Percutaneous penetration enhancement and its quantification.

True penetration enhancing effects resulting from structural alterations of the barrier stratum corneum manifest themselves in an increase of the drug diffusion coefficient DB and/or of the drug solubility in the barrier csB. The quantification of enhancing effects on drug penetration is possible either by the direct determination of the drug fluxes or by an indirect determination through the measurement of the pharmacodynamic response. In both cases the thermodynamic drug activity has to be considered. In the case of pharmacodynamic measurements, enhancing effects may be determined from the horizontal distance of activity-response lines obtained without and with enhancer, respectively, i.e. the quotient of the drug concentrations that induce the same effect. The activity-standardized bioavailability factors fa obtained from the horizontal distances correspond to the enhancer-induced relative changes in the permeabilities PB, or more exactly in the product DB X csB. On the other hand, the vertical distance between the activity-response lines, i.e. the differences in the drug response after application of preparations with equal (even maximum) thermodynamic drug activities may be used to quantify penetration enhancing effects.