Kinetic analysis of transdermal nitroglycerin delivery.

The current success of transdermal nitroglycerin delivery systems has focussed much attention upon the skin as a portal of drug entry into the systemic circulation. Although there are multiple potential problems associated with this administration route to elicit central effects, considerable efforts are being made to identify transdermal drug delivery candidates and to determine whether a sufficient percutaneous input rate can be achieved such that therapeutic levels in the biophase may be maintained. The purpose of this work is to develop a physically-based kinetic model of percutaneous absorption, which includes delivery system input. Both zero-order and first-order situations are considered and the model is employed to analyze nitroglycerin plasma concentration vs. time data following transdermal delivery both from a controlled-release patch and from an ointment. The kinetic model includes rate parameters which relate to drug transport across the stratum corneum, to further diffusion across the viable epidermis and to the competition for substrate between these two layers of skin tissue. We show how these kinetic constants may be determined physicochemically and used, in conjunction with designated (delivery system) input rates and established systemic elimination kinetics, to predict plasma concentrations as a function of time. The agreement with human in vivo data for nitroglycerin, delivered from either a patch or a more conventional vehicle, is good and suggests that the simulation proposed may enable facile estimation of the feasibility of transdermal drug delivery.