Abstract

*A new formulation of the nonselective NSAID diclofenac sodium suitable for intravenous bolus injection has been developed using hydroxypropyl beta-cyclodextrin as a solubility enhancer (HPbetaCD diclofenac). * HPbetaCD diclofenac intravenous bolus injection was shown to be bioequivalent to the existing parenteral formulation of diclofenac containing propylene glycol and benzyl alcohol as solubilizers (PG-BA diclofenac), which is relatively insoluble and requires slow intravenous infusion over 30 minutes. * Single-dose HPbetaCD diclofenac 3.75, 9.4, 18.75, 25, 37.5, 50 and 75 mg administered by intravenous bolus injection produced significantly greater responses than placebo for total pain relief (TOTPAR) over 6 hours or pain intensity at 4 hours in the treatment of moderate or severe postoperative dental pain in randomized, double-blind trials. HPbetaCD diclofenac 37.5 and 75 mg were similar in efficacy to intravenous bolus ketorolac 30 mg. * In a well controlled trial, single-dose HPbetaCD diclofenac 75 mg intravenous bolus injection was shown to be superior to PG-BA diclofenac 75 mg intravenous infusion with respect to TOTPAR over 4 hours, indicating faster onset of analgesia in the treatment of moderate or severe postoperative dental pain. Both HPbetaCD diclofenac and PG-BA diclofenac were superior to placebo. * HPbetaCD diclofenac was generally well tolerated during single-dose treatment of postoperative pain. The tolerability profile was similar to that of PG-BA diclofenac, but with a lower incidence of thrombophlebitis.