿嘧啶的透皮速率,以单位面积的透皮累积渗透量(Qn)为指标,考察微乳处方中助表面活性剂的种类、水相比例、混合表面活性剂比例、表面活性剂和助表面活性剂质量比和载药量对离体鼠皮透皮吸收的影响,优化处方。结果表明,氟尿嘧啶微乳的优化处方为含药0.5%(w/v),水30%,混合表面活性剂(AOT/Tween 85,Km=2)20%,油相(IPM)49.5%,经皮渗透符合一级速率方程,12h累积渗透量为(1355.5±41.1)μg.cm-2,分别为0.5%药物水溶液和2.5%(w/w)市售乳膏(O/W)的19.1和7倍。水/AOT/Tween 85/IPM微乳系统能促进5-氟尿嘧啶的透皮吸收,可以作为氟尿嘧啶等亲水性但水溶性差和渗透性差的药物的新型经皮给药载体。An Aersol-OT （AOT） included microemulsion containing fluorouracil was prepared by using appropriate proportion of oil, co-surfactant and water for increasing the drug transdermal delivery ability. According to the area of microemulsion basing on the pseudo-tertiary phase diagrams, the optimum formulation was screened initially. And the permeation flux of fluorouracil across excised mice skin was determined in vitro using Franz diffusion cell to optimize the formulation further. The effect of the kind of co-surfactant, the content of water, the content of mixed surfactant, the mass ratio of surfactant/cosurfactant （Kin） and the drug load on skin permeation of fluorouracil were evaluated. The optimum formulation was composed of 0.5% （w/v） fluorouracil, 30% water, 20% mix-surfactant （AOT/Tween 85, Km= 2） and 49.5% oil （IPM）. The cumulative amount permeated of fluorouracil in 12 hour was 1 355.5 μg·cm^-2, 19.1 folds and 7 folds more than 0.5% fluorouracil aqueous solution and 2.5% （w/w） fluorouracil cream, respectively. The permeation of this microemulsion accorded with first-order model. The water/AOT/Tween 85/IPM microemulsion system promoted the permeation of fluorouracil greatly, which may be a promising vehicle for the transdermal delivery of fluorouracil and other hydrophilic drug.

关 键 词：氟尿嘧啶 微乳 透皮给药 磺化琥珀酸二辛酯钠 

分 类 号：R943.4[医药卫生—药剂学]