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.

[1]  T. Uchida,et al.  Skin permeation enhancement of tegafur by ethanol/panasate 800 or ethanol/water binary vehicle and combined effect of fatty acids and fatty alcohols. , 1993, Journal of pharmaceutical sciences.

[2]  J. Ostrenga,et al.  Significance of vehicle composition. I. Relationship between topical vehicle composition, skin penetrability, and clinical efficacy. , 1971, Journal of pharmaceutical sciences.

[3]  C. Hansch,et al.  Lipophilic character and biological activity of drugs. II. The parabolic case. , 1973, Journal of pharmaceutical sciences.

[4]  C. Hansch,et al.  The effect of intramolecular bydrophobic bonding on partition coefficients , 1967 .

[5]  J. Bridges,et al.  A re-evaluation of the importance of partition coefficients in the gastrointestinal absorption of anutrients. , 1974, The Journal of pharmacology and experimental therapeutics.

[6]  F. Bonina,et al.  1-Alkylazacycloalkan-2-one esters as prodrugs of indomethacin for improved delivery through human skin , 1991 .

[7]  A. Leo,et al.  Partition coefficients and their uses , 1971 .

[8]  T Yano,et al.  Skin permeability of various non-steroidal anti-inflammatory drugs in man. , 1986, Life sciences.

[9]  S. Yamashita,et al.  5-Fluorouracil derivatives with serum protein binding potencies. , 1989, Chemical and pharmaceutical bulletin.

[10]  T. Uchida,et al.  Effect of various vehicles on ketoprofen permeation across excised hairless mouse skin. , 1993, Journal of pharmaceutical sciences.

[11]  H. Colom,et al.  A comparative in vitro study of transdermal absorption of a series of calcium channel antagonists. , 1991, Journal of pharmaceutical sciences.

[12]  J. H. Rytting,et al.  In vitro transport of sodium diclofenac across rat abdominal skin: effect of selection of oleaginous component and the addition of alcohols to the vehicle. , 1991, Chemical & pharmaceutical bulletin.