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The aim of this work was to investigate the correlation of permeation behavior of transdermal formulations through a novel synthetic membrane (Strat-M® EMD Millipore, MA) and human cadaver skin. Strat-M® membranes were designed with the intent to share similar structural and chemical characteristics found in the human skin however, omitting any biological behavior due to the absence of viable cells. Both human skin and the membrane display a layered structure with a very tight top layer. Additionally, the Strat-M® membrane contains a combination of lipids in a specific ratio similar to what is found in the human stratum corneum (SC). Formulations containing nicotine and a chemical penetration enhancer (CPE) were used for evaluating drug penetration to understand how each enhancer impacts the permeability of nicotine as a model compound. The permeability measurements of human cadaver skin and Strat-M® membrane were performed with Franz diffusion cell methods accompanied by HPLC analysis. A good correlation of the permeability data was obtained through human cadaver skin and Strat-M® membrane. Thus, Strat-M® has the potential to be used as a screening tool for evaluating topical/transdermal formulations through the human cadaver skin.