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 Q(8hr), steady-state flux J(ss), or lag time t(L) were determined. In the in vivo percutaneous absorption study using the hairless mouse, maximum concentration C(max) and area under the curve at 24 hr AUC(24h) were measured. The optimal transdermal formulation (oleo-hydrogel formulation) of ketoprofen showed a Q(8hr) value of 227.20 μg/cm², a J(ss) value of 29.61 μg/cm²/hr, and a t(L) value of 0.46 hr. The Q(8hr) and J(ss) values were about 10-fold (p < .01) higher than those (Q(8hr) = 19.61 μg/cm²; J(ss) = 2.66 μg/cm²/hr) from the K-gel and about 3.5-fold (p < .01) than those (Q(8hr) = 60.00 μg/cm²; J(ss) = 7.99 μg/cm²/hr) of the K-plaster. In the in vivo percutaneous absorption, the C(max) (6.82 μg/ml) and AUC(24h) (55.74 μg · 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 C(max) value (4.73 μg/cm²) in the hypodermis following topical administration was much higher than those from the conventional products (C(max) of K-gel and K-plaster were 0.92 ± 0.19 μg/cm² and 1.27 ± 0.37 μg/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.