In vitro permeation of several drugs through the human nail plate: relationship between physicochemical properties and nail permeability of drugs.

The objectives of the present study are to clarify the relationship between the physicochemical properties and the nail permeability of drugs through human nail plates. Homologous p-hydroxybenzoic acid esters were used to investigate the relationship between the octanol/water partition coefficient and the permeability coefficient of several drugs. The nail permeability was found to be independent of the lipophilicity of a penetrating drug. However, the nail permeability of several model drugs was found to markedly decrease as their molecular weights increased. The nail permeability of an ionic drug was found to be significantly lower than that of a non-ionic drug, and the nail permeability of these drugs markedly decreased as their molecular weights increased. The permeation of a model drug, 5-fluorouracil (5-FU), through healthy nail plates was also determined and compared with that through nail plates with fungal infections. The drug permeation through a nail plate decreased with an increase in nail plate thickness. Nail plates with fungal infections exhibited approximately the same 5-FU permeation as healthy nail plates. We suggest that the permeability of a drug is mainly influenced by its molecular weight and permeability through nails with fungal infection can be estimated from data on healthy nail permeability.