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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。
Fluorouracil (5-Fu) W / O microemulsion with high water content, high drug loading capacity and high permeability was prepared by adding sodium chloride electrolyte (NaCl), and its in vitro dermal penetration and skin irritation . Using isopropyl myristate (IPM) as oil phase, dioctyl sodium sulfosuccinate (AOT) as surfactant and Tween 85 as cosurfactant, NaCl solution was added dropwise to the solution by magnetic stirring at room temperature In the oil phase, 5-Fu powder is added directly after the formation of the blank microemulsion to form a 5-Fu microemulsion. Based on the pseudo-ternary phase diagram, the transdermal cumulative permeation per unit area (Qn) was used as an index. The modified Franz diffusion cell and the skin of the isolated mice were used to investigate the effect of water content and drug loading in the microemulsion prescription. Skin through the impact of the amount of optimization of prescription. The physico-chemical properties of NaCl / AOT-Tween 85 / IPM microemulsion were studied with surface tension, viscosity and conductivity as indexes. The skin irritation of the optimal prescription was preliminarily evaluated. The results showed that the optimal formulation of 5-Fu microemulsion was as follows: 0.7% (w / v) of drug, 50% of 0.05 mol·L-1 NaCl solution, 20% of mixed surfactant (AOT / Tween 85, Oil phase 29.3%. The cumulative permeation at 12 h was (20.33 ± 41.6) μg.cm-2, which was 20.23-fold and 10.38-fold higher than the 0.7% aqueous drug solution and 2.5% (w / w) commercial cream (O / W), respectively. The microemulsion has some irritation, but can be quickly restored after stopping. NaCl addition can significantly increase the W / O microemulsion water content and drug loading. NaCl / AOT-Tween 85 / IPM microemulsion greatly promotes 5-Fu permeation and has low skin irritation, and can be used as a novel transdermal drug delivery carrier such as 5-Fu with poor water solubility and poor permeability.