Effect of Vehicles on Diclofenac Permeation across Excised Rat Skin

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The in vitro percutaneous permeation of diclofenac from various vehicles was examined using rat abdominal skin as a model membrane. The oleaginous vehicles used in this study consisted of three components : i.e. fatty acid, fatty acid ester and nonpolar oil. The solubilities of sodium diclofenac in formulated vehicles were above 0.2 M. The effect of each oleaginous component in the vehicle on the permeation of diclofenac across the skin was in the following order : oleic aicd>isostearic acid, diisopropyl adipate=diethyl sebacate>Panasate 875 and squalane>liquid paraffin. To clarify the reason for the differences in permeation among the fatty acid esters, the release of diclofenac through either porous or lipoidal membranes from these vehicles in vitro and the solubility of sodium diclofenac in the vehicles were studied. However, no relationship was observed between the release rate or solubility and skin permeability. The skin permeation of diclofenac increased 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 significantly enhanced the permeation of diclofenac from these preparations. These results suggest that the emulsion and cream prepared in this study are useful for development for practical purposes.
社団法人日本薬学会の論文
1995-04-15

Effect of Vehicles on Diclofenac Permeation across Excised Rat Skin

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