FORMULATION DEVELOPMENT AND STABILITY INDICATING HPLC ASSAY OF TABLETS OF APIXABAN
DOI:
https://doi.org/10.22159/ijpps.2017v9i10.20343Keywords:
Apixaban, Formulation Development, Tablets, RP-HPLC, Stability indicating assay method, Method validationAbstract
Objective: Cost effective formulation development and stability indicating HPLC method for estimation of apixaban in bulk and tablets dosage form.
Methods: 32 factorial design was applied to formulate the immediate release tablets of apixaban by using direct compression method. The chromatographic separation was performed on Purospher Star RP-18e (5 µm, 250x4, 6 mm) column and a stability indicating assay method was developed by using HPLC. The mobile phase consists of water: acetonitrile (60:40 v/v) was delivered at a flow rate of 1 ml/min and UV detection at 280 nm. The method was validated with forced degradation studies as per ICH guidelines.
Results: Prepared batches were evaluated for all pre-compression parameters and post-compression parameters. Formulation batch F5 prepared by direct compression shows highest dissolution release of 90.97 % over the period of 60 min while disintegration time was found to be 136 seconds. The retention time of developed HPLC method was found to be 5.66 min. This method was found to be linear in a concentration range of 5-30 μg/ml of the drug (r2= 0.999). The low value of % RSD in the precision study indicates reproducibility of the method. The low value of LOD and LOQ suggests the sensitivity of the method. The results of forced degradation studies indicated that the drug was less stable in thermal and photolytic condition and degraded in acidic, basic, oxidative conditions.
Conclusion: On the basis of formulation evaluation, batch F5 was found to be promising formulation suitable for the immediate release of apixaban. Results obtained by validation studies suggested that the developed stability indicating assay method is simple, accurate, specific, sensitive and precise. Thus, this method can be used for routine analysis of apixaban formulation and to check the stability testing.
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Pinto DJ, Orwat MJ, Koch S, Rossi KA, Alexander RS, Smallwood A, Wong PC, et al. Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl) phenyl)-4, 5, 6, 7-tetrahydro-1 H-pyrazolo [3, 4-c] pyridine-3-carboxamide (Apixaban, BMS-562247), a highly potent, selective, efficacious and orally bioavailable inhibitor of blood coagulation factor Xa. J Med Chem 2007;50:5339-56.
Lassen MR, Davidson BL, Gallus A, Pineo G, Ansell J, Deitchman D. The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. J Thromb Haemostasis 2007;5:2368-75.
FDA approves apixaban for stroke prevention in nonvalvular AF-Medscape; 2012. p. 28.
Landge SB, Jadhav SA, Dahale SB, Solanki PV, Bembalkar SR, Mathad VT. Development and validation of stability indicating RP-HPLC method on core-shell column for determination of degradation and process related impurities of the apixaban-an anticoagulant drug. Am J Anal Chem 2015;6:539-50.
Prabhune SS, Jaguste RS, Kondalkar PL, Pradhan NS. Stability-indicating high-performance liquid chromatographic determination of apixaban in presence of degradation products. Sci Pharm 2014;82:777-85.
Katta R, Nagaraju C, Ramashrinivas, Rao GN. Two novel validated RP-HPLC and UV spectrophotometric methods for estimation of apixaban in bulk and pharmaceutical dosage forms. Am J PharmTech Res 2015;5:4.
Zhang W, Lou D, Zhang D, Zhang Y, Huang H. ‘Determination of rivaroxaban, apixaban and edoxaban in rat plasma by UPLC–MS/MS method. J Thromb Thrombolysis 2016;42:205–11.
Schmitz E, Boonen K, van den Heuvel D, van Dongen J, Schellings M, Emmen J, et al. Determination of dabigatran, rivaroxaban and apixaban by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and coagulation assays for therapy monitoring of novel direct oral anticoagulants. J Thromb Haemost 2014;12:1636-46.
Delavenne X, Mismetti P, Basset T. Rapid determination of apixaban concentration in human plasma by liquid chromatography/tandem mass spectrometry: application to pharmacokinetic study. J Pharm Biomed Anal 2013;78-79:150–3.
Èšilea I. Determination of apixaban levels in human plasma by a high-throughput liquid chromatographic tandem mass spectrometry assay. Rev Romana Med Lab 2015;23. https://doi.org/10.1515/rrlm-2015-0006
Tantawy MA, El-Ragehy NA, Hassan NY, Abdelkawy M. Stability-indicating spectrophotometric methods for determination of the anticoagulant drug apixaban in the presence of its hydrolytic degradation product. Spectrochim Acta Mol Biomol Spectrosc 2016;159:13–20.
Sutradhar KB, Akhter DT, Uddin R. Formulation and evaluation of taste masked oral dispersible tablets of domperidone using sublimation method. Int J Pharm Pharm Sci 2012;4:727-32.
Rath S, Gupta BK, Bala NN, Dhal HC. Formulation and optimization of immediate release telmisartan tablets using full factorial design. Int J Appl Pharm 2011;3:20-4.
India Pharmacopoeia, Ministry of Health and Family Welfare, New Delhi; Govt. of India, Controller of Publications; 2007. p. 177-83.
United States of Pharmacopeia-National Formulary. USP 30–NF-25. The United States Pharmacopeial Convention, Rockville, MD; 2007;1:644, 242, 645, 731, 634.
Sree Giri Prasad B, Gupta VRM, Devanna N, Rama Devi M, Tamilselvan A, Siva Subramanian N. Formulation and evaluation of clopidogrel bisulfate Immediate release tablets. J Global Trends Pharm Sci 2014;5:2154-66.
ICH Harmonized-Tripartite Guidelines, Stability Testing of New Drug Substance And Products, Q1A (R2); 2003.
Naazneen S, Sridevi A. Development of assay method and forced degradation study of valsartan and sacubitril by RP-HPLC in tablet formulation. Int J Appl Pharm 2017;9:9-15.
Jain HK, Gujar KN, Randhe VA. Stability indicating RP-HPLC assay method for estimation of midodrine hydrochloride in bulk and tablets. Int J Pharm Pharm Sci 2016;8:283-7.
Bakshi M, Singh S. Development of validated stability-indicating assay methods-critical review. J Pharm Biomed Anal 2002;28:1011-40.
Jain HK, Ranjale AR. Development and validation of a RP-HPLC method for simultaneous estimation of cefoperazone and tazobactam in the marketed formulation. Int J Pharm Pharm Sci 2014;6:462-5.
Devkare PN, Jain HK. Development and validation of a RP-HPLC method for simultaneous estimation of S(-) amlodipine besylate and clopidogrel bisulphate in tablet dosage form. Int J Pharm Pharm Sci 2013;5:770-5.
ICH Harmonized-Tripartite Guidelines, Validation of Analytical Procedure: Text and Methodology Q2(R1); 2005.
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