Skin permeation enhancement effect and skin irritation of saturated fatty alcohols

Though the skin permeation enhancement effect of chemical penetration enhancers has been studied extensively, their skin irritation potential has not been adequately investigated. The objective of this study was to evaluate the skin permeation enhancement effect and skin irritation of saturated fatty alcohols using melatonin as a model compound. A saturated solution of melatonin in a mixture of water and ethanol (40:60) containing 5% w/v of saturated fatty alcohol was used in the skin permeation studies using Franz diffusion cells. For skin irritation studies, 230 mul of fatty alcohol solution was applied on the dorsal surface of the hairless rats using Hill top chamber. The skin irritation was evaluated by visual scoring method and bioengineering methods such as measurement of transepidermal water loss (TEWL) and skin blood flow. The flux of melatonin across hairless rat skin was found to be dependent on the carbon chain length of the fatty alcohols, with decanol showing the maximum permeation of melatonin. All fatty alcohols increased the TEWL and skin blood flow significantly compared with the vehicle. The fatty alcohols (decanol, undecanol and lauryl alcohol), which showed greater permeation of melatonin, also produced greater TEWL, skin blood flow and erythema. Tridecanol and myristyl alcohol showed lower permeation enhancement effect but caused greater skin irritation. Octanol and nonanol may be the most useful enhancers for the transdermal delivery of melatonin considering their lower skin irritation and a reasonably good permeation enhancement effect. However, further studies are needed to ascertain their safety as skin penetration enhancers. Skin permeation and skin irritation in experimental animals such as rats are generally higher compared with human skin. Further studies in human volunteers using fatty alcohols at the concentrations of 5% or lower may provide useful information on the utility of these fatty alcohols as permeation enhancers. (C) 2002 Elsevier Science B.V. All rights reserved.