接受液中的乙醇浓度对药物体外透皮试验的影响

Effect of ethanol concentration in receiver fluid on in vitro transdermal test

该文考查接受液中不同浓度乙醇对药物体外透皮试验的影响。通过配制不同浓度乙醇-生理盐水作为接受液,供给池不加药,大鼠皮肤按正常操作条件处理12 h,然后用生理盐水置换出含醇生理盐水,加药测定药物透皮吸收过程,并计算相关透皮参数;利用扫描电镜观察离体大鼠皮肤在经含醇生理盐水作接受液处理12 h后皮肤角质层的形态变化。结果表明,10%,15%乙醇-生理盐水未影响相关药物透皮参数,但20%乙醇-生理盐水组药物稳态透皮速率及滞后时间有显著变化,并随着乙醇浓度的增加影响增大,50%乙醇组透皮速率甚至为对照组的10倍。扫描电镜结果显示,当乙醇用量超过20%时,正常皮肤表面的褶皱逐渐消失,并伴有脱落的鳞片状物,毛囊口扩展。因此,大鼠皮肤的体外透皮试验中,接受液中乙醇用量超过20%时,将影响皮肤正常生理结构从而改变其屏障特性,因此接受液中的乙醇浓度应控制在20%以下。

The present paper was designed to investigate the effect of varying concentrations of ethanol in receiver solution on the in vitro transdermal permeation of drug across the rat skin. 5-fluorouracil （5-FU） was used as the model drug on account of its good hydrophility, the excised rat skins were treated with different concentration ethanol prepared with normal saline for 12 h, then replaced by normal saline and added the saturated model drug into the donor compartment to determine the transdermal parameters of the drug. Meanwhile, scanning electron microscopy （SEM） was employed to monitor the effect of the different concentration ethanol on the stra- tum corneum of the rat skin. The ethanol below the concentration of 15% didn＇t significantly affect the barrier profile of the rat skin, while significant difference of in steady-state transdermal rate and lag times were observed when the concentration of ethanol was 20% or above. The SEM studies indicated that wrinkle of the intact rat skin gradually disappeared and a number of flakes were desquamated from the skin when the concentration of ethanol was above 20%. The results showed that the low concentration of the ethanol （ below 15% ） didn＇t obviously affect the excised skin, yet the barrier profile of rat skin would significantly disrupted with the concentration of ethanol above 20%.