Effects of vehicles and enhancers on transdermal delivery of melatonin.
For a more effective transdermal delivery of melatonin (MT), the effects of vehicles and enhancers on its skin permeation and lag time were evaluated. Skin permeation study was conducted in Franz diffusion cells using excised hairless mouse skins. MT was analyzed by HPLC. As vehicles, ethanol (EtOH), polyethylene glycol 400 (PEG), or propylene glycol (PG) was used alone or mixed with a phosphate buffer. Binary vehicles (EtOH/buffer, PEG/buffer, PG/buffer) showed different effects on the skin permeation of MT and its lag time. Compared with the buffer alone, the PEG/buffer shortened the lag time of MT but reduced its skin permeation. EtOH/buffer significantly increased the flux of MT but prolonged the lag time with the content of EtOH. PG/buffer did not affect the lag time but slightly increased the skin permeation of MT at the higher content of PG (> or =80%). These results indicate that the composition of vehicles exerts significant influence but it per se might have limitation in modulating the transdermal delivery of MT. Next, one tested whether fatty acids could more effectively enhance the skin permeation of MT and shorten its lag time. Given the influence of vehicles on both permeation and lag time, PG was used as a vehicle for fatty acids. The permeation-enhancing effects of saturated fatty acids increased in the following order: C10>C12>C14>C16>C18. The saturated fatty acid, however, did not significantly shorten the lag time regardless of the carbon chain length. Meanwhile, similar to saturated lauric acid (C12), unsaturated oleic acid (C18) dramatically enhanced the skin permeability coefficient of MT more than 950-fold over the effect of PG alone. Moreover, oleic acid showed the shortest lag time (2.1 h). The results suggest that oleic acid in a suitable vehicle could more effectively enhance the skin permeation of MT and shorten its lag time than did the vehicles of various compositions.
Oh
H J
HJ
National Research Laboratory for Bioactives Delivery System, College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Ku, 151-742, Seoul, South Korea.
Oh
Y K
YK
Kim
C K
CK
D000818:Animals; D000431:Ethanol / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D008550:Melatonin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability; D014677:Pharmaceutical Vehicles; D012867:Skin / Q000378:metabolism*; D012995:Solubility
D005227:Fatty Acids; D014677:Pharmaceutical Vehicles; D000431:Ethanol; D008550:Melatonin