title: 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: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Matzneller
authors.forename: Angela
authors.initials: A
authors.lastname: Burian
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Martin
authors.forename: Ottavia
authors.initials: O
authors.lastname: Annoni
authors.forename: Vittoria
authors.initials: V
authors.lastname: Lauro
authors.forename: Raffaella
authors.initials: R
authors.lastname: Tacchi
authors.forename: Martin
authors.initials: M
authors.lastname: Brunner
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004304:Dosage Forms; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004304:Dosage Forms; D005480:Flurbiprofen