Hatanaka T, Inuma M, Sugibayashi K, Morimoto Y
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Chem Pharm Bull (Tokyo). 1990 Dec;38(12):3452-9. doi: 10.1248/cpb.38.3452.
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.
为了测定脂质和孔道（水性）途径对药物经皮总渗透的贡献，并建立药物稳态渗透速率的预测方法，将几种药物经离体无毛大鼠皮肤的渗透率与其某些理化性质之间的关系，分别与经聚二甲基硅氧烷（硅氧烷）和聚（甲基丙烯酸2-羟乙酯）（pHEMA）膜的情况进行了比较，这两种膜分别是典型的溶液扩散膜和多孔膜。发现药物在硅氧烷膜中的渗透系数与其正辛醇/水分配系数之间存在线性关系。对于pHEMA膜，渗透系数几乎与分配系数无关而保持恒定。另一方面，皮肤渗透特性可分为两类：一类涉及亲脂性药物，其渗透系数与分配系数相关，类似于硅氧烷膜；另一类涉及亲水性药物，其渗透系数几乎恒定，类似于pHEMA膜。根据上述结果，角质层作为皮肤中的主要屏障，可被描述为具有两条平行渗透途径的膜：脂质途径和孔道途径。基于该皮肤渗透模型推导了预测药物稳态渗透速率的方程。
