Development and evaluation of floating tablet of metoprolol succinate for increased bioavailability
Keywords:
Metoprolol succinate, floating tablet, bioavailability, hydrophilic polymers, gastroretentive drug deliveryAbstract
The present study is based on development and evaluation of gastroretentive floating tablets of metoprolol succinate by direct compression method, to increase the oral bioavailability of MS. For this, we used a combination of two different hydrophilic polymers that is polyethylene oxide PEO N-80 (X1) and hydroxyethylcellulose HEC (X2) as independent variables and studied its effect on drug release (as dependent variable) at 20h for MS. A 32 factorial design was used for optimization purpose. The DSC result shows no interaction between two polymers and the drug (MS). Further, invitro drug release studies have shown a sustained drug release for more than 20h in upper gastrointestinal region (stomach). In vivo study using rabbits have shown increased AUC0-24 (bioavailability) of prepared optimized F6 formulation as compared to the marketed sustain release tablet of MS. Stability study shows no comparable differences on physical parameters and the drug release after 3 months of accelerated stability testing. Hence, we can conclude that a floating tablet containing combination of hydrophilic polymers can be used for gastric retention for more than 20hr which will increase the oral bioavailability of MS.
References
Thomas C, Westfall D.P. Adrenergic agonists and antagonists. In: Brunton, L.L., Lazo, J.S., Parker, K.L., editors. Goodman and Gilman's. The Pharmacological Basis of Therapeutics. Eleventh ed. NY: Mc Graw-Hill. 2006, pp. 278–84. 2. Kendall, M.J, Maxwell S.R, Sandberg A, Westergren G. Controlled release metoprolol. Clinical pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 1991;21:319–30. 3. Hwang SJ, Park H, Park K. Gastric retentive drug-delivery systems. Crit Rev Ther Drug Carrier Syst.1998; 15: 243–84. 4. Jobin G, Cortot A, Godbillon J, Duval M, Schoeller JP, Hirtz J and Bernier JJ. Investigation of drug absorption from the gastrointestinal tract of man. I. Metoprolol in stomach, duodenum, and jejunum, Br. J. Clin. Pharmacol. 1985; 19: 97–105. 5. Narendra C, Srinath MS and Babu G.Optimization of bilayer floating tablet containing metoprolol tartrate as a model drug for gastric retention. AAPS PharmSciTech. 2006; 7: 23–29.DOI: 10.1208/pt070234. 6. Kendall MJ, Maxwell SR, Sandberg A and Westergren G. Controlled release metoprolol. Clinical pharmacokinetic and therapeutic implications. Clin. Pharmacokin. 1991; 21: 319–330. 7. Sanjay PB, Bhanudas SK. Development and optimization of metoprolol succinate gastroretentive drug delivery system. Acta Pharm. 2010; 60: 415–425. 8. Ashok T, Manthena MV, Chitrali MS, Pavan KC, Sriharshavardhan S. Effect of Sodium Alginate in Combination With HPMC K 100 M in Extending the Release of Metoprolol Succinate from its Gastro-Retentive Floating Tablets. Indian Journal of Pharmaceutical Education and Research.2015; 49(3): 249-258. 9. Gagan DS, Neetu K, Amarjit S, Sunil T. Formulation and in vitro evaluation of metoprolol Succinate floating tablets. Indonesian J. Pharm.2013; 24(3): 170 – 176. 10. Narendra C, Srinath MS and Babu G. Optimization of Bilayer Floating Tablet Containing Metoprolol Tartrate as a Model Drug for Gastric Retention. AAPS PharmSciTech .2006; 7(2) : Article 34. 11. Alderman D. A review of cellulose ethers in hydrophilic matrices. Int J Pharm Tech Prod Manuf, 1984, 5:1–9. 12. Jamzad S, Tutunji L, Fassihi R. Analysis of macromolecular changes and drug release from hydrophilic matrix systems. Int J Pharm. 2005; 292:75–85. 13. Varma MVS, Kaushal AM, Garg A, Garg S. Factors affecting mechanism and kinetics of drug release from matrix based oral controlled drug delivery systems. Am J Drug Deliv.2004; 2: 43–57. 14. Colombo P, Bettini R, Santi P, Ascentis AD, Peppas NA. Analysis of the swelling and release mechanisms from drug delivery systems with emphasis on drug solubility and water transport. J Control Release.1996; 39: 231–237. 15. Colombo P, Bettini R, Peppas NA. Observation of swelling processes and diffusion front position during swelling in hydroxypropyl methyl cellulose (HPMC) matrices containing a soluble drug. J Control Release.1999; 61: 83–91. 16. Melia CD. Hydrophilic matrix sustained release systems based on polysaccharide carriers. Crit Rev Ther Drug.1990; 8: 395–421. 17. Dhawan S, Varma M, Sinha V.R. High molecular weight poly (ethyleneoxide)-based drug delivery systems. Part I: hydrogels and hydrophilic matrix systems. Pharm Technol 2005; 29(5): 72–7476–80. 18. Dhawan S, Varma M, Sinha V. Applications of poly (ethylene oxide) in drug delivery systems. Part II. Pharm Technol 2005; 29(9): 82–96. 19.Deshpande RD, Gowda DV, Mohamad N, Marambar DN. Bi-LayerTablets- An Emerging Trend: A Review. International Journal of Pharmaceutical Science and Research 2011; 2 (10): 2534-44. 20. Singh BN, Kim KH. Floating drug delivery systems an approach to oral controlled drug delivery via gastric retention. J Control Rel. 2000; 63(3): 235-59 21. Leon L, Herbert LA, kanic JL. The theory and practice of industrial pharmacy, Varghese publishing house, 3rd ed; p. 293-345. 22. Remington. The Science and Practice of Pharmacy, 19th ed; p.1669-70. 23. Rosa M, Zia H, Rhodes T. Dosing and testing in vitro of a bioadhesive and floating drug delivery system for oral application. Int J. Pharm. 1994; 105(1): 65-70. 24. United States Pharmacopoeia Revision Bulletin Official August 1. National Formulary.USP Convention, Rockville; 2012. 25. Jain SK, Awasthi AM, Jain NK. Calcium silicate based microspheres of rapiglinide for gastro retentive floating drug delivery: Preparation and in vitro characterization. J. Control. Rel. 2005; 107(4): 300‐9. 26. Parakh SR, Gothoskar AV, Karad MTA. Novel method for the study of water absorption rates by swellable matrices. Pharm Tech. 2003; 5:40–8. 27. Higuchi T. Mechanism of sustained action medication. J Pharm Sci. 1963; 52: 1145–9. 28. Ritger PL, Peppas NA. A simple equation for description of solute release. I. Fickian and non-fickian release from nonswellable devices in the form slabs, spheres, cylinder or discs. J Control Release. 1987; 5 :23–36.
