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 (Cmax), time to maximum plasma concentration (Tmax), area under the plasma concentration-time curve from time zero to 24 hours (AUC0–t), area under the plasma concentration-time curve from time zero to infinity (AUC0–∞) 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 Cmax 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 Cmax and AUCs. Moreover, mean Tmax 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.

Brogden RN, et al: Flurbiprofen: a review of its pharmacological properties and therapeutic use in rheumatic diseases. Drugs 1979;18:417–438.
Flurbiprofen; in Dollery C: Therapeutic Drugs, 2nd edition. Edinburgh, Churchill Livingstone, 1999.
Blagden M, et al: Multidose flurbiprofen 8.75 mg lozenges in the treatment of sore throat: a randomised, double-blind, placebo-controlled study in UK general practice centres. Int J Clin Pract 2002;56:95–100.
Schachtel BP, et al: Demonstration of dose response of flurbiprofen lozenges with the sore throat pain model. Clin Pharmacol Ther 2002;71:375–380.
Battisti N: The evaluation of the analgesic and anti-inflammatory effects of flurbiprofen mouthwash and 100-mg tablets in oral medicine. Minerva Stomatol 1994;43:141–144.
Christian JLP, Shaw H, Charlesworth A, Richens A: Local and general tolerability of flurbiprofen lozenges in healthy volunteers. Pharmacol Res 1999;39:104.
Brooks CD, et al: Clinical safety of flurbiprofen. J Clin Pharmacol 1990;30:342–351.
Abramson SB: Clinical guidelines: expert recommendations for NSAID use: a user-friendly model? Nat Rev Rheumatol 2011;7:133–134.
Stalker DJ, Pollock SR: Bioavailability of flurbiprofen following buccal administration. Pharm Res 1991;8:605–607.
Davies NM: Clinical pharmacokinetics of flurbiprofen and its enantiomers. Clin Pharmacokinet 1995;28:100–114.
Benactiv Gola® summary of product characteristics. Slough, Reckitt Benckiser Healthcare, 2009.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.