Relationship between lipophilicity and skin permeability of various drugs from an ethanol/water/lauric acid system.
The in vitro skin permeability of 16 drugs with a wide range of lipophilicity (log P; -0.95-4.40) was evaluated by the use of an ethanol/water (60/40) binary vehicle with or without lauric acid as a permeation enhancer. The enhancing effect by the addition of lauric acid to the ethanol/water (60/40) binary vehicle could be observed from the aspect of both permeation rate and lag time. The permeation rate increased with an increase in the hydrophilicity of the drugs. It was considered that lauric acid exerts an effect on both the polar and nonpolar regions of lipids of the stratum corneum, and the cooperative interaction of ethanol and lauric acid increases the participation of the polar pathway of drugs. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/water (60/40) binary vehicle with lauric acid showed a parabolic shape, with its peak at a more hydrophilic range (log P; 0.19) compared with other past references (log P; 2-3). The ethanol/water (60/40) binary vehicle with lauric acid appears to be a good candidate as a vehicle for transdermal therapeutic systems for hydrophilic drugs.
Lee
C K
CK
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Uchida
T
T
Kitagawa
K
K
Yagi
A
A
Kim
N S
NS
Goto
S
S
D020003:1-Octanol; D000779:Anesthetics, Local / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000378:metabolism; D005260:Female; D007850:Lauric Acids / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D000442:Octanols / Q000737:chemistry; D012869:Skin Absorption / Q000502:physiology*; D013329:Structure-Activity Relationship; D014867:Water / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism / Q000493:pharmacokinetics*
D000779:Anesthetics, Local; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D007850:Lauric Acids; D000442:Octanols; D014970:Xanthines; D014867:Water; C030358:lauric acid; D000431:Ethanol; D020003:1-Octanol