Effect of Fatty acids on the Permeation of Melatonin across Rat and Pig Skin In-vitro and on the Transepidermal Water Loss in Rats In-vivo

Abstract

Transdermal delivery of melatonin would be advantageous in the treatment of sleep disorders considering the short biological half-life of melatonin and its variable bioavailability via the oral route. This study looked at suitable penetration enhancers for the transdermal permeation of melatonin. The permeation of melatonin was enhanced by all saturated and unsaturated fatty acids across both rat and porcine skin. There was a parabolic relationship between the carbon chain length of saturated fatty acids and the enhancement of melatonin permeation across rat and porcine skin. For rat skin, the maximum flux was observed with undecanoic acid (45.33 microg cm(-2) h(-1)) which enhanced the flux of melatonin 8.6 times compared with the control, whereas lauric acid produced the maximum flux of melatonin (24.98 microg cm(-2) h(-1); 4-7 times) across porcine skin. An increase in the number of double bonds in cis-9-octadecanoic acid increased the flux of melatonin across rat skin. In contrast, with porcine skin, the flux of melatonin decreased as the number of double bonds increased, although the flux values were not statistically significant. Treatment of rats with undecanoic acid, oleic acid and linolenic acid for 3 h using Hill top chamber enhanced the transepidermal water loss significantly. The maximum transepidermal water loss was observed with undecanoic acid and linolenic acid among saturated and unsaturated fatty acids, respectively. Nonanoic acid and myristic acid did not cause a significant change in the transepidermal water loss. The enhancement effect of saturated fatty acids on the permeation of melatonin was dependent on the chain-length of the fatty acid in both rat and porcine skin. While an increase in the number of double bonds in the fatty acid increased the flux of melatonin in rat skin, no significant difference in the flux was observed with porcine skin. The permeation enhancement of melatonin by saturated and unsaturated fatty acids across rat skin was significantly higher than that of porcine skin. A positive correlation was observed between the permeation enhancement effect of the fatty acids across rat skin in-vitro and the transepidermal water loss in rats in-vivo, suggesting that there is a similarity in the mechanism by which fatty acids enhance the permeation of melatonin and in the enhancement of transepidermal water loss. We conclude that saturated fatty acids such as undecanoic acid or lauric acid which showed maximum permeation across rat and porcine skin, respectively, may be used as potential penetration enhancers in the development of a transdermal delivery system for melatonin.

Effect of Polyoxyethylene Alkyl Esters on Permeation Enhancement and Impedance of Skin

“…TEWL Table 1. Solubility increased after treatment with nonanoic acid (9 carbon), and it further increased with undecanoic acid (11 carbon), however it decreased for myristic acid (14 carbon), below the level of control (Kandimalla et al, 1999). The fatty acid results show that low molecular weight PEG ester of lauric or OA (PEGML4 and PEGMO4) exhibited higher permeation enhancing effect than fatty acid itself.…”

Enhanced transdermal delivery of loratadine from the EVA matrix

“…Fatty acids have been shown to promote the skin permeation of drugs with a wide range of polarities through interactions with intercellular lipid domains (23)(24)(25). The efficacy of fatty acids is intrinsically linked to their structure, with differences evident between the saturated and unsaturated forms and those of a different hydrocarbon chain length (16,26). Unsaturated fatty acids, particularly those with the cis conformation and C 18 chain lengths, have been reported to be more effective enhancers than their saturated counterparts, promoting the permeation of such penetrants as naloxone (27) and flurbiprofen (28).…”

Skin Permeation Enhancement of Diclofenac by Fatty Acids

“…The kinks formed in the lipid structure of the skin tend to increase with more number of double bonds in the unsaturated fatty acids, which could further enhance the permeation of the drug (Tanojo et al 1997;Aungst et al 1986;Kandimalla et al 1999;Suhonen et al 1999). However, the flux of diclofenac was unaffected by the number of double bonds in the fatty acid enhancers as was reported of indomethacin (Morimoto et al 1996).…”