不同接受液和动物皮肤对格列美脲体外经皮渗透行为的影响

The Effect of Different Permeation Receptors and Various Exercised Animal Skin on the Percutaneous Permeability of Glimepiride in vitro

建立格列美脲体外透皮吸收的HPLC分析方法,采用改良Franz双室渗透扩散装置,以累积渗透量、透皮速率常数和透皮时滞为评价指标,研究了5种透皮吸收接受液和6种实验动物皮肤对格列美脲体外经皮渗透行为的影响。结果表明:①所建立的HPLC方法在0 1～30μg·mL-1间线性良好,高中低质量浓度样品的日内和日间相对标准偏差RSD均小于3%,最低检测质量浓度5 55ng·mL-1,最低检测限0 28ng;②与其它接受液—生理盐水、乙醇 生理盐水、PEG400 生理盐水和pH7 4磷酸盐缓冲液相比,乙醇 PEG400 生理盐水具有最大的透皮速率常数和最短的透皮时滞;③在大鼠、小鼠、裸鼠、豚鼠、猫和新西兰大白兔等动物皮肤中,裸鼠的透皮速率常数最大,豚鼠最小;裸鼠的透皮时滞最短,小鼠最长。另外,在猫皮作为透皮实验皮肤的特性中,发现猫皮透皮速率较小,透皮时滞却较短。提示在格列美脲的体外透皮实验中,采用乙醇PEG400 生理盐水作接受液,裸鼠皮肤作实验皮肤,可获得最大的透皮速率常数和最短的透皮时滞。

RP-HPLC method of glimepiride in different permeation receptors was established in this article. Using improved Franz-type two-chamber diffusion cell, the in vitro permeation test of glimepiride ethanol solution via 5 kinds of isolated animal skin and in 6 kinds of permeation receptors was respectively carried out by adopting cumulative permeation quantity (Q), stability permeation rate(J) and permeation lagged time (t-(lag)) as permeability index. The results showed that: ① In this HPLC method, the glimepiride concentration in different permeation receptors was linear over the range of 0.1～30 μg·mL^(-1) and the RSD inter-day and intra-day were both less than 3%. The minimal detectable concentration and amount were 5.55 ng·mL^(-1) and 0.28 ng respectively. ② Compared with other permeation receptors-saline, EtOH/saline, PEG400/saline and pH 7.4 phosphate buffer, EtOH/PEG400/saline (5∶2∶3,V/V) had the largest J and the shortest t-(lag). ③ Among the animal skin exercised from rat, mouse, hairless mouse, guinea pig, rabbit and cat, hairless mouse skin had the largest J whereas the guinea pig had the smallest; the t-(lag) of hairless mouse skin was the shortest but that of mouse was the longest. Furthermore, the cat skin was first reported as permeation skin. Although the stability permeation rate of the cat skin was almost the same small as that of the guinea pig, its permeation lagged time was the same short as that of the hairless mouse. It suggested that when glimepiride permeated through hairless mouse skin in vitro and in the EtOH/PEG400/saline permeation receptor, it had the largest J and the shortest t-(lag).