Development of metformin HCl granules using brown flaxseed mucilage as a retardant polymer
effects of polymer and drug ratio
Keywords:Extended-release granules, Flaxseed mucilage, Metformin HCl
Flaxseed (Linum usitatissimum L.) is the seed of a multipurpose plant of pharmaceutical interest, as its mucilage can be used as a natural matrix to develop extended-release dosage forms and potentially replace synthetic polymers. In this study, a 3² factorial design with two replicates of the central point was applied to optimize the development of extended-release granules of metformin HCl. The total fiber content of the mucilage as well as the friability and dissolution of the formulations were evaluated. The lyophilized mucilage presented a high total fiber content (42.63%), which suggests a high efficiency extraction process. Higher concentrations of the mucilage and metformin HCl yielded less friable granules. In addition, lower concentrations of metformin HCl and higher concentrations of the mucilage resulted in slower drug release during the dissolution assays. The release kinetics for most formulations were better represented by the Hixson-Crowell model, while formulations containing a higher concentration of the mucilage were represented by the Korsmeyer-Peppas model. Nonetheless, five formulations showed a longer release than the reference HPMC formulation. More desirable results were obtained with a higher concentration of the mucilage (13-18%) and a lower concentration of metformin (40%).
AOAC, Official methods of AOAC International: Official Method 993.21. 18th ed. Gaithersburg, MD: AOAC International; 2005.
Barroso AKM, Torres AG, Castelo-Branco VN, Ferreira A, Finotelli PV, Freitas SP, et al. Brown and golden flaxseed: chemical and functional properties of the seeds and the cold-pressed oils. Cienc Rural. 2014;44(1):181-188.
Brazil. Farmacopeia brasileira. 6th ed. Brasília: Agência Nacional de Vigilância Sanitária; 2019.
Brazil. Tabela brasileira de composição de alimentos - TACO. 4th ed. Campinas: Universidade Estadual de Campinas; 2011.
Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123-133.
Cui W, Mazza G, Oomah BD, Biliaderis CG. Optimization of an aqueous extraction process for flaxseed gum by response surface methodology. LWT-Food Sci Technol. 1994;27(4):363-369.
Eichie FE, Kudehinbu AO. Effect of particle size of granules on some mechanical properties of paracetamol tablets. Afr J Biotechnol. 2009;8(21).
Ghumman SA, Noreen S, tul Muntaha S. Linum usitatissimum seed mucilage-alginate mucoadhesive microspheres of metformin HCl: Fabrication, characterization and evaluation. Int J Biol Macromol. 2020;155:358-368.
Gouda R, Baishya H, Qing Z. Application of mathematical models in drug release kinetics of carbidopa and levodopa ER tablets. J Dev Drugs. 2017;6(2):1-8.
Goyal A, Sharma V, Upadhyay N, Gill S, Sihag M. Flax and flaxseed oil: an ancient medicine & modern functional food. J Food Sci Technol. 2014;51(9):1633-1653.
Gryczová E, Dvořáčková K, Rabišková M. Evaluation of pellet friability. Ceska Slov Farm. 2009;58:9-13.
Hasnain MS, Rishishwar P, Rishishwar S, Ali S, Nayak AK. Isolation and characterization of Linum usitatisimum polysaccharide to prepare mucoadhesive beads of diclofenac sodium. Int J Biol Macromol . 2018;116:162-172.
Kaewmanee T, Bagnasco L, Benjakul S, Lanteri S, Morelli CF, Speranza G, et al. Characterisation of mucilages extracted from seven Italian cultivars of flax. Food Chem. 2014;148:60-69.
Keleb EI, Vermeire A, Vervaet C, Remon JP. Continuous twin screw extrusion for the wet granulation of lactose. Int J Pharm. 2002;239(1):69-80.
Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol. 1975;27(1):48-49.
MacFadyen J. Flax Americana: a history of the fibre and oil that covered a continent. 3rd ed. Quebec: McGill-Queen’s University Press; 2018.
Marks AM, Sciarra JJ. Effect of size on other physical properties of granules and their corresponding tablets. J Pharm Sci. 1968;57(3):497-504.
Mittapalli O, Rowland G. Inheritance of seed color in flax. Crop Sci. 2003;43(6):1945-1951.
Monteyne T, Vancoillie J, Remon JP, Vervaet C, De Beer T. Continuous melt granulation: Influence of process and formulation parameters upon granule and tablet properties. Eur J Pharm Biopharm. 2016;107:249-262.
Nayak AK, Pal D. Blends of jackfruit seed starch-pectin in the development of mucoadhesive beads containing metformin HCl. Int J Biol Macromol . 2013a;62:137-145.
Nayak AK, Pal D. Formulation optimization and evaluation of jackfruit seed starch-alginate mucoadhesive beads of metformin HCl. Int J Biol Macromol . 2013b;59:264-272.
Nayak AK, Pal D, Das S. Calcium pectinate-fenugreek seed mucilage mucoadhesive beads for controlled delivery of metformin HCl. Carbohydr Polym. 2013c;96(1):349-357.
Nayak AK, Pal D, Pradhan J, Hasnain MS. Fenugreek seed mucilage-alginate mucoadhesive beads of metformin HCl: Design, optimization and evaluation. Int J Biol Macromol . 2013d;54:144-154.
Nayak Ak, Pal D, Santra K. Artocarpus heterophyllus L. seed starch-blended gellan gum mucoadhesive beads of metformin HCl. Int J Biol Macromol . 2014a;65:329-339.
Nayak AK, Pal D, Santra K. Development of pectinate-ispagula mucilage mucoadhesive beads of metformin HCl by central composite design. Int J Biol Macromol . 2014b;66:203-211.
Nayak AK, Pal D, Santra K. Ispaghula mucilage-gellan mucoadhesive beads of metformin HCl: Development by response surface methodology. Carbohydr Polym . 2014c;107:41-50.
Nayak Ak, Pal D, Santra K. Tamarind seed polysaccharide-gellan mucoadhesive beads for controlled release of metformin HCl. Carbohydr Polym . 2014d;103:154-163.
Rocha MS, Rocha LCS, Viçosa AL, Guimarães TF, Marotta PLLS, Ferreira CE, et al. Developing and Featuring Matrix Tablets by Using Gross Linseed Mucilage as a Retardant Polymer. J Pharm Innov. 2021a;1-13.
Rocha MS, Rocha LCS, Viçosa AL, Feijó MBS, Marotta PLLS, Mourão SC. Multiobjective optimization of the flaxseed mucilage extraction process using normal-boundary intersection approach. Br Food J. 2021b.
Soukoulis C, Gaiani C, Hoffmann L. Plant seed mucilage as emerging biopolymer in food industry applications. Curr Opin Food Sci. 2018;22:28-42.
Thakur G, Mitra A, Pal K, Rousseau D. Effect of flaxseed gum on reduction of blood glucose and cholesterol in type 2 diabetic patients. Int J Food Sci Nutr. 2009;60(6):126-136.
Van Melkebeke B, Vervaet C, Remon JP. Validation of a continuous granulation process using a twin-screw extruder. Int J Pharm . 2008;356(1):224-230.
Vittori N. Method of isolating mucilaginous polysaccharides and uses thereof. (Washington, DC: U.S. Patent No. 6482942B1). U.S. Patent and Trademark Office. 2002.
Western TL. The sticky tale of seed coat mucilages: production, genetics, and role in seed germination and dispersal. Seed Sci Res. 2012;22(1):1-25.
Yadav IK, Jain DA. Formulation and evaluation of diclofenac sodium SR tablets using Linum usitatissimum seed mucilage Matrixing. Indian J Res Pharm Biotech. 2015;3(5):367.
Ziolkovska A. Laws of flaxseed mucilage extraction. Food Hydrocoll. 2012;26(1):197-204.
How to Cite
Copyright (c) 2023 Brazilian Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on line journal has open and free access.
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Grant numbers 001
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
Grant numbers E-26/211.582/ 2021