Skin permeability of various drugs with different lipophilicity.
The in vitro and in vivo skin permeability of 16 drugs with a wide span of lipophilicity (log P ranging from -0.95 to 4.40) was evaluated with an ethanol/panasate 800 (tricaprylin) (40/60) system as a lipophilic vehicle. The ethanol/panasate 800 (40/60) binary vehicle remarkably improved the in vitro skin permeability of the drugs across excised hairless mouse skin compared with ethanol or panasate 800 as single vehicles. The in vivo skin permeability of the large majority of the drugs across abdominal rat skin also showed high permeation rates and short lag times. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/panasate 800 (40/60) binary vehicle indicated parabolic shapes with their peaks at much greater hydrophilic range (log P: -0.88 for in vitro, -0.83 for in vivo) compared with other past references (log P: 2-3). The results suggest that the lipophilicity of a drug is a main factor for prediction of the skin permeability of the drug and that the ethanol/panasate 800 (40/60) lipophilic binary vehicle would be a good candidate as a vehicle for future clinical application of 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
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol; D005069:Evaluation Studies as Topic; D005260:Female; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008812:Mice, Hairless; D000442:Octanols; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D014677:Pharmaceutical Vehicles; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000502:physiology*; D013056:Spectrophotometry, Ultraviolet; D014867:Water
D008055:Lipids; D000442:Octanols; D004364:Pharmaceutical Preparations; D014677:Pharmaceutical Vehicles; D014867:Water; D000431:Ethanol