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Drug Res (Stuttg) 2013; 63(07): 331-337
DOI: 10.1055/s-0033-1337979
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Effect of the Formulation on the Bioequivalence of Meloxicam: Tablet and Suspension

S. A. Helmy
1   Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
,
H. M. El Bedaiwy
2   Department of Industrial Pharmacy, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
› Author Affiliations
Further Information

Publication History

received 15 January 2013

accepted 20 February 2013

Publication Date:
25 April 2013 (online)

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Abstract

Meloxicam is a non-steroidal anti-inflammatory drug of the enolic acid class that preferentially inhibits cyclooxygenase-2 imparting analgesic, antipyretic and anti-inflammatory effects. This study was conducted to evaluate the effect of formulation on the pharmacokinetics (PK) and comparative bioavailability of suspension (reference) and tablet (test) formulations of meloxicam. In this in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2 way, cross-over study with a washout period of 2 weeks. Under fasting conditions, 24 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of 15 mg meloxicam either as 10 mL of a marketed suspension or one tablet. Plasma samples were obtained over a 96-h interval and analyzed for meloxicam by reversed phase liquid chromatography with ultraviolet detection. A non-compartmental model was used to determine the PK parameters of meloxicam. The 90% confidence intervals for the ratio of log transformed values of Cmax, AUC0-t, and AUCt-∞ of the 2 treatments were within the acceptable range (0.8–1.25) for bioequivalence. From PK perspectives, in this small study in healthy Egyptian adult male volunteers, a single 15 mg dose of the tablet formulation was bioequivalent to a single 15 mg dose of the suspension formulation with no significant effect of formulation based on the US FDA’s regulatory definition. No adverse events occurred or were reported during the study and both formulations were well tolerated.

Key words

meloxicam - pharmacokinetics - bioavailability - ultraviolet - HPLC
 

  • References

  • 1 Sweetman SC. (ed.) Martindale: The complete drug reference. 34th Edn. Pharmaceutical Press; London: 56
  • 2 Engelhardt G, Homma D, Schlegel K et al. Anti-inflammatory analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance. Inflamm Res 1995; 44: 423-433
    CrossrefPubMedSearch in Google Scholar
  • 3 Stei P, Püschner H. Intramuscular tolerance of meloxicam compared to piroxicam and diclofenac in rabbits. Scand J Rheumatol 1994; 98 (Suppl) Abstract No.109
    PubMedSearch in Google Scholar
  • 4 Mobic® Tablets 7.5 mg and 15 mg – Food and Drug Administration. http://www.fda.gov/ohrms/dockets/ac/06/briefing/20064254b_14_05_KP%20MeloxicamFDAlabel82005.pdf [Last accessed January 15, 2013]
    PubMed
  • 5 Türck D, Busch U, Heinzel G et al. Clinical pharmacokinetics of meloxicam. Arzneimittelforschung 1997; 47: 253-258
    PubMedSearch in Google Scholar
  • 6 Davies NM, Skjodt NM. Clinical pharmacokinetics of meloxicam a cyclo-oxygenase-2 preferential non-steroidal anti-inflammatory drug. Clin Pharmacokinet 1999; 36: 115-126
    CrossrefPubMedSearch in Google Scholar
  • 7 Chesne C, Guyomard C, Guillouzo A et al. Metabolism of meloxicam in human liver involves cytochromes P450 2C9 and 3A4. Xenobiotica 1998; 28: 1-13
    CrossrefPubMedSearch in Google Scholar
  • 8 Schmid J, Busch U, Heinzel G et al. Meloxicam pharmacokinetics and metabolic pattern after intravenous infusion and oral administration to healthy subjects. Drug Metab Dispos 1995; 23: 1206-1213
    PubMedSearch in Google Scholar
  • 9 Hasan SM, Shoaib MH, Hassan F et al. Bioequivalence studies of two brands of meloxicam tablets in healthy Pakistani volunteers. Pak J Pharm Sci 2009; 22: 199-204
    PubMedSearch in Google Scholar
  • 10 Schulz HU, Steinijans VW. Striving for standards in bioequivalence assessment: a review. Int J Clin Pharmacol Ther Toxicol 1992; 30: S1-S6
    PubMedSearch in Google Scholar
  • 11 Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm 1987; 15: 657-680
    CrossrefPubMedSearch in Google Scholar
  • 12 Barrett JS, Batra V, Chow A et al. PhRMA perspective on population and individual bioequivalence. J Clin Pharmacol 2000; 40: 561-571
    CrossrefPubMedSearch in Google Scholar
  • 13 U.S. Food and Drug Administration Centre for Drug Evaluation and Research (FDA). Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products – General Considerations. Office of Training and Communications, Division of Communications Management, Drug Information Branch, HFD-210, Rockville MD 20857, March 2003 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070124.pdf [Last accessed January 3rd, 2013]
    PubMed
  • 14 EMEA/CPMP/EWP/1401/98 . Note for guidance on the investigation of bioavailability and bioequivalence. EMEA; London: 26 July 2001. EMEA/CPMP/EWP/QWP/1401/98 Rev.1/Corr*. Guideline on the investigation of bioequivalence. London, 20 January 2010. Available at http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC50007003 pdf [Last accessed January 3rd, 2013]
    Search in Google Scholar
  • 15 Executive Board of Health Ministries for Gulf States, Approved Guidelines on Drug Bioavailability and Bioequivalence Requirements in the Executive Board of Health Ministries for Gulf States, May 2005.P.O. Box 84983 Riyadh 11681, Kingdom of Saudi Arabia
    PubMed
  • 16 Velpandian T, Jaiswal J, Bhardwaj RK et al. Development and validation of a new high-performance liquid chromatographic estimation method of meloxicam in biological samples. J Chromatogr B Biomed Sci Appl 2000; 738: 431-436
    CrossrefPubMedSearch in Google Scholar
  • 17 Bae JW, Kim MJ, Jang CG et al. Determination of meloxicam in human plasma using a HPLC method with UV detection and its application to a pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 859: 69-73
    PubMedSearch in Google Scholar
  • 18 Shirako J, Kawasaki M, Komine K et al. Simultaneous determination for oxicam non-steroidal anti-inflammatory drugs in human serum by liquid chromatography-tandem mass spectrometry. Forensic Sci Int 2012; S0379-0738(12)00534-8
    PubMedSearch in Google Scholar
  • 19 Ji HY, Lee HW, Kim YH et al. Simultaneous determination of piroxicam, meloxicam and tenoxicam in human plasma by liquid chromatography with tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2005; 826: 214-219
    PubMedSearch in Google Scholar
  • 20 Lee HW, Ji HY, Kim HY et al. Liquid chromatography-tandem mass spectrometry method for the determination of meloxicam and its metabolite 5-carboxymeloxicam in human plasma. Bioanalysis 2009; 1: 63-70
    CrossrefPubMedSearch in Google Scholar
  • 21 Yuan Y, Chen X, Zhong D. Determination of meloxicam in human plasma by liquid chromatography-tandem mass spectrometry following transdermal administration. J Chromatogr B 2007; 852: 650-654
    CrossrefPubMedSearch in Google Scholar
  • 22 Dasandi B, Shivaprakash, Saroj H. et al. LC determination and pharmacokinetics of meloxicam. J Pharm Biomed Anal 2002; 28: 999-1004
    CrossrefPubMedSearch in Google Scholar
  • 23 Marcelín-Jiménez G, Hernández JA, Angeles AP et al. Bioequivalence evaluation of two brands of meloxicam tablets (Promotion and Mobicox): Pharmacokinetics in a healthy female Mexican population. Biopharm Drug Dispos 2005; 26: 167-171
    CrossrefPubMedSearch in Google Scholar
  • 24 Rigato HM, Mendes GD, Borges NC et al. Meloxicam determination in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) in Brazilian bioequivalence studies. Int J Clin Pharmacol Ther 2006; 44: 489-498
    PubMedSearch in Google Scholar
  • 25 Gschwend MH, Erenmemişoğlu A, Martin W et al. Pharmacokinetic and bioequivalence study of meloxicam tablets in healthy male subjects. Arzneimittelforschung 2007; 57: 264-268
    Thieme ConnectPubMedSearch in Google Scholar
  • 26 Ahmad M, Murtaza G, Akhtar N et al. Bioequivalence study of two brands of meloxicam tablets in healthy human Pakistani male subjects. Acta Pol Pharm 2011; 68: 115-119
    PubMedSearch in Google Scholar
  • 27 U.S. Food and Drug Administration Centre for Drug Evaluation and Research (FDA) . Guidance for Industry-Bioanalytical Method Validation. Silver Spring, MD: Center for Drug Evaluation and Research, US Department for Health and Human Services; 2001. Available at: http://www.fda.gov/downloads/Drugs/…/Guidances/ucm070107.pdf [Last accessed January 3rd, 2013]
  • 28 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice. August 2010 www.ich.org/fileadmin/Public_Web_Site/ICH…/E2F_Step_4.pdf [Last Accessed January 5, 2013]
    PubMed
  • 29 Gibaldi M, Perrier D. In: Pharmacokinetics. Swarbrick J. (eds.). Informa Healthcare USA, Inc; New York, U.S.A.: 1982
    Search in Google Scholar
  • 30 Hedaya MA In: Basic pharmacokinetics. Taylor and Francis. (eds.). Taylor and Francis group, 6000 Broken Sound Parkway NW, Suit 300; Boca Raton, FL 33487-2742, England: 2007
    Search in Google Scholar
  • 31 Diletti E, Hauschke D, Steinijans VW. Sample size determination for bioequivalence assessment by means of confidence intervals. Int J Clin Pharmacol Ther Toxicol 1992; 30 (Suppl. 01) S51-S58
    PubMedSearch in Google Scholar
  • 32 SAS Institute Inc . SAS/STAT User’s guide, Version 6. 4th Edition Vol. 2. SAS Institute; Cary, NC: 1990
    Search in Google Scholar
  • 33 Westlake WF. Use of confidence interval in analysis of comparative bioavailability trials. J Pharm Sci 1972; 61: 1340-1341
    CrossrefPubMedSearch in Google Scholar
  • 34 Mandallaz D, Mau J. Comparison of different methods of decision making in bioequivalence assessments. Biometrics 1981; 37: 213-222
    CrossrefPubMedSearch in Google Scholar
  • 35 Locke S. An exact confidence interval from untransformed data for the ratio of two formulations means. J Pharmacokinet Biopharm 1984; 12: 649-655
    CrossrefPubMedSearch in Google Scholar