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In vitro techniques were used to test certain concepts regarding the enhancement of the transdermal delivery of nifedipine from topical vehicles. Tested vehicles include the volatile solvent acetone, nonvolatile solvents such as propylene glycol and isopropyl myristate, volatile/nonvolatile mixtures, and those mixtures with a polymer additive. An ethylene-vinyl acetate (EVA) copolymer membrane was used as the lipoidal barrier for the diffusing drug. Not merely the rate of transport per unit area, but the activity coefficient and the diffusion coefficient of the penetrating agent in the barrier were obtained. Despite the 10,000-fold difference in the vehicle concentration, water and several hydrophilic vehicles containing finely ground suspensions of the drug produced nearly the same rate of penetration. Some lipophilic solvents affected the barrier function of the EVA membrane to promote penetration of the drug. It has been found that the activity coefficient in the EVA membrane is very susceptible to wide variations by imbibition of such solvents. From volatile/nonvolatile mixtures, a transient enhancement in the transport of nifedipine across the membrane was observed. The increase in the flux was accounted for by the increase in the thermodynamic activity of the drug in the nonvolatile vehicle caused by the evaporation of the volatile component. The eventual decrease in penetration was the result of the drug precipitation from the supersaturated solution. The precipitation was inhibited and/or retarded during the entire time course of the experiments when a polymer additive was present. The steady-state fluxes from mixtures with a polymer additive were higher by about 3 to 5 times than that of the control experiment.

journal of pharmacobio-dynamics

Enhancement of transdermal delivery by superfluous thermodynamic potential. I. Thermodynamic analysis of nifedipine transport across the lipoidal barrier.