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Combined effect of cyclic monoterpenes and ethanol on percutaneous absorption of diclofenac sodium.

The combined effect of cyclic monoterpenes and ethanol on the percutaneous absorption of diclofenac sodium (DFS) from gel ointments was investigated in vivo in rats. The enhancing activity of terpenes was significantly affected by the concentration of ethanol formulated in the gel ointments. At a lower concentration of ethanol (20%), 1,8-cineole was observed to be the most effective. On the other hand, d-limonene showed strong activity when the large amount of ethanol was formulated (40%). A synergistic effect between terpenes and ethanol on the percutaneous absorption of DFS was significantly observed in cases of 1,8-cineole and l-menthol using an analysis of variance (ANOVA). When the diclofenac (DF) free form was formulated in gel ointment, the percutaneous absorption was significantly reduced. The reduction of the percutaneous absorption was closely related to the decrease in pH of the gel ointment owing to the free form of DF which was formulated.