FLOATING MULTIPLE UNIT MINITABLETS OF METOPROLOL SUCCINATE: FORMULATION, IN VITRO AND IN VIVO CHARACTERIZATION
Objective: In this present research, formulation of floating multiple unit minitablets of metoprolol succinate without using gas generating agent was attempted with an objective of increased residence time, sustain release and improved oral bioavailability.
Materials and Methods: Solid dispersions were prepared with lipophilic carriers such as compritol ATO888, Gelucire 43/01, Gelucire 39/01 and precirol ATO05 was formulated using fusion technique. Neusillin US2 was used as an adsorbent. The solid dispersions were compressed into minitablets each weighing 20 mg and then filled into ‘0’ size capsule.
Results: Formulation F9, F10, F14 and F15 showed instantaneous floating lag time i.e. 0 min, floating time more than 12 h and sustained release upto 12 h. Pharmacokinetic study of the optimized formulation (F9) showed 2.46 times increase in area under the curve with increased residence time.
Conclusion: Hence gelucire 43/01 based floating multiple unit minitablets of metoprolol succinate can be considered as a promising approach.
1. Hoffman A. Pharmacodynamic aspects of sustained release preparations. Adv Drug Deliv Rev 1998;33(3):185-99.
2. Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug delivery systems. Expert Opin Drug Deliv 2006;3(2):217-33.
3. 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 Deliv 2011;18(2):97-110.
4. Abdul S, Chandewar AV, Jaiswal SB. A flexible technology for modified-release drugs: Multiple-unit pellet system (MUPS). J Control Release 2010; 147(1):2-16.
5. Kawashima Y, Niwa T, Takeuchi H, Hino T, Ito Y. Preparation of multiple unit hollow microspheres (microballoons) with acrylic resin containing tranilast and their drug release characteristics (in vitro) and floating behavior (in vivo). J Control Release 1991;16(3):279-89.
6. Lingam M, Ashok T, Venkateswaralu V, Rao MY. Design and evaluation of a novel matrix type multiple units as biphasic gastroretentive drug delivery systems. AAPS Pharm SciTech 2008;9(4):1253-61.
7. Panda M, Rao MEB, Patra CN, Panda J, Panigrahi KC, Patro G. Formulation and development of floating multiple-unit minitablets of nimodipine without using a gas-generating agent: in vitro and in vivo characterization. Future J Pharm Sci 2020;6(4):1-9.
8. Singh BN, Kim KH. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. J Control Release 2000;63(3): 235-59.
9. Lopes CM, Bettencourt C, Rossi A, Buttini F, Barata P. Overview on gastroretentive drug delivery systems for improving drug bioavailability. Int J Pharma 2016;510(1):144-58.
10. Benfield P, Clissold SP, Brogden RN. Metoprolol. Drugs 1986;31(5):376-29.
11. Rao GK, Mandapalli PK, Manthri R, Reddy VP. Development and in vivo evaluation of gastroretentive delivery systems for cefuroxime axetil. Saudi Pharm J 2013;21(1):53-9.
12. Kendall MJ, Maxwell SRJ, Sandberg A, Westergren G. Controlled Release Metoprolol. Clin Pharmacokinet 1991;21(5):319-30.
13. Panigrahi KC, Patra CN, Jena GK, Ghose D, Jena J, Panda SK. Gelucire: a versatile polymer for modified release drug delivery system. Future J Pharm Sci 2018;4(1):102-8.
14. Jain SK, Gupta A. Development of gelucire 43/01 beads of metformin hydrochloride for floating delivery. AAPS PharmSciTech 2009;10(4):1128-36.
15. Patel DM, Patel NM, Patel VF, Bhatt DA. Floating granules of ranitidine hydrochloride-gelucire 43/01: Formulation optimization using factorial design. AAPS PharmSciTech 2007;8(2):E25-31.
16. Jammula S, Patra CN, Swain S, Panigrahi KC, Nayak S, Dinda SC. Design and characterization of cefuroxime axetil biphasic floating minitablets. Drug Deliv 2015;22(1):125-35.
17. Zheng X, Yang R, Tang X, Zheng L. Part I: characterization of solid dispersions of nimodipine prepared by hot-melt extrusion. Drug Dev Ind Pharm 2007;33(7):791-802.
18. Fonner DE, Banker GS, Swarbrick J. Micromeritics of granular pharmaceutical solids I: physical properties of particles prepared by five different granulation methods. J Pharm Sci 1966;55(2):181-86.
19. Arora S, Ali J, Ahuja A, Khar RK, Baboota S. Floating drug delivery systems: A review. AAPS PharmSciTech 2005;6(3):E372-90.
20. Shakya R, Thapa P, Saha RN. In vitro and in vivo evaluation of gastroretentive floating drug delivery system of ofloxacin. Asian J Pharm Sci 2013;8(3):191- 8.
21. Aulton ME, Taylor K. Aulton’s pharmaceutics?: the design and manufacture of medicines. Elsevier Health Science, London. 2013.
22. Boldhane S, Kuchekar B. Development and optimization of metoprolol succinate gastroretentive drug delivery system. Acta Pharm 2010;60(4):415-25.
23. Thakkar VT, Shah PA, Soni TG, Parmar MY, Gohel MC, Gandhi TR. Goodness-of-Fit Model-Dependent Approach for Release Kinetics of Levofloxacin Hemihydrates Floating Tablet. Dissolution Technol 2009;16(1): 35-9.
24. Panigrahi KC, Jena J, Jena GK, Patra CN, Rao MEB. QBD-based systematic development of Bosentan SNEDDS: Formulation, characterization and pharmacokinetic assessment. J Drug Deliv Sci Technol 2018;47:31-42.
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