Development of novel percutaneous absorption promoters

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The promoting effect of menthol ethylether derivative (MET) on the percutaneous absorption of ketoprofen from alcoholic hydrogels was evaluated in rats. The skin permeation of ketoprofen was analyzed by a membrane diffusion model, and the diffusion and partition parameters of ketoprofen were estimated. The diffusion parameter was remarkably enhanced when the hydrogel containing 0.5% MET was applied, while further increase of MET (1-3%)resulted in a little enhancement of skin permeation of ketoprofen. On the other hand, the partition parameter was hardly changed with an increase of MET concentration in the hydrogels.To evaluate in vivo percutaneous absorption of ketoprofen from hydrogels containing MET (0-3%), a pharmacokinetic model was derived on the assumption of a constant penetration rate (Rp). Similar to the results obtained with the in vitro experiment, Rp values increased significantly by the administration of hydrogels containing a littel amount of MET (-0.5%). Such promoting action was also observed with menthol, however, the degreeof enhancement with menthol was poor, compared with MET.At least 2% of menthol was required so as obtain an equal activity observed with 0.5% MET.The anti-inflammatory action of ketoprofen hydrogels containing MET was investigated with a rat paw edema test. When a little amount of MET (0.5%) was formulated in the hydrogel, a significant inhibition to the edema was observed. More than 2% of menthol was required so as to obtain the equal activity recognized in the hydrogel with 0.5% MET, indicating that the pharmacological activity of ketoprofen absorbed percutaneously correlated well with pharmacokinetic results.