Principles of transdermal nitroglycerin administration.

The currently marketed delivery systems for transdermal nitroglycerin (GTN) develop fairly constant GTN plasma concentrations throughout the 24-h application period. This may be associated with tolerance, particularly when higher doses are employed. Because of this problem, a new GTN transdermal delivery system (TDS) has been developed which provides a time-dependent, non-constant drug delivery rate. This system was engineered to provide high GTN plasma concentrations during the first 12h of application which should prevent exercise-induced angina and low nitroglycerin levels during the second 12-h period to prevent tolerance. This GTN TDS with a phasic release profile is described and the in vitro and in vivo release rates and resulting plasma concentrations are contrasted with those of conventional GTN transdermal patches.