Rosado Catarina, Cross Sheree E, Pugh W John, Roberts Michael S, Hadgraft Jonathan
Skin Research Centre, Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3XF, United Kingdom.
Pharm Res. 2003 Sep;20(9):1502-7. doi: 10.1023/a:1025778731901.
The flux of a topically applied drug depends on the activity in the skin and the interaction between the vehicle and skin. Permeation of vehicle into the skin can alter the activity of drug and the properties of the skin barrier. The aim of this in vitro study was to separate and quantify these effects.
The flux of four radiolabeled permeants (water, phenol, diflunisal, and diazepam) with log Koct/water values from 1.4 to 4.3 was measured over 4 h through heat-separated human epidermis pretreated for 30 min with vehicles having Hildebrand solubility parameters from 7.9 to 23.4 (cal/cm3)1/2.
Enhancement was greatest after pretreatment with the more lipophilic vehicles. A synergistic enhancement was observed using binary mixtures. The flux of diazepam was not enhanced to the same extent as the other permeants, possibly because its partitioning into the epidermis is close to optimal (log Koct 2.96).
An analysis of the permeant remaining in the epidermis revealed that the enhancement can be the result of either increased partitioning of permeant into the epidermis or an increasing diffusivity of permeants through the epidermis.
局部应用药物的通量取决于其在皮肤中的活性以及载体与皮肤之间的相互作用。载体渗透进入皮肤会改变药物的活性和皮肤屏障的特性。本体外研究的目的是分离并量化这些效应。
通过热分离的人表皮，对log Koct/水值在1.4至4.3之间的四种放射性标记渗透剂（水、苯酚、二氟尼柳和地西泮）的通量进行了4小时的测量，这些表皮预先用希尔德布兰德溶解度参数在7.9至23.4（cal/cm3）1/2之间的载体处理30分钟。
用亲脂性更强的载体预处理后增强作用最大。使用二元混合物观察到协同增强作用。地西泮的通量增强程度不如其他渗透剂，可能是因为其在表皮中的分配接近最佳值（log Koct 2.96）。
对表皮中残留渗透剂的分析表明，增强作用可能是由于渗透剂在表皮中的分配增加，或者是渗透剂通过表皮的扩散率增加所致。
