The Influence of Polymer Type and Concentration on the Metoprolol Mass Transfer in Extended-Release Tablet of Metoprolol Succinate

Khadivparsi, Parissa; Rafiee-Tehrani, Morteza; Dorkoosh, Farid; Babaee Darabad, Jabber; Azizpour, Hedayat; Rezamandi, Nariman; Larki, Nadia

doi:10.22059/jchpe.2023.351673.1418

The Influence of Polymer Type and Concentration on the Metoprolol Mass Transfer in Extended-Release Tablet of Metoprolol Succinate

Document Type : Research Paper

Authors

Parissa Khadivparsi ¹

Morteza Rafiee-Tehrani ²

Farid Dorkoosh ³

Jabber Babaee Darabad ⁴

Hedayat Azizpour ¹

Nariman Rezamandi ⁵

Nadia Larki ¹

¹ School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran

² Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

³ Medical Biomaterial Research Center, Tehran University of Medical Sciences, Tehran, Iran

⁴ Shimi Pajohan Sabze Nikan, Tehran, Iran

⁵ Department of Civil, Chemical, Environmental, and Material Engineering (DICAM), Alma Mater Studiorum – University of Bologna, Bologna, Italy

10.22059/jchpe.2023.351673.1418

Abstract

Metoprolol has been widely used for controlling high blood pressure, preventing myocardial reinfarction, setting rate changes, setting heart rhythm, treatment of chronic angina and preventing excessive bleeding during surgery. The purpose of this research is formulation and manufacture of extended release tablets of metoprolol succinate that conform to all the in vitro physicochemical US Pharmacopoeia national formulary (USP32). For preparing the tablets, the hydrophilic HPMC(K100M) polymer was used in direct compression method. Release of metoprolol in phosphate buffer having pH=6.8 (USP32) was measured by HPLC. Also, using experimental correlation of diffusivity in buffer medium and Gurney-Lurie charts during tablet enlargement with time, diffusion coefficients of drug and partition coefficients were obtained at different time steps. The rate of drug release depends on the type, viscosity and polymer concentration. Drug release results over 20 hours for polymers of HPMC(K100M), HPMC(K4M), HPMC(K15M), polyethylene oxide, ethyl cellulose, Eudragit (RL100) were investigated and compared. The results demonstrated that HPMC(K100M) met the standards of USP32 very well and was superior over the other polymers tested.

Keywords

Metoprolol

Extended-Release Tablets

HPMC Polymer

Mass Transfer

Mehta M, Keerthy HS, Yadav RP. Sustained Release Matrix Tablet: An Overview. Asian Journal of Pharmaceutical Research and Development. 2021 Jun 15;9(3):112-7. https://doi.org/https://doi.org/10.22270/ajprd.v9i3.954
Ratnaparkhi MP, Gupta Jyoti P. Sustained release oral drug delivery system-an overview. Terminology. 2013;3(4):10-22270.
Adepu, Shivakalyani, and Seeram Ramakrishna. "Controlled drug delivery systems: current status and future directions." Molecules 26.19 (2021): 5905. https://doi.org/10.3390/molecules26195905
Pharmacopeia US. USP 32, General Chapters, Validation of Compendial Methods. Rockville, Maryland: United States Pharmacopoeial Convention, Inc.
Odidi A, Odidi I, inventors; 3489469 CANADA Inc, ITELLIPHARMACEUTICS CORP, IntelliPharmaCeutics Corp, assignee. Extended release pharmaceuticals. United States patent US 7,858,119. 2010 Dec 28.
Aquilante CL, Terra SG, Schofield RS, Pauly DF, Hatton PS, Binkley PF, Johnson JA. Sustained restoration of autonomic balance with long-but not short-acting metoprolol in patients with heart failure. Journal of cardiac failure. 2006 Apr 1;12(3):171-6. https://doi.org/10.1016/j.cardfail.2005.12.002
Gohel MC, Parikh RK, Nagori SA, Jena DG. Fabrication of modified release tablet formulation of metoprolol succinate using hydroxypropyl methylcellulose and xanthan gum. Aaps pharmscitech. 2009 Mar;10(1):62-8. DOI: 10.1208/s12249-008-9174-1
Sun X, Wu L, Maharjan A, Sun H, Hu X, York P, Sun H, Zhang J, Yin X. Static and dynamic structural features of single pellets determine the release behaviors of metoprolol succinate sustained-release tablets. European Journal of Pharmaceutical Sciences. 2020 Jun 15;149:105324. https://doi.org/10.1016/j.ejps.2020.105324
Salve PM, Surawase RK. Formulation Development and In-vitro Evaluation of Sustained Release Tablets of Metoprolol Succinate. http://dx.doi.org/10.52711/0975-4377.2021.00044
Sharma GN, Bhurat MR, Shastry VM, Shrivastava B. Formulation and Development of Metoprolol Succinate Sustained Release Matrix tablet using Remusatia vivipara tubers mucilage. Research Journal of Pharmacy and Technology 2021 10;14(10):5405-5410. https://doi.org/10.52711/0974-360X.2021.00942
Kumar AR, Aeila AS. Sustained release matrix type drug delivery system: An overview. World J Pharma pharm Sci. 2019 Oct 24;8(12):470-80. http://dx.doi.org/10.20959/wjpps20201-15241
Kendall MJ, Maxwell SR, Sandberg A, Westergren G. Controlled release metoprolol. Clinical pharmacokinetics. 1991 Nov;21(5):319-30. https://doi.org/10.2165/00003088-199121050-00001
Calabrese RV, Kresta SM, Liu MY. Recognizing the 21 most influential contributions to mixing research. Chemical Engineering Progress. 2014;110(1):20-9.
Gurney HP, Lurie J. Charts for Estimating Temperature Distributions in Heating or Cooling Solid Shapes. Industrial & Engineering Chemistry. 1923 Nov 1;15(11):1170-2. https://doi.org/10.1021/ie50167a028