Effect of vehicles on the transdermal delivery of melatonin across porcine skin in vitro

Melatonin is a good candidate for transdermal drug delivery considering its variable oral absorption, a short biological half-life and extensive first pass metabolism. The purpose of this study was to investigate the effect of various vehicles on the in vitro permeation of melatonin across porcine skin. The skin permeation studies were carried out with vertical diffusion cells using dermatomed porcine skin. The flux of melatonin from isopropyl myristate, Lauroglycol FCC and ethanol were respectively 1.5, 1.4 and 1.3 times higher than that observed with water (P<0.001). However, flux values of melatonin with Labrasol(TM), propylene glycol and mineral oil were significantly lower than that of water (P<0.001). There was no significant difference between the flux of melatonin from the following vehicles: Transcutol(TM), Phosol 50 PG, ethyl oleate, PEG 400 and water (F=0.2082, P>0.05). In general, vehicles with high melatonin solubility showed low permeability coefficient values. The flux had no correlation to the solubility data, suggesting that high solubility values do not translate to high drug permeation. The present study suggests that isopropyl myristate, Lauroglycol FCC and ethanol may be used as potential vehicles in the transdermal delivery of melatonin. (C) 2002 Elsevier Science B.V. All rights reserved.