Yoneto K, Ghanem A H, Higuchi W I, Peck K D, Li S K
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake 84112, USA.
J Pharm Sci. 1995 Mar;84(3):312-7. doi: 10.1002/jps.2600840310.
The influences of 1-ethyl-, 1-butyl-, 1-hexyl-, and 1-octyl-2-pyrrolidone in their saline solutions on the transport of beta-estradiol, corticosterone, and hydrocortisone across hairless mouse skin under in vitro conditions have been investigated by the physical model approach. The experimental data were interpreted with a physical model that treats the stratum corneum as a diffusional barrier with a lipoidal pathway and a pore pathway. Enhancement factors (E values) for the lipoidal pathway were calculated from the permeability coefficients and solubility data as a function of the 1-alkyl-2-pyrrolidone concentration for all three permeants. A pattern of increasing E values with increasing 1-alkyl-2-pyrrolidone chain length was found, and the results were essentially the same for all three steroidal permeants. A nearly semilogarithmic linear relationship was also obtained between the enhancement potency and the carbon number of the alkyl chain; there was about an approximately 3.5-fold increase in the enhancement potency per 1-alkyl-2-pyrrolidone methylene group. An important outcome of this research is that the enhancement potencies of the 1-alkyl-2-pyrrolidones were essentially the same as those for the previously studied n-alkanols when compared at the same carbon numbers of the alkyl groups. This result is somewhat surprising as it suggests that the enhancer action resides (in its entirety) in the alkyl group, and the nature of the polar head group may not be intrinsically important in transdermal enhancement of the lipoidal pathway within a class of permeation enhancers.
采用物理模型方法，研究了1 - 乙基 - 、1 - 丁基 - 、1 - 己基 - 和1 - 辛基 - 2 - 吡咯烷酮在其盐溶液中对β - 雌二醇、皮质酮和氢化可的松在体外条件下透过无毛小鼠皮肤的影响。实验数据用一个物理模型进行解释，该模型将角质层视为具有脂质途径和孔隙途径的扩散屏障。根据渗透率系数和溶解度数据，计算了所有三种渗透物在脂质途径中的增强因子（E值），作为1 - 烷基 - 2 - 吡咯烷酮浓度的函数。发现随着1 - 烷基 - 2 - 吡咯烷酮链长增加，E值呈增加趋势，并且对于所有三种甾体渗透物，结果基本相同。在增强效力和烷基链的碳原子数之间也获得了近似半对数线性关系；每增加一个1 - 烷基 - 2 - 吡咯烷酮亚甲基，增强效力大约增加3.5倍。该研究的一个重要结果是，当在相同烷基碳原子数下进行比较时，1 - 烷基 - 2 - 吡咯烷酮的增强效力与先前研究的正构烷醇基本相同。这一结果有些令人惊讶，因为它表明增强作用（完全）存在于烷基中，并且在一类渗透增强剂中，极性头部基团的性质对于脂质途径的透皮增强可能本质上并不重要。
