COMPARATIVE BIOAVAILABILITY OF A DISPERSIBLE FORMULATION OF DICLOFENAC AND FINDING OF DOUBLE PLASMA PEAKS

We carried out a comparative study of the bioavailability of a typical , enteric-coated diclofenac with regard to a new dispersible formulati on whose faster dissolution results in an earlier onset of its analges ic effect. This randomized, crossover study was conducted in 12 health y male volunteers, who received in fasting 100 mg of enteric-coated di clofenac (Dolotren, FAES) and 100 mg of dispersible diclofenac (Dolotr en Dispersable, FAES), with one-week interval between both. Blood samp les were taken at pre-established times during the 24 hours after dosi ng, and plasma concentrations of diclofenac were determined by HPLC. P ossible adverse experiences were monitored with a check-list, and bloo d and urinalysis were performed for safety assessment. The dispersible formulation showed a relative extent of bioavailability between 78% a nd 99% (90% CI) for the AUC(0-infinity) being the 90% CI for the C-max 63% - 129%. The time to C-max (T-max) was significantly shorter with the dispersible than with the enteric-coated formulation (95% CI for t he difference = 1.5 - 4.25 hours) as the T-1ag or time to measurable p lasma concentrations (1.9 - 4.2 hours, 95% CI). A relevant feature in the study was the finding of a second peak at 2 - 2.5 hours post-dosin g in 7 out of 11 profiles of subjects receiving the dispersible formul ation. Both formulations were well tolerated in clinical and laborator y terms. In conclusion, the new dispersible formulation of diclofenac allows absorption to begin more rapidly and plasma peak is reached ear lier, a fact that may be relevant to the analgesic treatment of acute pain.