Topical oleo-hydrogel preparation of ketoprofen with enhanced skin permeability.
In an attempt to improve the skin penetration of ketoprofen, various transdermal formulations were prepared, and their in vitro skin permeability and in vivo percutaneous absorption were evaluated. In vitro permeation studies were performed using a modified Franz cell diffusion system in which permeation parameters such as cumulative amount at 8 hr Q8hr, steady-state flux Jss, or lag time tL were determined. In the in vivo percutaneous absorption study using the hairless mouse, maximum concentration Cmax and area under the curve at 24 hr AUC24h were measured. The optimal transdermal formulation (oleo-hydrogel formulation) of ketoprofen showed a Q8hr value of 227.20 micrograms/cm2, a Jss value of 29.61 micrograms/cm2/hr, and a tL value of 0.46 hr. The Q8hr and Jss values were about 10-fold (p < .01) higher than those (Q8hr = 19.61 micrograms/cm2; Jss = 2.66 micrograms/cm2/hr) from the K-gel and about 3.5-fold (p < .01) than those (Q8hr = 60.00 micrograms/cm2; Jss = 7.99 micrograms/cm2/hr) of the K-plaster. In the in vivo percutaneous absorption, the Cmax (6.82 micrograms/ml) and AUC24h (55.74 micrograms.hr/ml) values of the optimal formulation were significantly (p < .01) higher than those of K-gel and K-plaster. The relative bioavailability of the oleo-hydrogel following transdermal administration in reference to oral administration was about 37%, and the Cmax value (4.73 micrograms/cm2) in the hypodermis following topical administration was much higher than those from the conventional products (Cmax of K-gel and K-plaster were 0.92 +/- 0.19 microgram/cm2 and 1.27 +/- 0.37 microgram/cm2, respectively). These data demonstrate that the oleo-hydrogel formulation of ketoprofen was more beneficial than conventional products (K-gel and K-plaster) in enhancing transdermal permeation and skin absorption of ketoprofen. Furthermore, there was a good correlation between in vitro permeation parameters and in vivo percutaneous absorption parameters.
Rhee
G J
GJ
College of Pharmacy, Chung-nam National University, Taejon, Korea.
Woo
J S
JS
Hwang
S J
SJ
Lee
Y W
YW
Lee
C H
CH
D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D020100:Hydrogels / Q000737:chemistry*; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000097:blood / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D009821:Oils / Q000737:chemistry*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
D020100:Hydrogels; D009821:Oils; D007660:Ketoprofen