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A strategic design improvement in patient-centric sustained delivery of metoprolol succinate using natural gum blend matrix: design, development and in-vitro comparative evaluation

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Abstract

The aim of this study is to design and evaluate metoprolol succinate sustained release (SR) matrix tablets employing a natural gum blend as the rate-retarder. Develo** a tablet matrix utilizing locust bean gum (LBG), xanthan gum (XG), and guar gum (GG) was done to aid metoprolol succinate release over a 24-h period and help in once-daily dosage, reducing nocturnal episodes in hypertensive patients. In an effort to create a synergistic effect, attempts were made to combine commonly used natural gums, XG and GG, with LBG, which served as the primary release-retardant. The optimal way to formulate the tablet was studied using polymer blend ratios of 1:1, 1:3, 1:5, 1:1:1, 1:2:1 and 1.5:1.5:1. The same created polymer mix was used as the binding agent to prepare tablets utilizing the wet granulation process. Weight, thickness, hardness, content homogeneity, in-vitro drug release, erosion, and water uptake were used to characterize the formulations. Additional testing for drug-excipient compatibility was conducted. It was discovered that an XG:LBG:GG ratio of 1:2:1 produced the best outcomes having the highest t75% of cumulative drug release of 15.2 h, outperforming commercial formulations. A relation between the gum concentration and release rate retarding effect was also established. 3.33% of gum concentration showed optimal sustained release effects. The results concluded that the prepared SR metoprolol succinate tablets might be one of the best formulation for hypertensive patients that not only serves therapeutic purpose but also values the patients concern of providing minimal side-effect in the long run use of the medication.

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Abbreviations

LBG:

Locust bean gum

GG:

Guar gum

XG:

Xanthan gum

SR:

Sustained release

BCS:

Biopharmaceutical Classification System

References

  1. Bonow RO, Mann DL, Zipes DP, Libby P (2011) Braunwald's heart disease e-book: A textbook of cardiovascular medicine. Elsevier Health Sciences

  2. Bubnova MG (2022) Current guidelines for β-adrenoblockers use in cardiovascular diseases: focus on metoprolol succinate CR/XL: A review. CardioSomatics 13(1):51–62

    Article  Google Scholar 

  3. Sharma G, Bhurat M, Shastry V, Shrivastava B (2022) Design and development of metoprolol succinate sustained release tablet using Eulophia herbacae and Remusatia vivipara tuber mucilage as novel drug release modifiers. Mater Technol 37(9):1040–1050

    Article  CAS  Google Scholar 

  4. Vinereanu D, Spinar J, Pathak A, Kozlowski D (2020) Role of metoprolol succinate in the treatment of heart failure and atrial fibrillation: a systematic review. Am J Ther 27(2):e183–e193

    Article  PubMed  Google Scholar 

  5. Tong X, Pan W, Su T, Zhang M, Dong W, Qi X (2020) Recent advances in natural polymer-based drug delivery systems. React Funct Polym 148:104501

    Article  CAS  Google Scholar 

  6. Flügel K, Hennig R, Thommes M (2020) Impact of structural relaxation on mechanical properties of amorphous polymers. Eur J Pharm Biopharm 154:214–221

    Article  PubMed  Google Scholar 

  7. Gomes-Filho MS, Oliveira FA, Barbosa MAA (2022) Modeling the diffusion-erosion crossover dynamics in drug release. Phys Rev E 105(4):044110

    Article  CAS  PubMed  Google Scholar 

  8. Bermejo M, Sanchez-Dengra B, Gonzalez-Alvarez M, Gonzalez-Alvarez I (2020) Oral controlled release dosage forms: dissolution versus diffusion. Expert Opin Drug Deliv 17(6):791–803

    Article  CAS  PubMed  Google Scholar 

  9. Amiri MS, Mohammadzadeh V, Yazdi MET, Barani M, Rahdar A, Kyzas GZ (2021) Plant-based gums and mucilages applications in pharmacology and nanomedicine: a review. Molecules 26(6):1770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dybka-Stępień K, Otlewska A, Góźdź P, Piotrowska M (2021) The renaissance of plant mucilage in health promotion and industrial applications: A review. Nutrients 13(10):3354

    Article  PubMed  PubMed Central  Google Scholar 

  11. Brassesco ME, Brandao TR, Silva CL, Pintado M (2021) Carob bean (Ceratonia siliqua L.): A new perspective for functional food. Trends Food Sci Technol 114:310–322

    Article  CAS  Google Scholar 

  12. Glicksman M (ed) (2020) Food hydrocolloids (vol. 3). Crc Press

  13. Jadav M, Pooja D, Adams DJ, Kulhari H (2023) Advances in xanthan gum-based systems for the delivery of therapeutic agents. Pharmaceutics 15(2):402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dalei G, Das S (2022) Carboxymethyl guar gum: A review of synthesis, properties and versatile applications. Eur Polym J 111433

  15. Salamone JC (2020) Polymeric materials encyclopedia. CRC Press

    Book  Google Scholar 

  16. Mandal S, Hwang S, Shi SQ (2022) Guar gum, a low-cost sustainable biopolymer, for wastewater treatment: A review. Int J Biol Macromol

  17. Petitjean M, Isasi JR (2022) Locust bean gum, a vegetable hydrocolloid with industrial and biopharmaceutical applications. Molecules 27(23):8265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Soumya RS, Raghu KG, Abraham A (2022) Locust bean gum–a potential drug delivery carrier. Polysaccharide-based Biomaterials: Delivery of Therapeutics and Biomedical Applications 13:247

    Article  Google Scholar 

  19. Cortez-Trejo MC, Gaytán-Martínez M, Reyes-Vega ML, Mendoza S (2021) Protein-gum-based gels: Effect of gum addition on microstructure, rheological properties, and water retention capacity. Trends Food Sci Technol 116:303–317

    Article  CAS  Google Scholar 

  20. Başyiğit B, Altun G, Yücetepe M, Karaaslan A, Karaaslan M (2023) Locust bean gum provides excellent mechanical and release attributes to soy protein-based natural hydrogels. Int J Biol Macromol 231:123352

    Article  PubMed  Google Scholar 

  21. Guru PR, Kar RK, Nayak AK, Mohapatra S (2023) A comprehensive review on pharmaceutical uses of plant-derived biopolysaccharides. Int J Biol Macromol 123454

  22. Basharat Z, Afzaal M, Saeed F, Islam F, Hussain M, Ikram A, Awuchi CG (2023) Nutritional and functional profile of carob bean (Ceratonia siliqua): A comprehensive review. Int J Food Properties 26(1):389–413

    Article  Google Scholar 

  23. Wang B, Sun X, **ang J, Guo X, Cheng Z, Liu W, Tan S (2022) A critical review on granulation of pharmaceuticals and excipients: Principle, analysis and typical applications. Powder Technol 401:117329

    Article  CAS  Google Scholar 

  24. The United States Pharmacopoeia Convention. USP 43–NF 38 (2019) The United States Pharmacopoeia Convention: Rockville. MD, USA

    Google Scholar 

  25. Al-Hashemi HMB, Al-Amoudi OSB (2018) A review on the angle of repose of granular materials. Powder Technol 330:397–417

    Article  Google Scholar 

  26. Kaleem MA, Alam MZ, Khan M, Jaffery SHI, Rashid B (2021) An experimental investigation on accuracy of Hausner Ratio and Carr Index of powders in additive manufacturing processes. Met Powder Rep 76:S50–S54

    Google Scholar 

  27. Moravkar KK, Shah DS, Magar AG, Bhairav BA, Korde SD, Ranch KM, Chalikwar SS (2022) Assessment of pharmaceutical powders flowability and comparative evaluation of lubricants on development of gastro retentive tablets: An application of powder flow tester. J Drug Deliv Sci Technol 71:103265

    CAS  Google Scholar 

  28. Tan BX, Foo WC, Chow KT, Gokhale R (2021) Advances in Wet granulation of modern drugs. In: Handbook of Pharmaceutical Granulation Technology (pp 283–306). CRC Press

  29. The United States Pharmacopoeia Convention. USP 905 (2011) The United States Pharmacopoeia Convention: Rockville. MD, USA

    Google Scholar 

  30. Novick S, Hudson-Curtis B (2020) Content Uniformity Testing. In: Bayesian Methods in Pharmaceutical Research (pp 407–420). Chapman and Hall/CRC

  31. Wade A, Reynolds JE (1977) Ed. Martindale: the extra pharmacopoeia 154–156

  32. Nsengiyumva EM, Alexandridis P (2022) Xanthan gum in aqueous solutions: Fundamentals and applications. Int J Biol Macromol

  33. Council of Experts, United States Pharmacopeial Convention (2010) Food Ingredient Expert Committee. Food Chemicals Codex. US Pharmacopeia Conv

  34. Bampidis V, Azimonti G, Bastos MD, Christensen H, Dusemund B, Durjava MF, Kouba M, López-Alonso M, López Puente S, Marcon F (2022) Safety and efficacy of a feed additive consisting of locust bean gum for all animal species (Dupont Nutrition and Health). EFSA J 20(8):e07435

    PubMed  PubMed Central  Google Scholar 

  35. Elella MHA, Goda ES, Gab-Allah MA, Hong SE, Pandit B, Lee S, Yoon KR (2021) Xanthan gum-derived materials for applications in environment and eco-friendly materials: A review. J Environ Chem Eng 9(1):104702

    Article  Google Scholar 

  36. Laxminarayan Joshi, Cmax Technologies Inc (2015) Sustained release metoprolol succinate, United States patent US9561187B1. https://patents.google.com/patent/US9561187B1/en

  37. Jain G, Kondapaturu G, Bhadra U (2006) Bio intellectual property services ,Extended release compositions of metoprolol succinate, United States patent US20070053983A1. https://patents.google.com/patent/US20070053983A1/en

  38. Varshi R, Jain V, Pal P, Gehalot N (2022) Formulation and evaluation of extended release gastroretentive tablets of metroprolol succinate. J Drug Deliv Ther 12(5-S):127–132

    Article  CAS  Google Scholar 

  39. Tuyen NTL, Nghiem LQ, Tuan ND, Le PH (2021) Development of a scalable process of film-coated bi-layer tablet containing sustained-release metoprolol succinate and immediate-release amlodipine besylate. Pharmaceutics 13(11):1797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zidan A, Kotamarthy L, Ramachandran R, Ashraf M, O’Connor T (2022) Optimization of screw design for continuous wet granulation: A Case Study of metoprolol succinate ER tablets. Int J Pharm 623:121964

    Article  CAS  PubMed  Google Scholar 

  41. Thombre N, Aher A, Shimpi P (2020) Formulation development and evaluation of gum Damar based sustained release matrix tablet of metoprolol succinate. Asian J Pharm Res Dev 8(3):81–86

    Article  CAS  Google Scholar 

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Acknowledgements

The authors appreciate the gift sample of Metoprolol succinate from Dr. Reddy’s Laboratories, Maharashtra, India. The authors are grateful to the Department of Pharmaceutical Technology and Department of Metallurgical and Material Engineering, Jadavpur University, Kolkata-700032 for providing with the required facilities to carry out this research work. The authors acknowledge the Department of Chemistry, Kumaun University, Nainital-263002 for carrying out DSC analysis.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Jadavpur University, 132 Raja SC Mallick Road, West Bengal, Kolkata, 700032, India

    Naureen Afrose, Rideb Chakraborty & Ketousetuo Kuotsu

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  1. Naureen Afrose
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  2. Rideb Chakraborty
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  3. Ketousetuo Kuotsu
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Contributions

Conceptualization, Naureen Afrose; Methodology, Naureen Afrose; Software, Rideb Chakraborty.; Validation, Naureen Afrose, Rideb Chakraborty and Ketousetuo Kuotsu; Formal Analysis, Naureen Afrose, Rideb Chakraborty; Investigation, Naureen Afrose; Resources, Ketousetuo Kuotsu; Data Curation, Naureen Afrose, Rideb Chakraborty; Writing – Original Draft Preparation, Naureen Afrose; Writing – Review & Editing, Naureen Afrose; Visualization, Naureen Afrose, Rideb Chakraborty; Supervision, Ketousetuo Kuotsu; Project Administration, Naureen Afrose, Rideb Chakraborty and Ketousetuo Kuotsu.

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Correspondence to Ketousetuo Kuotsu.

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Afrose, N., Chakraborty, R. & Kuotsu, K. A strategic design improvement in patient-centric sustained delivery of metoprolol succinate using natural gum blend matrix: design, development and in-vitro comparative evaluation. J Polym Res 30, 367 (2023). https://doi.org/10.1007/s10965-023-03757-9

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