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The aim of this work was to investigate the effect of the stability of hydrogen-bonded ion pairs with organic amines on transdermal penetration of teriflunomide (TEF). Five organic amines, diethylamine (DEtA), triethylamine (TEtA), diethanolamine (DEA), triethanolamine (TEA), and N-(2′-hydroxyethanol)-piperdine (NP), were chosen to form ion pairs with TEF separately, and the passage of each TEF ion pair through the rabbit skin was evaluated in vitro. FTIR and 1H NMR spectroscopy were performed to confirm the formation of ion pairs between TEF and organic amines in solution. The stability parameter of ion pairs in terms of ion-pair lifetimes (Tlife) was calculated from the NMR data. TEF could form ion pairs with these amines via hydrogen bond. The formation of ion pairs enhanced the percutaneous absorption of TEF except TEF–DEA. It was found that, for most studied organic amines, the longer the ion-pair lifetime, the higher the flux of skin permeation. The stability of TEF ion pairs was a pivotal factor influencing the skin permeation of TEF.