Transdermal behaviour of the N-alkylamide spilanthol

N-alkylamides are a group of bioactive molecules found in several plants from the geni Echinacea, Xanthoxylum and Spilanthes. Extracts and formulations derived from these plants are not only orally used but are applied on the skin as well. However, there is no specific information available about the intrinsic local pharmacokinetics of N-alkylamides after topical application on human skin, questioning the role of this mode of administration. Therefore, we have investigated the transdermal behavior of spilanthol as N-alkylamide model compound. Two pharmaceutically accepted vehicles (ethanol and propylene glycol based aqueous solutions), combined with three different receptor fluids (PBS, PBS/HPBCD, EtOH/H2O), were applied on split-thickness human skin in a Franz diffusion system. However, seen the confounding penetration modifying effects of those solvents, the permeation characteristics of spilanthol in a solvent-independent (100% aqueous dose solution) way was also obtained using an extrapolation approach with different organic solvent/H2O ratios. It was shown that spilanthol did permeate the skin. Partitioning (Km) was strongly dependent on the donor-vehicle composition, while diffusion (Dm) was mainly influenced by the receptor fluid composition. The following extrapolated quantitative primary parameters were obtained (mean ± SEM): Kp,aq = 3.31 ∙ 10-3 ± 0.28 ∙ 10-3 cm/h, Dm, aq = 1.90 ∙ 10-4 ± 0.07 ∙ 10-4 cm²/h and Km, aq = 7.27 ∙ 10-1 ± 1.56 ∙ 10-1 [1]. References [1] J. Boonen, B. Baert, N. Roche, C. Burvenich and B. De Spiegeleer. Transdermal behaviour of the N-alkylamide spilanthol (affinin) from Spilanthes acmella (Compositae) extracts, 2009, publication submitted