COMPARATIVE DISSOLUTION STUDIES OF WARFARIN SODIUM TABLETS: INFLUENCE OF AGITATION RATE, DISSOLUTION MEDIUM, AND USP APPARATUS
Keywords:Flow-through cell method, Reference tablets, USP basket and paddle apparatuses, Warfarin sodium
Objective: The aim of this study was to carry out comparative dissolution studies with warfarin sodium reference tablets under the hydrodynamic environments generated by the USP basket and paddle apparatus and flow-through cell using different agitation rates and dissolution media.
Methods: Dissolution profiles were obtained with the USP basket and paddle apparatus at 50, 75, and 100 rpm and 900 ml of water as dissolution medium. After this, dissolution profiles of warfarin sodium were obtained with the USP paddle apparatus and flow-through cell method using 0.1 N hydrochloric acid, acetate buffer pH 4.5, phosphate buffer pH 6.8, and water. Spectrophotometric determination at 308 nm was carried out during 30 min. Dissolution profiles were compared with model-independent and model-dependent approaches.
Results: Significant differences were found with mean dissolution time and dissolution efficiency at 50 and 75 rpm (*P<0.05). Makoid-Banakar was the best-fit model used to describe the in vitro release performance of warfarin sodium with 50-100 rpm and the USP basket and paddle apparatuses. Significant differences in all calculated parameters were found (*P<0.05) excepting percent dissolved at 30 min with 0.1 N hydrochloric acid and phosphate buffer pH 6.8.
Conclusion: More research is necessary to identify the in vitro release performance of poorly soluble drugs under available USP apparatuses considering factors as agitation rate and kind of dissolution media. The knowledge of the in vitro release performance of reference drug products is important for the design of better generic formulations
World Health Organization. Warfarin Health and Safety Guide, No. 96, Genova; 1995. Available from: http://inchem.org/ documents/hsg/hsg/hsg096.htm [Last accessed on 22 Sep 2020]
Hanley JP. Warfarin reversal. J Clin Pathol 2004;57:1132−9.
Arif KM, Rahman MA. A review of warfarin dosing and monitoring. Faridpur Med Coll J 2018;13:40−3.
Drug Delivery Foundation. Biopharmaceutics classification system (BCS) database. Available from: http://www.ddfint.org/bcs-about. [Last accessed on 22 Sep 2020]
United States Pharmacopeia and National Formulary USP 43-NF38: The United States Pharmacopeial Convention, Inc: Rockville MD; 2020.
Gao Z. In vitro dissolution testing with flow-through method: a technical note. AAPS PharmSciTech 2009;10:1401−5.
Missaghi S, Fassihi R. Release characterization of dimenhydrinate from an eroding and swelling matrix: selection of appropriate dissolution apparatus. Int J Pharm 2005;293:35−42.
Wu Y, Kildsig DO, Ghaly ES. Effect of hydrodynamic environment on tablets dissolution rate. Pharm Dev Technol 2004;9:35−7.
ICH. Harmonised Tripartite Guideline. Q2B Validation of Analytical Procedures: Methodology. International Conference on Harmonization; 1996. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q2b-validation-analytical-procedures-methodology. [Last accessed on 22 Sep 2020]
Yuksel N, Kanik AE, Baykara T. Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and independent-methods. Int J Pharm 2000;209:57−67.
Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DD Solver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J 2010;12:263−71.
Shabir GA. Evaluation of USP basket and paddle dissolution methods using different generic atenolol tablets. Turk J Pharm Sci 2011;8:253−60.
Chevalier E, Viana M, Artaud A, Chomette L, Haddouchi S, Devidts G, et al. Comparison of three dissolution apparatuses for testing calcium phosphate pellets used as ibuprofen delivery systems. AAPS PharmSciTech 2009;10:597−605.
Jinno J, Kamada N, Miyake M, Yamada K, Mukai T, Odomi M, et al. In vitro-in vivo correlation for wet-milled tablet of poorly water-soluble cilostazol. J Controlled Release 2008;130:29−37.
Jantratid E, De Maio V, Ronda E, Mattavelli V, Vertzoni M, Dressman JB. Application of biorelevant dissolution tests to the prediction of in vivo performance of diclofenac sodium from an oral modified-release pellet dosage form. Eur J Pharm Sci 2009;37:434−41.
Adams E, Coomans D, Smeyers Verbeke J, Massart DL. Non-linear mixed effects models for the evaluation of dissolution profiles. Int J Pharm 2002;240:37−53.
Khamanga SM, Parfitt N, Nyamuzhiwa T, Haidula H, Walker RB. The evaluation of Eudragit microcapsules manufactured by solvent evaporation using USP apparatus 1. Dissolut Technol 2009;16:15−22.
Ilango KB, Kavimani S. A systematic review of mathematical models of pharmaceutical dosage forms. Int J Curr Pharm Rev Res 2015;6:59−70.
Arafat M, Ahmed Z, Arafat O. Comparison between generic drugs and brand name drugs from bioequivalence and thermoequivalence prospective. Int J Pharm Pharm Sci 2017;9:1−4.
Sornsuvit C, Niamhun N, Luengpiansamut N, Sangsrijan S, Niwatananum W, Kaewvichit S, et al. Pharmacokinetics and bioequivalence studies of warfarin sodium 5 milligrams tablet in healty thai subjects. Int J Pharm Pharm Sci 2015;7:219−22.
Basha A, Ambika, Kareem A, Sumithra M. Novel anticoagulants beyond heparin and warfarin. Asian J Pharm Clin Res 2018;11:15−8.