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

The permeability coefficient, Kp, of pure unbranched alkanoic acids (C2-C7) applied to isolated porcine skin, reached a maximum in the solubility parameter (delta 2) range of 9.7-10 cal1 /2/cm3/2. When these and other penetrants were delivered from a solvent vehicle, the following linear relationships could be demonstrated: (a) between log Kp and the molar attraction constant of the penetrant [delta 2v2 or (-Ev)1/2] for six unbranched and six branched acids delivered from 1 M solution in n-heptane; (b) between Kp and the partial molal volume difference in n-heptane (-v2-v02) for the unbranched acids; and (c) between Kp and (-v2-v02) for propionic acid delivered from 1 M solutions in nine solvents having delta 1 values in the range 7.4-12.7 cal1 /2/cm3/2. Drug penetrability in a given series could be assessed from knowledge of the excess free energy of the penetrant in the delivery system used.