含电解质的W/O型微乳作为氟尿嘧啶透皮给药载体的研究  

Water in oil microemulsions containing NaCl for transdermal delivery of fluorouracil

作　　者：肖衍宇[1] 刘芳[1] 陈志鹏[2] 平其能[1] 

机构地区：[1]中国药科大学药剂教研室,江苏南京210009 [2]南京中医药大学药剂教研室,江苏南京210046

出　　处：《药学学报》2011年第6期720-726,共7页Acta Pharmaceutica Sinica

基　　金：国家"重大新药创制"科技重大专项(2009ZX09310-004);中央高校基本科研业务费专项资金资助(JKQ2009018)

摘　　要：通过电解质氯化钠(NaCl)的加入,制备含水量高、载药量高且透过能力强的氟尿嘧啶(5-Fu)W/O型微乳,并研究其体外透皮特性及皮肤刺激性。以肉豆蔻酸异丙酯(IPM)为油相,磺化琥珀酸二辛酯钠(AOT)为表面活性剂,Tween 85为助表面活性剂,在室温下采用磁力搅拌法滴加NaCl溶液至油相中,形成空白微乳后直接加入5-Fu粉末,即形成5-Fu微乳。以伪三元相图为基础、单位面积的透皮累积透过量(Qn)为指标,用改进的Franz扩散池和离体小鼠皮肤考察微乳处方中含水量和载药量对离体鼠皮透过量的影响,优化处方。以表面张力、黏度和电导率为指标,研究NaCl/AOT-Tween 85/IPM微乳的理化性质,并对最优处方的皮肤刺激性进行初步评价。结果表明,5-Fu微乳的优化处方为含药0.7%(w/v),0.05 mol·L-1 NaCl溶液50%,混合表面活性剂(AOT/Tween 85,Km=2)20%,油相29.3%。12 h累积透过量为(2 013.4±41.6)μg.cm-2,分别为0.7%药物水溶液和2.5%(w/w)市售乳膏(O/W)的20.23倍和10.38倍。该微乳具有一定的刺激性,但停药后可迅速恢复。NaCl的加入可显著增加W/O型微乳的含水量和载药量。NaCl/AOT-Tween 85/IPM微乳大大促进5-Fu的透过量,且皮肤刺激性小,可以作为5-Fu等水溶性差和透过能力差的药物的新型透皮给药载体。This study is to prepare the W/O microemulsion containing NaCl and fluorouracil（5-Fu） as a model drug to investigate the transdermal characteristics and skin irritation of the microemulsion in vitro.Isopropylmyristate（IPM） acting as oil phase,Aerosol-OT（AOT） as surfactant,Tween 85 as cosurfactant,NaCl solution was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring,and then 5-Fu powder was added.According to the area of microemulsion based 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 cells to study the influence of the amount of water and the drug loading capacity and optimize the formulation further.Refer to 5-Fu cream,the irritation of microemulsion on the rat skin was studied.The optimum formulation was composed of 0.7%（w/v） 5-Fu,50% NaCl solution（0.05 mol·L-1）,20% mix-surfactant（AOT/Tween 85,Km = 2） and 29.3% oil（IPM）.The cumulative amount of fluorouracil permeated in 12 h was（2 013.4 ± 41.6） μg·cm-2,20.23 folds and 10.38 folds more than 0.7% fluorouracil aqueous solution and 2.5%（w/w） fluorouracil cream,respectively.Microemulsion exhibited some irritation,but could be reversed after drug withdrawal.The addition of NaCl significantly increased the content of water and the drug loading in microemulsion systems.The NaCl/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：氯化钠 高载药量 氟尿嘧啶 W/O型微乳 透皮给药 

分 类 号：R943[医药卫生—药剂学]