Okamoto H, Hashida M, Sezaki H
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
J Pharm Sci. 1991 Jan;80(1):39-45. doi: 10.1002/jps.2600800111.
The percutaneous penetration-enhancing effects of 1-dodecyl- (azone), l-geranyl-, and 1-farnesylazacycloheptan-2-one were investigated using seven penetrants having a wide range of n-octanol-water partition coefficients. The penetration of the drugs from water vehicle (aqueous system) and ethanol vehicle (ethanolic system) through excised guinea pig skin was increased by pretreatment with the enhancers. Large enhancement was observed for the drugs, such as 5-fluorouracil and 6-mercaptopurine, with n-octanol-water partition coefficients of approximately unity. The penetration profiles were analyzed based on a one-layer skin model. Two parameters corresponding to the drug diffusivity and partitioning into the skin were obtained. In the aqueous system, the partitioning of drugs into the skin was increased by pretreatment with the enhancers. This led to an increase in drug penetration and accumulation in the skin; diffusivities were little affected. From these parameters, the drug amounts in the vehicle and the skin were well estimated for drugs having partition coefficients of less than 1. In the ethanolic system, the enhancement was far less than that observed in the aqueous system.
使用七种具有广泛正辛醇 - 水分配系数的渗透剂，研究了1 - 十二烷基 - （氮酮）、1 - 香叶基 - 和1 - 法呢基氮杂环庚烷 - 2 - 酮的经皮渗透增强作用。通过用增强剂预处理，药物从水载体（水性体系）和乙醇载体（乙醇体系）透过离体豚鼠皮肤的渗透增加。对于正辛醇 - 水分配系数约为1的药物，如5 - 氟尿嘧啶和6 - 巯基嘌呤，观察到了较大的增强作用。基于单层皮肤模型分析了渗透曲线。获得了与药物扩散率和在皮肤中的分配相对应的两个参数。在水性体系中，用增强剂预处理可增加药物向皮肤中的分配。这导致药物在皮肤中的渗透和积累增加；扩散率受影响较小。根据这些参数，对于分配系数小于1的药物，载体和皮肤中的药物量得到了很好的估计。在乙醇体系中，增强作用远小于在水性体系中观察到的增强作用。
