氟尿嘧啶经皮给药微乳凝胶的研究-药学学报.doc

氟尿嘧啶经皮给药微乳凝胶的研究 肖衍宇1, 刘 芳1, 陈志鹏2, 平其能1* (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) 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25 ℃、32 ℃及40 ℃时, 形成微乳凝胶所需明胶分别为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。 关键词: W/O型微乳; 微乳凝胶; 氟尿嘧啶; 透皮给药 A 文章编号: 0513-4870 (2010) 11-1440-07 Microemulsion-based gel of fluorouracil for transdermal delivery XIAO Yan-yu1, LIU Fang1, CHEN Zhi-peng2, PING Qi-neng1* (1. Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China; 2. Department of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, China) ( Abstract: 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