EFFECT OF VEHICLE ON THE SKIN PERMEABILITY OF DRUGS - POLYETHYLENE-GLYCOL 400-WATER AND ETHANOL-WATER BINARY SOLVENTS

A predictive method for skin permeability of drugs from polyethylene glycol 400 (PEG)-water and ethanol (EtOH)-water binary solvents is proposed. The method is based on a permeation model, in which the stratum corneum is assumed to be a membrane having two parallel permeation pathways: lipid and pore pathways. Skin permeability of several drugs with a variety of physicochemical properties from various PEG-water and EtOH-water solvents was tested. In PEG-water solvents, almost the same skin permeation rate of lipophilic drugs was obtained independent of the solvent, whereas the permeability coefficient of hydrophilic drugs decreased with increasing PEG fraction. The solvent viscosity was increased and the skin permeability of solvents was decreased by addition of PEG, suggesting the decreased diffusion of the drugs in the pore pathway. EtOH, in contrast, markedly enhanced the skin permeation rate of lipophilic drugs, though no such effect was found on hydrophilic drugs. The enhancing ratio in permeation of lipophilic drugs was dependent not on the lipophilicity of the drug but on the EtOH fraction in the solvent. EtOH-water solvents increased the fluidity of skin lipids, although the extraction of lipids by EtOH-water solvents was relatively low. These results suggest that EtOH enhances diffusion in the lipid pathway. Equations for predicting the skin permeability of a drug from various PEG-water and EtOH-water binary solvents were then derived. The skin permeation behavior of a drug can be predicted by its solubility in octanol and vehicle based on the parallel skin permeation pathway model.