Effect of various vehicles on ketoprofen permeation across excised hairless mouse skin.
The effects of glycerides, short-chain alcohols, and their binary vehicles as donor components on the permeation of ketoprofen (KP) across the excised hairless mouse skin were evaluated with the modified LOVEDAY-type diffusion cell. Among single vehicles, Panasate 800 as tricaprylin appeared to be the most favorable lipophilic vehicle, with no toxicity and with a short lag time (0.9 h), and methanol (MeOH) or ethanol (EtOH) as hydrophilic single vehicles showed the highest KP permeation flux (244.1 and 134.1 micrograms/cm2/h, respectively). Furthermore, KP permeation was enhanced remarkably by the combination of EtOH and Panasate 800 compared with each single vehicle as reflected in the decreased lag time and increased flux. The greatest enhancement was observed in the EtOH/Panasate 800 (40/60) binary vehicle (permeation ratio at 24 h, 40.0%; steady-state flux, 314.0 micrograms/cm2/h; lag time, 3.7 h). Further investigations involving stripping studies and KP accumulation within the skin were performed to explain the mechanism of enhancement caused by the above binary vehicle. It was suggested that the mutual enhancement effect of EtOH/Panasate 800 (40/60) binary vehicle is due to decreasing the barrier ability of the stratum corneum by EtOH and the viable skin by Panasate 800.
Goto
S
S
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Uchida
T
T
Lee
C K
CK
Yasutake
T
T
Zhang
J B
JB
D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D015194:Diffusion Chambers, Culture; D000431:Ethanol / Q000494:pharmacology; D005989:Glycerides / Q000494:pharmacology; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D014677:Pharmaceutical Vehicles; D012869:Skin Absorption
D000438:Alcohols; D005989:Glycerides; D014677:Pharmaceutical Vehicles; D000431:Ethanol; D007660:Ketoprofen