Liu P, Bergstrom T K
Pharmaceuticals Division, CIBA-GEIGY Corporation, Suffern, NY 10901, USA.
J Pharm Sci. 1996 Mar;85(3):320-5. doi: 10.1021/js9502783.
This paper demonstrates the usefulness of an equilibria-cotransport model for understanding the isopropyl alcohol-enhanced transport of an ionizable model compound, terbutaline in its sulfate salt form, through human skin in vitro. With the same isopropyl alcohol concentrations (0 - 80% v/v) present at both sides of skin, the permeation experiments were conducted using split-thickness skin and dermis membranes. The equilibria-cotransport model was consistent with total terbutaline flux and a terbutaline-to-sulfate flux ratio, both increased with increasing isopropyl alcohol and/or terbutaline sulfate concentrations. From the saturated drug solutions, aqueous isopropyl alcohol enhanced terbutaline skin flux about 10 - 100-fold with the maximum at 60 - 80% isopropyl alcohol. This overall flux enhancement was qualitatively separated into the contributions of isopropyl alcohol effects on both equilibrated donor concentrations and skin permeabilities of protonated terbutaline, terbutaline-sulfate ion pair anion, and neutral terbutaline-sulfate (2:1) ion triplet. In addition to altering the species equilibria, isopropyl alcohol was found to enhance the transport of both neutral and ionic species of terbutaline sulfate across stratum corneum.
本文证明了一种平衡-共转运模型对于理解硫酸特布他林（一种可电离的模型化合物）在异丙醇增强下通过人皮肤的体外转运的有用性。在皮肤两侧存在相同异丙醇浓度（0 - 80% v/v）的情况下，使用分层皮肤和真皮膜进行渗透实验。平衡-共转运模型与总特布他林通量以及特布他林与硫酸盐通量之比一致，二者均随异丙醇和/或硫酸特布他林浓度的增加而增加。从饱和药物溶液来看，异丙醇水溶液可使特布他林的皮肤通量提高约10 - 100倍，在异丙醇浓度为60 - 80%时达到最大值。这种整体通量的增强在性质上可分为异丙醇对质子化特布他林、硫酸特布他林离子对阴离子以及中性硫酸特布他林（2:1）离子三联体的平衡供体浓度和皮肤渗透率的影响。除了改变物种平衡外，还发现异丙醇可增强硫酸特布他林的中性和离子物种跨角质层的转运。
