Topical oleo-hydrogel preparation of ketoprofen with enhanced skin permeability

In an attempt to improve the skin penetration of ketoprofen, various transd ermal 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 perme ation parameters such as cumulative amount at 8 hr Q(8hr), steady-state flu x J(ss), or lag time t(L) were determined. In the in vivo percutaneous abso rption study using the hairless mouse, maximum concentration C-max and area under the curve at 24 hr AUC(24h) were measured. The optimal transdermal f ormulation (oleo-hydrogel formulation) of ketoprofen showed a Q(8hr) value of 227.20 mu g/cm(2), a J(ss) value of 29.61 mu g/cm(2)/hr, and a t(L) valu e of 0.46 hr. The Q(8hr) and J(ss) values were about 10-fold (p < .01) high er than those (Q(8hr) = 19.61 mu g/cm(2); J(ss) = 2.66 mu g/cm(2)/hr) from the K-gel and about 3.5-fold (p < .01) than those (Q(8hr) = 60.00 mu g/cm(2 ); J(ss) = 7.99 mu g/cm(2)/hr) of the K-plaster. In the in vivo percutaneou s absorption, the C-max (6.82 mu g/ml) and AUC(24h) (55.74 mu g . hr/ml) va lues of the optimal formulation were significantly (p < .01) higher than th ose of K-gel and K-plaster. The relative bioavailability of the oleo-hydrog el following transdermal administration in reference to oral administration was about 37%, and the C-max value (4.73 mu g/cm(2)) in the hypodermis fol lowing topical administration was much higher than those from the conventio nal products (C-max of K-gel and K-plaster were 0.92 +/- 0.19 mu g/cm(2) an d 1.27 +/- 0.37 mu g/cm(2), respectively). These data demonstrate that the oleo-hydrogel formulation of ketoprofen was more beneficial than convention al products (K-gel and K-plaster) in enhancing transdermal permeation and s kin absorption of ketoprofen. Furthermore, there was a good correlation bet ween in vitro permeation parameters and in vivo percutaneous absorption par ameters.