Penetration of adenosine into excised human skin from binary vehicles: the enhancement factor

Human skin samples are permeable to adenosine delivered from 0.5-3% solutions in vehicles consisting of propionic acid, hexanoic acid, or mixtures of these in various ratios. The observed optimal Kp, hence flux, of adenosine from the binary vehicles is 0.4 X 10(-3) cm/min, while that from propionic acid is 0.12 X 10(-3), and that from hexanoic acid is 0.16 X 10(-3) cm/min. The bell-shaped dependence of the observed Kp on donor vehicle composition may be resolved into two trends proceeding in opposite directions: an increase in the excess free energy of adenosine in the donor vehicle with an increase in volume fraction of hexanoic acid in that vehicle ("push" effect); and an increase in the flux of adenosine with an increase in the flux of propionic acid ("pull" effect) delivered from the binary vehicle. The Kp of adenosine anticipated from its excess free energy in the donor phase ("push" effect), independent of any enhancing effect due to the presence of propionic acid, is calculated from the partial molal volume of adenosine in a given vehicle; this volume correlates inversely with the solubility parameter of that vehicle. The ratio of the observed Kp to the calculated Kp gives an enhancement factor which is approximately 6 for a formulation consisting of four volumes of hexanoic acid and six volumes of propionic acid. A similar trend is found for binary vehicles of isopropyl myristate and propionic acid.