Roy S D, Fujiki J, Fleitman J S
Syntex Research, Palo Alto, CA 94304.
J Pharm Sci. 1993 Dec;82(12):1266-8. doi: 10.1002/jps.2600821217.
The in vitro permeabilities of alkyl p-aminobenzoates through living skin equivalent (LSE) and cadaver skin were compared. Methyl, ethyl, and butyl p-aminobenzoates were used as model compounds. The permeabilities of these compounds through LSE and cadaver skin from an aqueous drug suspension were determined with a flow-through diffusion cell. The permeability coefficients of these esters in LSE were an order of magnitude higher than in cadaver skin. This was primarily because of low resistances offered by the outermost layer (i.e., stratum corneum) of LSE. In the case of cadaver skin, the permeability coefficient increased as the carbon chain length increased, whereas no appreciable change in the permeability coefficients of these esters in LSE was observed. These results clearly suggest that the LSE membrane offered very little resistance as opposed to cadaver skin. Therefore, the LSE membrane may not quantitatively represent a good human skin model for evaluating skin permeation of a drug from topical or transdermal formulations.
比较了对氨基苯甲酸烷基酯透过活性皮肤替代物(LSE)和尸体皮肤的体外渗透性。以对氨基苯甲酸甲酯、乙酯和丁酯作为模型化合物。使用流通扩散池测定这些化合物从水性药物悬浮液透过LSE和尸体皮肤的渗透性。这些酯类在LSE中的渗透系数比在尸体皮肤中的高一个数量级。这主要是因为LSE最外层(即角质层)提供的阻力较低。对于尸体皮肤,渗透系数随着碳链长度的增加而增加,而在LSE中未观察到这些酯类渗透系数有明显变化。这些结果清楚地表明,与尸体皮肤相比,LSE膜提供的阻力非常小。因此,LSE膜可能无法定量地代表用于评估局部或透皮制剂中药物皮肤渗透的良好人体皮肤模型。