Prediction of skin permeabilities of diclofenac and propranolol from theoretical partition coefficients determined from cohesion parameters.

The cohesion parameters of diclofenac and propranolol were determined experimentally. The theoretical partition coefficient (Ps,v) was calculated from the activity coefficient (gamma) and the cohesion parameters of the solvent (delta 1 = delta v), solute (delta 2), and skin (delta s). By using the extended Hildebrand solubility equation, the potential energy of solute-solvent interaction in a given solution was considered to have the gamma value derived from solubility data of diclofenac and propranolol in ethanol-aqueous buffer. Values for experimental permeability coefficients (Kp), which were determined from flux and solubility, were compared with values for the respective Ps,v. For a solvent that consists of ethanol-aqueous buffer exhibiting cohesion parameters in the range of delta v = 18-24 (cal/cm3)1/2, the fluxes increased and the Kp decreased because of the similarity in cohesion parameters of these solvents to the solute. The difference between Ps,v and experimental Kp suggests that ethanol in the solvent affects the membrane and diclofenac and propranolol penetrate through the membrane, possibly solvated by ethanol.