氟尿嘧啶经皮给药微乳凝胶的研究  

Microemulsion-based gel of fluorouracil for transdermal delivery

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》2010年第11期1440-1446,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：制备氟尿嘧啶(5-Fu)微乳凝胶,考察影响微乳凝胶理化性质的因素,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水至油相中,形成空白微乳后直接加入凝胶剂和5-Fu,即形成5-Fu微乳凝胶。以黏度和电导率为指标,考察温度、明胶含量及微乳处方因素对微乳凝胶理化性质的影响。以单位面积的透皮累积渗透量(Qn)为指标,采用改进的Franz扩散池和离体小鼠皮肤研究明胶用量和载药量对离体鼠皮透皮吸收的影响,并考察微乳凝胶对大鼠皮肤的刺激性。水/AOT/Tween 85/IPM W/O型微乳系统,只有明胶作为凝胶剂才能形成微乳凝胶。在25℃、32℃及40℃时,形成微乳凝胶所需明胶含量分别为7%、14%及17%以上。微乳凝胶黏度随微乳中含水量的增加而减小,随表面活性剂用量的增加而减小,随Km值的增大而增大,不受药物加入的影响。微乳凝胶的电导率与微乳比较没有明显变化。载药量为0.5%,明胶含量为14%的微乳凝胶12 h体外透皮累积渗透量为(876.5±29.1)μg.cm?2,分别是0.5%含药水溶液的12.3倍,2.5%市售软膏制剂的4.5倍。微乳凝胶具有一定的刺激性,但停药后可迅速恢复。5-Fu微乳凝胶12 h累积渗透量优于市售软膏,且皮肤刺激性小,可以作为5-Fu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。This study is to prepare the microemulsion-based gel based on the W/O microemulsion and fluorouracil（5-Fu） as a model drug to study the transdermal characterization and observe its skin irritation of the microemulsion-based gel in vitro.IPM acted as oil phase,AOT as surfactant,Tween 85 as cosurfactant,water was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring,then 5-Fu powder was added.The gelatin was used as substrate to prepare 5-Fu microemulsion-based gel.The permeation flux of 5-Fu from 5-Fu microemulsion-based gel across excised mice skin was determined in vitro using Franz diffusion cell to study the influence of the amount of gelatin and the drug loading capacity.Refer to 5-Fu cream,the irritation of microemulsion and microemulsion-based gel on the rat skin was studied.Based on the water/AOT/Tween 85/IPM microemulsion,only the gelatin can form the microemulsion-based gel.At 25 ℃,32 ℃ and 40 ℃,the amount of gelatin required for the formation of microemulsion-based gel were 7%,14% and more than 17%,respectively.The 12 h transdermal cumulated permeation amount of 5-Fu from microemulsion-based gel containing 14% gelatin and 0.5% drug loading were（876.5 ± 29.1） μg.cm？2,12.3 folds and 4.5 folds more than 0.5% 5-Fu aqueous solution and 2.5%（w/w） 5-Fu cream,respectively.Microemulsion-based gel exhibited some irritation,but could be subsided after drug withdrawal.Microemulsion-based gel may be a promising vehicle for transdermal delivery of 5-Fu and other hydrophilic drug.

关 键 词：W/O型微乳 微乳凝胶 氟尿嘧啶 透皮给药 

分 类 号：R943[医药卫生—药剂学]