EFFECT OF VEHICLES ON DICLOFENAC PERMEATION ACROSS EXCISED RAT SKIN

The in vitro percutaneous permeation of diclofenac from various vehicl es was examined using rat abdominal skin as a model membrane. The olea ginous vehicles used in this study consisted of three components: i.e. fatty acid, fatty acid ester and nonpolar oil. The solubilities of so dium diclofenac in formulated vehicles were above 0.2 M. The effect of each oleaginous component in the vehicle on the permeation of diclofe nac across the skin was in the following order: oleic aicd > isosteari c acid, diisopropyl adipate = diethyl sebacate > Panasate 875 and squa lane > liquid paraffin. To clarify the reason for the differences in p ermeation among the fatty acid esters, the release of diclofenac throu gh either porous or lipoidal membranes from these vehicles in vitro an d the solubility of sodium diclofenac in the vehicles were studied. Ho wever, no relationship was observed between the release rate or solubi lity and skin permeability. The skin permeation of diclofenac increase d following pretreatment with diisopropyl adipate or diethyl sebacate, but not with middle chain triglyceride (Panasate 875). These results suggested that the main reason may be the enhancement effect of fatty acid esters. Emulsions and creams containing 3% sodium diclofenac were prepared using the above oleaginous vehicles. A large flux and short lag time were observed in these preparations compared with an aqueous suspension of sodium diclofenac. The incorporation of urea significant ly enhanced the permeation of diclofenac from these preparations. Thes e results suggest that the emulsion and cream prepared in this study a re useful for development for practical purposes.