【摘要】 目的:对氟尿嘧啶的理化性质进行研究,并考察促渗剂对氟尿嘧啶透皮吸收的影响,为氟尿嘧啶经皮给药剂型的设计提供理论依据。方法:考察温度、光照及pH对氟尿嘧啶稳定性的影响;测定氟尿嘧啶在水、不同pH磷酸盐缓冲液以及多种油和表面活性剂中的溶解度;采取改进的Franz扩散池和离体小鼠皮肤研究氟尿嘧啶在不同pH环境下以及添加促渗剂后对离体鼠皮透皮吸收的影响。结果:在4℃、25℃、32℃、60℃条件下,在pH5.0、pH7.4、pH8.0磷酸盐缓冲液中,在光照条件(4 500 Lx)下,氟尿嘧啶均能稳定存在。氟尿嘧啶在水及不同pH磷酸盐缓冲液中的溶解度均大于在油和表面活性剂中的溶解度。氟尿嘧啶在水和不同pH磷酸盐缓冲液中的体外经皮释放均符合零级释放。含不同促渗剂的氟尿嘧啶的透皮速率及累积渗透量有明显差别,其促进强度依次为桉叶油>薄荷油>氮酮>H二乙二醇单乙基醚H>N-甲基-2-吡咯烷酮。结论:氟尿嘧啶不受温度、光照、pH值的影响;制成经皮给药制剂时,桉叶油的加入对氟尿嘧啶的促渗作用最大。更多还原

【Abstract】 OBJECTIVE: To study physicochemical of fluorouracil( 5- Fu) and percutaneous effect of transdermal enhancers upon transdermal absorption of 5- Fu through mice skin. METHODS The physicochemical properties in vitro including stability under the condition of illumination,different temperatures and pH and solubility in water,different pH phosphate buffers,oil or surface were determined. The permeation flux of 5- Fu across excised mice skin was determined in vitro using Franz diffusion cell to study the influence of different pH phosphate buffers and the addition of transdermal enhancers. RESULTS The 5- Fu could be stable under the condition of illumination( 4500 Lx),4 ℃,25 ℃,32℃,60 ℃ and pH 5.0,pH 7.4,pH 8.0 phosphate buffers. The solubility of 5-Fu in water and different pH phosphate buffers were greater than that in oil or surfactant. The percutaneous absorption of 5- Fu in water and different pH phosphate buffers in vitro were zero order releasing kinetics. Several enhancers exhibited different effects,the order of effect was eucalyptus oil > peppermint > azone > transcutol P > NMP,CONCLUSIONS 5- Fu was made for W / O microemulsion and eucalyptus oil was the most effective one.更多还原