Which property best enables percutaneous diffusion?

• A. Both high water and lipid solubility
• B. Neither
• C. High lipid solubility only
• D. High water solubility only

Answer: (A)

Percutaneous diffusion relies on the drug moving through both lipophilic barrier regions and aqueous tissue environments. The outer skin layer, the stratum corneum, is lipid-rich, so the drug must partition into and diffuse through fats. At the same time, the underlying viable epidermis and dermis are more aqueous, so the drug also needs enough solubility in water to move through those spaces. A compound with both high water solubility and high lipid solubility can readily partition into the skin from a vehicle, traverse the lipid barrier, and then diffuse through the aqueous layers into systemic circulation. If a drug is only lipid-soluble, it may have trouble dissolving in the aqueous pathways; if it’s only water-soluble, it may not partition well into the lipid-rich stratum corneum. Therefore, having both properties makes percutaneous diffusion most efficient.