Skin permeation enhancement of tegafur by ethanol/panasate 800 or ethanol/water binary vehicle and combined effect of fatty acids and fatty alcohols.
The effects of vehicle and enhancer on the skin permeation of tegafur across excised hairless mouse skin were investigated. Ethanol, water, panasate 800 (tricaprylin), and their mixtures were used as vehicles, and then a series of fatty acids or fatty alcohols was employed as representative enhancers. The skin permeability of tegafur was dramatically increased by the combination of ethanol and panasate 800, whereas the combination of ethanol and water resulted in only a little increase. The greatest permeation ratio (56.8% of dose at 12 h) was obtained with the ethanol/panasate 800 (40/60) binary vehicle. Furthermore, the skin permeability of tegafur could be enhanced by the addition of fatty acids or fatty alcohols to ethanol/panasate 800 (40/60) and ethanol/water (60/40) binary vehicles. The infinite dose studies suggested that panasate 800 decreased the lag time by increasing the diffusion of tegafur, and ethanol increased the permeation rate by increasing the partition of tegafur into skin. The effects of fatty acids or fatty alcohols added to ethanol as a single vehicle were dramatic, but did not appear in the case of panasate 800 as a single vehicle. In conclusion, panasate 800 was an excellent hydrophobic vehicle in that it minimized time lag and promoted tegafur permeability combined with ethanol. This improvement was further promoted when enhancers were added.
Lee
C K
CK
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Uchida
T
T
Noguchi
E
E
Kim
N S
NS
Goto
S
S
D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability; D014677:Pharmaceutical Vehicles; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D005641:Tegafur / Q000493:pharmacokinetics*; D014280:Triglycerides / Q000494:pharmacology*
D002210:Caprylates; D005227:Fatty Acids; D005233:Fatty Alcohols; D014677:Pharmaceutical Vehicles; D014280:Triglycerides; D005641:Tegafur; D000431:Ethanol; C003637:tricaprylin