International Journal of Drug Delivery Technology
Volume 14, Issue 2

Formulation Optimization and Preparation of Amlodipine and Telmisartan Double-layer Tablets (5/40 Mg) using Wet Granulation Method

Duyen Thi My Huynh1, Huynh Thien Hai1, Tran Huu Loc1, Minh-Ngoc T Le1, Phuoc-Vinh Nguyen2*

1Can Tho University of Medicine and Pharmacy

2School of Medicine, Vietnam National University Ho Chi Minh City

Received: 09th May, 2024; Revised: 25th May, 2024; Accepted: 05th June, 2024; Available Online: 25th June, 2024

ABSTRACT

The two-layer tablet of amlodipine and telmisartan is an effective strategy to manage hypertension disease through a combination of various treatment mechanisms. However, the spray-drying method is currently used to prepare telmisartan tablets due to its extremely low solubility, which requires sophisticated equipment. In this study, wet granulation was applied to fabricate this two-layer tablet. Furthermore, design of experiments were deployed to design and optimize the formulation in order to obtain an in-vitro equivalence with the reference drug. As a result, a formulation of the two-layer table using the wet granulation method was successfully developed and optimized. The obtained tablet showed an in-vitro equivalence with the reference drug (with f2 superior to 50 for both amlodipine and telmisartan). Furthermore, the obtained tablet also met a set of in-house standards, including appearance, identification, assay, and dissolution rate. This study provided not a novel but effective and simple method of fabrication for amlodipine-telmisartan tablets using wet granulation. Furthermore, the obtained results also highlighted the significant contribution of a well-established design of experiments in the development of a complex tablet formulation.

Keywords: Amlodipine, Telmisartan, Two-layer tablets, In-vitro equivalence, Wet granulation, Design experiment. International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.2.32

How to cite this article: Huynh DTM, Hai HT, Loc TH, Le MT, Nguyen P. Formulation Optimization and Preparation of Amlodipine and Telmisartan Double-layer Tablets (5/40 Mg) using Wet Granulation Method. International Journal of Drug Delivery Technology. 2024;14(2):810-826.

REFERENCES

  1. Kasture A, Ramteke M. Simultaneous UV-spectrophotometric method for the estimation of atenolol and amlodipine besylate in combined dosage Indian J Pharm Sci. 2006;68(3). Available from: doi: 10.4103/0250-474X.26665
  2. Organization WH. Guideline for the pharmacological treatment of hypertension in adults. World Health Organization; 2021.
  3. Elliott WJ, Ram CVS. Calcium channel blockers. J Clin 2011;13(9):687. Available from: doi: 10.1111/j.1751- 7176.2011.00513.x. Epub 2011 Jul 27.
  4. Taylor AA, Siragy H, Nesbitt Angiotensin Receptor Blockers: Pharmacology, Efficacy, and Safety: Angiotensin Receptor Blockers. J Clin Hypertens. 2011;13(9):677–86. Available from: doi: 10.1111/j.1751-7176.2011.00518.x. Epub 2011 Jul 27.
  5. Ministry of Health of Vietnam. Vietnamese National Drug Formulary. 2018.
  6. Xie M, Tang T, Liang Efficacy of single‐pill combination in uncontrolled essential hypertension: A systematic review and network meta‐analysis. Clin Cardiol. 2023;46(8):886–98. Available from: doi: 10.1002/clc.24082.
  7. The Patent Cooperation Treaty. Bilayer tablet comprising Telmisartan and Amlodipine. 2006.
  8. ICH Harmonised Guideline. Q2(R1). Validation of Analytical procedures text and methodology. 2022.
  9. Kottai MA, Sankhla R, Gupta S, Smith AA, Manavalan R. Development and validation of a reversed phase HPLC method for simultaneous determination of amlodipine and telmisartan in pharmaceutical dosage J. Appl. Chem. Res. 2010;12:43-
  10. Maimoon S, Reddy KNK, Swetha P. RP-HPLC method development and validation for simultaneous estimation of Amlodipine besylate and Telmisartan in tablet dosage form. Indian J Res Pharm Biotechnol. 2017;5(1):74-76.
  11. Patra BR, Mohan S, Gowda N. International conference on harmonization recommended forced degradation studies and development of a new validated isocratic reverse-phase ultra high-performance liquid chromatography method for the simultaneous estimation of telmisartan and amlodipine in bulk drug and marketed formulation. Asian J Pharm Clin Res. 2019;12(6):250–258. Available from: doi: 22159/ajpcr.2019. v12i6.32629.
  12. Kayillo S, Dennis GR, Shalliker RA. Retention of polycyclic aromatic hydrocarbons on propyl-phenyl stationary phases in reversed-phase high performance liquid chromatography. J Chromatogr 2007;1148(2):168–76. Available from: https://doi. org/10.1016/j.chroma.2007.03.004.
  13. Kotamarthy L, Dan A, Karkala S, Parvani S, Román-Ospino AD, Ramachandran R. Twin-screw granulation: Mechanistic understanding of the effect of material properties on key granule quality attributes through the analysis of mixing dynamics and granulation rate mechanisms. Adv Powder Technol. 2023;34(9):104137. Available from: https://doi.org/10.1016/j. 2023.104137.
  14. Van der Merwe J, Steenekamp J, Steyn D, Hamman The role of functional excipients in solid oral dosage forms to overcome poor drug dissolution and bioavailability. Pharmaceutics. 2020;12(5):393. Available from: doi: 10.3390/ pharmaceutics12050393.
  15. Huynh DTM, Tran VH, Le MNT, Huynh VH, Pham Floating tablets incorporating curcumin solid dispersion as a potential pharmaceutical dosage form for stomach cancer treatment. J Appl Pharm Sci. 2023;13(4):240–50. Available from: doi: 10.7324/JAPS.2023.114417.
  16. Huynh DTM, Hai HT, Hau NM, Lan HK, Vinh TP, De Tran V, et Preparations and characterizations of effervescent granules containing azithromycin solid dispersion for children and elder: Solubility enhancement, taste-masking, and digestive acidic protection. Heliyon. 2023;9(6): e16592. Available from: doi: 10.1016/j.heliyon.2023.e16592.