Pharmaceutical considerations of transdermal nitroglycerin delivery: the various approaches.

When formulated as a sublingual or an oral sustained-release dosage form, nitroglycerin has certain shortcomings, i.e., decreased duration of antianginal action and extensive hepatic first-pass elimination, which limit its efficacy. The finding that administration of nitroglycerin in the form of topical ointment decreases the extent of hepatic first-pass elimination and increases the duration of therapeutic activity has pointed the way to the possibility of developing a more effective transdermal drug delivery device. Three such devices are the Nitrodisc , Nitro-Dur, and Transderm -Nitro systems. All three systems generate effective plasma drug levels within 30 minutes and maintain steady-state drug plasma levels as follows: the 16 cm2 Nitrodisc at 280.6 +/- 18.7 pg/ml for 32 hours; the 20 cm2 Nitro-Dur at 201.4 +/- 60.7 pg/ml for 24 hours; and the 20 cm2 Transderm -Nitro system at 209.8 +/- 22.8 pg/ml for 24 hours. In vitro studies show that the drug penetrates the skin with zero-order kinetics in all three systems, the rate for Nitrodisc being 20% greater than that of the other systems. When the daily nitroglycerin dose is calculated in terms of skin permeation rate and the device's surface area, the three transdermal systems become clinically interchangeable.