FORMULATION AND OPTIMIZATION OF FLOATING TABLETS OF CLOPIDOGREL BISULPHATE USING DESIGN OF EXPERIMENTS

Sanjeevani S. Deshkar; Arvind S. Pawara; Satish V. Shirolkar

doi:10.22159/ijap.2018v10i6.27873

Authors

Sanjeevani S. Deshkar Department of pharmaceutics, Dr. D. Y. Patil institute of pharmaceutical sciences and research, Pimpri, Pune, India - 411018
Arvind S. Pawara Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India - 411018
Satish V. Shirolkar Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India - 411018

DOI:

https://doi.org/10.22159/ijap.2018v10i6.27873

Keywords:

Clopidogrel bisulphate, Antiplatelet drug, Floating tablet, Design of experiment, Factorial design, Gastroretentive drug delivery

Abstract

Objective: The present study aimed at designing of floating matrix tablet of clopidogrel bisulphate by design of experiments.

Methods: The tablets were prepared by direct compression technique using hydroxypropyl methylcellulose K15 (HPMC) as a matrix polymer and sodium bicarbonate as a gas generating agent. In order to optimize the concentration of HPMC (X₁) and sodium bicarbonate (X₂), a 3² full factorial design was employed. The tablet formulations were evaluated for floating lag time (Y₁), floating or buoyancy time (Y₂), percent water uptake, and differential scanning calorimetry (DSC) and in vitro drug release (Y₃).

Results: The formulation variables, HPMC concentration, and sodium bicarbonate concentration exerted a significant effect on floating behavior and drug release characteristics of the tablet. The optimized formulation, with 15% sodium bicarbonate concentration and 30 % HPMC concentration resulted in 5Â±2.6 sec of floating lag time, 22.0Â±0.6 h of floating time and 42.0Â±0.99% of clopidogrel bisulphate release in 8 h of dissolution study. The drug release mechanism was identified as nonfickian. The water uptake studies revealed that with an increase in HPMC concentration, there was an increase in swelling index of tablet whereas higher sodium bicarbonate concentration supported the faster erosion of matrix tablets. DSC study revealed no interaction of drug and polymers. The lower percentage error between predicted and observed responses of the optimized formulation validated the design.

Conclusion: The study demonstrated successful designing of floating clopidogrel bisulphate tablet with factorial design.

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References

Hou Y, Carrim N, Wang Y, Gallant R, Marshall A, Ni H. Platelets in hemostasis and thrombosis: novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis. J Biomed Res 2015;29:437-44.

Altman R. Risk factors in coronary atherosclerosis athero-inflammation: the meeting point. Thromb J 2003;1:4-4.

Bray PF. Platelet hyperreactivity: predictive and intrinsic properties. Hematol/Oncol Clin North Am 2007;21:633-6.

Krishnan MN, Zachariah G, Venugopal K, Mohanan PP, Harikrishnan S, Sanjay G, Jeyaseelan L, et al. Prevalence of coronary artery disease and its risk factors in Kerala, south India: a community-based cross-sectional study. BMC Cardiovasc Disord 2016;16:12.

Nag T, Ghosh A. Cardiovascular disease risk factors in Asian Indian population: a systematic review. J Cardiovasc Dis Res 2013;4:222-8.

Periayah MH, Halim AS, Saad AZ. Mechanism action of platelets and crucial blood coagulation pathways in hemostasis. Int J Hematol Oncol Stem Cell Res 2017;11:319-27.

Sambu N, Curzen N. Monitoring the effectiveness of antiplatelet therapy: opportunities and limitations. Br J Clin Pharmacol 2011;72:683-96.

Shifrin MM, Widmar SB. Platelet inhibitors. Nurs Clin North Am 2016;51:29-43.

Creager MA. Results of the CAPRIE trial: efficacy and safety of clopidogrel. Clopidogrel versus aspirin in patients at risk of ischaemic events. Vasc Med 1998;3:257-60.

Eikelboom JW, Hirsh J, Spencer FA, Baglin TP, Weitz JI. Antiplatelet drugs: antithrombotic therapy and prevention of thrombosis. Chest 2012;141 Suppl 2:e89s-e119s.

Huang Z, Francis R, Aubry A, Steckbeck A, Sciascia D. Development of a single in vitro dissolution method for a combination trilayer tablet formulation of clopidogrel and pravastatin. Dissolution Technol 2011;12-9. Doi.org/ 10.14227/DT180111P12

Ugurlu T, Rayaman E, Karacicek U. Optimization and evaluation of clarithromycin floating tablets using experimental mixture design. Acta Pol Pharm 2014;71:311-21.

Sreejan Manna KJ, Kancherla RA, Lakshmi KK. Alginate-based gastro-retentive raft forming tablets for enhanced bioavailability of Tinidazole. Int J Appl Pharm 2017;9:16-21.

Pawar VK, Kansal S, Garg G, Awasthi R, Singodia D, Kulkarni GT. Gastroretentive dosage forms: a review with special emphasis on floating drug delivery systems. Drug Delivery 2011;18:97-110.

Velivela S, Vinyas M, Pati N. Formulation and in vitro evaluation of Ritonavir floating tablets by melt granulation technique. Int J Appl Pharm 2016;8:12-5.

Kumar R, Chandra A. Formulation and evaluation of famotidine micro balloons with enhanced anti-ulcer activity. Int J Appl Pharm 2018;10:131-40.

Deshkar SS, Pore AR. Formulation and optimization of immediate release pellets of antiplatelet drugs using the design of experimentation. J Drug Delivery Sci Technol 2017;7:255-68.

Gharti KP, Thapa P, Budhathoki U, Bhargava A. Formulation and in vitro evaluation of floating tablets of hydroxypropyl methylcellulose and polyethylene oxide using ranitidine hydrochloride as a model drug. J Young Pharm 2012;4:201-8.

Arza RA, Gonugunta CS, Veerareddy PR. Formulation and evaluation of swellable and floating gastroretentive ciprofloxacin hydrochloride tablets. AAPS PharmSciTech 2009;10:220-6.

Deshkar S, Pawar M, Shirsat A, Shirolkar S. Development of sustained release tablet of Mebeverine hydrochloride. J Pharm Educ Res 2013;4:64-9.

Rao KR, Lakshmi KR. Design, development and evaluation of clopidogrel bisulfate floating tablets. Int J Pharm Investig 2014;4:19-26.