Percutaneous absorption of alkanoic acids II: Application of regular solution theory

The permeability coefficient, K_p, of pure unbranched alkanoic acids (C₂‐C₇) applied to isolated porcine skin, reached a maximum in the solubility parameter (δ₂) range of 9.7–10 cal^1/2/cm^3/2. When these and other penetrants were delivered from a solvent vehicle, the following linear relationships could be demonstrated: (a) between log K_p and the molar attraction constant of the penetrant [δ₂^v₂ or (‐Ev)^1/2] for six unbranched and six branched acids delivered from 1 M solution in n‐heptane; (b) between K_p and the partial molal volume difference in n‐heptane (ν₂ ‐ v 20) for the unbranched acids; and (c) between K_p and (ν₂ ‐ v 20) for propionic acid delivered from 1 M solutions in nine solvents having δ₁ values in the range 7.4–12.7 cal^1/2/cm^3/2. Drug penetrability in a given series could be assessed from knowledge of the excess free energy of the penetrant in the delivery system used.