Nitroglycerin (TNG) transdermal drug delivery systems (TDDSs) with different acrylic pressure-sensitive adhesives (PSAs) and chemical permeation enhancers (CPEs) were prepared. The effects of PSAs and CPEs types and concentrations on skin permeation and in vitro drug release from devices were evaluated using the dissolution method as well as the modified-jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that the permeation rate or steady state flux ( ) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak 2516 and Duro-Tak 2054 showed the highest and Duro-Tak 2051 showed the lowest . Among the various CPEs, propylene glycol and cetyl alcohol showed the highest and the lowest enhancement of the skin permeation of TNG, respectively. The adhesion properties of devices such as 180° peel strength and probe tack values were obtained. It was shown that increasing the concentration of CPE led to reduction in the adhesion property of PSA. Moreover, after optimization of the formulation, it was found that the use of 10% PG as a CPE and 25% nitroglycerin loading in Duro-Tak 2054 is an effective monolithic DIAP for the development of a transdermal therapeutic system for nitroglycerin. 1. Introduction Nitroglycerin (1,2,3-propanetriol trinitrate) (TNG) is a vasodilator that has been widely used for the treatment of angina pectoris. For the acute treatment of angina, it is available as chewing capsules, sublingual tablets, and mouth spray. Injection solutions are available for the treatment of acute myocardial infarction. It decreases the smooth muscle tonus of blood vessels through the local production of nitrous oxide (NO). Because of its lipophilic nature, it is rapidly absorbed and extensively distributed when administrated orally, and afterwards it is excreted by the renal route. TNG is rapidly metabolized in the liver (half-life of 1 to 4？min) by hepatic enzymes to dinitrates and mononitrates and undergoes a massive hepatic first pass effect [1, 2]. Therefore, its bioavailability (BA) is below 1%. To bypass this first pass effect and improve the low bioavailability of TNG, the sublingual, intravenous, and transdermal administrations of TNG are possible solutions to overcome these problems. The sublingual bioavailability (38%) is still low, while the intravenous administration bioavailability is high enough, but it is an invasive procedure and it is mostly useful for the most acute infarction. Therefore, the
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