Principles of Transepidermal Penetration and Vehicle Selection

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Fick Diffusion Kinetics in the Skin Barrier

The mass transfer of an active ingredient across the epidermal biological membrane is mathematically governed by Fick's first law of diffusion:

J = (K · D · Δ C)/(h)

Where J represents the net flux of the drug through the skin, K is the partition coefficient of the solute between the vehicle and the stratum corneum (an index of its lipophilicity), D is the diffusion coefficient of the drug within the lipid matrix, Δ C is the concentration gradient of the active substance across the barrier, and h is the effective thickness of the diffusion path (the thickness of the stratum corneum).

The selection of the vehicle determines the release and penetration rate of the drug by altering K and hydration of the stratum corneum. The most occlusive vehicles (lipophilic ointments and ointments) reduce the transepidermal evaporation of water, increasing the degree of hydration of the stratum corneum and, therefore, the D value. In contrast, hydrophilic lotions and gels facilitate the evaporation of free water, being ideal for acute exudative lesions or hairy areas, but with less capacity for deep penetration.