You Position: Home > Paper
Water in oil microemulsions containing NaCl for transdermal delivery of fluorouracil
( views:11, downloads:0 )
- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 6
- DOI:
- No doi available
- Key Word:
- 氯化钠;高载药量;氟尿嘧啶;W/O型微乳;透皮给药
Abstract： 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-1NaCl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.
- [1]M.J Hou,M Kim,D.O Shah.A light scattering study on the droplet size and interdroplet interaction in microemulsions of AOT-oil-water system[J].1988,123(2).
- [2]Patrick, A. I.,Beall, H. D.,Gilroy, P.,etc.Effect of vehicles on topical delivery of 5-fluorouracil (5FU) by 1-acyl-5FU prodrugs[J].1997,154(1).
- [3]H M, Pinedo,G F, Peters.Fluorouracil: biochemistry and pharmacology.[J].1988,6.
- [4]M.E. Leser,W.C. van Evert,W.G.M. Agterol.Phase behaviour of lecithinwateralcoholtriacylglycerol mixtures[J].1996,116(3).
- [5]刘芳,肖衍宇,平其能,等.以油包水型微乳为载体促进氟尿嘧啶的经皮渗透[J].2009,(5).
- [6]Moulik SP.,Paul BK..Structure, dynamics and transport properties of microemulsions [Review][J].1998,78(2).
- [7]Singh J,Singh RB,Singh BN.Effects of ionization and penetration enhancers on the transdermal delivery of 5-fluorouracil through excised human stratum corneum.[J].2005,298(1).
- [8]Paul BK,Mitra RK.Water solubilization capacity of mixed reverse micelles: Effect of surfactant component, the nature of the oil, and electrolyte concentration[J].2005,288(1).
- [9]Gao, S.,Singh, J..Effect of oleic acid/ethanol and oleic acid/propylene glycol on the in vitro percutaneous absorption of 5-fluorouracil and tamoxifen and the macroscopic barrier property of porcine epidermis[J].1998,165(1).
- [10]Roger Leung,Dinesh O Shah.Solubilization and phase equilibria of water-in-oil microemulsions: I. Effects of spontaneous curvature and elasticity of interfacial films[J].1987,120(2).
- [11]Wu H,Weiner ND,Ramachandran C,etc.Topical transport of hydrophilic compounds using water-in-oil nanoemulsions.[J].2001,220(1).
- [12]Mitra RK,Paul BK.Effect of NaCl and temperature on the water solubilization behavior of AOT/nonionics mixed reverse micellar systems stabilized in IPM oil[J].2005,255(1).
- [13]Roger Leung,Dinesh O Shah.Solubilization and phase equilibria of water-in-oil microemulsions: II. Effects of alcohols, oils, and salinity on single-chain surfactant systems[J].1987,120(2).