A Randomised, Two-Period, Cross-Over, Open-Label Study to Evaluate the Pharmacokinetic Profiles of Single Doses of Two Different Flurbiprofen 8.75-mg Lozenges in Healthy Volunteers

Abstract

Aims: To compare the bioavailability of a new oromucosal formulation of flurbiprofen 8.75-mg lozenges, developed by Alfa Wassermann S.p.A. (test drug) to that of marketed flurbiprofen 8.75-mg lozenges (Benactiv Gola®, reference drug). Methods: This was an open, randomised, two-period, crossover, pharmacokinetic (PK) study in which flurbiprofen plasma levels were compared in 12 healthy volunteers after the administration of single doses (8.75 mg × 2) of two different oromucosal lozenges to be sucked and slowly dissolved in the mouth. A wash-out period of at least 7 days separated the two study periods. Blood samples were collected prior to dosing and at predefined intervals for 24 h after dose. Flurbiprofen plasma concentrations were determined by liquid chromatography/tandem mass spectrometry. PK parameters maximum plasma concentration (C_max), time to maximum plasma concentration (T_max), area under the plasma concentration-time curve from time zero to 24 hours (AUC_0–t), area under the plasma concentration-time curve from time zero to infinity (AUC_0–∞) and half-life were calculated and compared by analysis of variance using treatment, period and sequence as sources of variation. Bioequivalence between the two formulations was based on 90% confidence intervals of the ratio of the geometric means of C_max and AUC falling within the 0.80–1.25 range as defined in bioequivalence guidelines by regulators. Tolerability of the two formulations was assessed by adverse event monitoring, routine laboratory tests, physical examination, electrocardiographic tracing and vital sign measurements. Results: All enrolled subjects completed the study. Bioequivalence without significant treatment effect was demonstrated between the test drug/reference drug ratios of mean C_max and AUCs. Moreover, mean T_max was superimposable. No safety parameter presented a clinically relevant variation after administration of either formulation that were therefore well tolerated. Conclusion: The new formulation of flurbiprofen 8.75-mg compressed lozenges developed by Alfa Wassermann S.p.A. is bioequivalent to the reference product flurbiprofen 8.75-mg lozenges (Benactiv Gola) in healthy volunteers.