PREDICTION OF SKIN PERMEABILITY OF DRUGS .1. COMPARISON WITH ARTIFICIAL MEMBRANE
PREDICTION OF SKIN PERMEABILITY OF DRUGS .1. COMPARISON WITH ARTIFICIAL MEMBRANE
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DOI：
10.1248/cpb.38.3452
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发表时间：
1990-12-01
影响因子：
1.7
通讯作者：
MORIMOTO, Y
中科院分区：
文献类型：
--
作者：
HATANAKA, T;INUMA, M;MORIMOTO, Y
为了测量脂质和孔隙（水）途径对药物总皮肤渗透的贡献，并建立药物稳态渗透速率的预测方法，比较了几种药物在离体无毛大鼠皮肤中的渗透性与某些物理化学性质的关系。通过聚二甲基硅氧烷的渗透性（有机硅）和聚（甲基丙烯酸2-羟乙酯）（pHEMA）膜，分别作为典型的溶液扩散膜和多孔膜。药物对硅胶膜的渗透系数与正辛醇/水分配系数呈线性关系。对于pHEMA膜，渗透系数几乎是恒定的分配系数无关。另一方面，皮肤渗透性质可分为两类：一类涉及亲脂性药物的情况，其中渗透系数与分配系数相关，类似于硅胶膜;另一类涉及亲水性药物，其中渗透系数几乎恒定，类似于pHEMA膜。从以上结果，角质层，皮肤中的主要屏障，可以被描述为具有两个平行的渗透途径的膜：脂质途径和孔途径。基于该模型，推导出药物稳态渗透速率的预测方程。
In order to measure the contribution of lipid and pore (aqueous) pathways to the total skin permeation of drugs, and to establish a predictive method for the steady state permeation rate of drugs, the relationship between permeability through excised hairless rat skin and some physicochemical properties of several drugs were compared with those through polydimethylsiloxane (silicone) and poly(2-hydroxyethyl methacrylate) (pHEMA) membranes, as typical solution-diffusion and porous membranes, respectively. A linear relationship was found between the permeability coefficients of drugs for the silicone membrane and their octanol/water partition coefficients. For the pHEMA membrane, the permeability coefficients were almost constant independent of the partition coefficient. On the other hand, the skin permeation properties could be classified into two types: one involves the case of lipophilic drugs, where the permeability coefficient is correlated to the partition coefficient, similar to the silicone membrane; and the other involves hydrophilic drugs, where the permeability coefficients were almost constant, similar to pHEMA membrane. From the above results, the stratum corneum, the main barrier in skin, could be described as a membrane having two parallel permeation pathways: lipid and pore pathways. An equation for predicting the steady state permeation rate of drugs was derived based on this skin permeation model.