Explaining skin permeation of 2-butoxyethanol from neat and aqueous solutions.

Absorption of 2-butoxyethanol (BE) from neat and aqueous solutions of BE was measured through rat skin in vitro and in vivo and through silicone membranes. Like previous studies in human and guinea pig skin, BE flux increased proportional to BE concentration only when the weight fraction of BE (w(BE))<about 0.2. The flux of BE was relatively constant for 0.2<w(BE)<0.8, and it decreased dramatically for w(BE)>0.8. Experimental values of thermodynamic activity for BE and water in aqueous solutions of BE are presented. Except when the water content in the vehicle is small, skin is fully hydrated and the flux of a BE through it is proportional to the thermodynamic activity of BE. When w(BE)>0.8, there is a sharp drop in the activity-normalized BE flux through skin, which coincides with a decrease in water activity from 0.9 at w(BE)=0.8 to zero for neat BE. These observations are consistent with reduced BE flux arising from skin dehydration. From an analysis of previously published data, the activity-normalized flux of BE through hydrated human skin was determined to be 2-4 mg cm(-2)h(-1), which is in reasonable agreement with predictions of its maximum flux.