Author(s):
Duyen Thi My Huynh, Phuong-Thuy Tran, Tran Viet Hung, Truc-Ly Thi Duong, Van-Ha Nguyen, Dang-Khoa Nguyen
Email(s):
ndkhoa@ump.edu.vn
DOI:
10.52711/0974-360X.2026.00498 
Address:
Duyen Thi My Huynh1, Phuong-Thuy Tran1, Tran Viet Hung2, Truc-Ly Thi Duong3, Van-Ha Nguyen4, Dang-Khoa Nguyen4*
1Faculty of Pharmacy, Can Tho University of Medicine and Pharmacy, Can Tho, 900000, Vietnam.
2Institute of Drug Quality Control-Ho Chi Minh City (IDQC HCMC), Ho Chi Minh City 700000, Vietnam.
3Faculty of Traditional Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam.
4School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam.
*Corresponding Author
Published In:
Volume - 19,
Issue - 8,
Year - 2026
ABSTRACT:
Backgroud: Amlodipine and losartan potassium are widely prescribed in hypertension treatment, but their formulation poses challenges due to poor physicochemical stability. Amlodipine is hygroscopic and heat-sensitive, while losartan tends to form gels in acidic conditions, reducing dissolution. Developing a robust bilayer tablet requires overcoming these issues and ensuring reproducibility during scale-up. Methods: A dry granulation strategy was applied to minimize moisture and thermal degradation. Amlodipine layers were prepared by direct compression with different superdisintegrants, while losartan layers were optimized using crospovidone. Dissolution tests were performed at pH 1.2 and 6.8 against the reference (COZAAR XQTM, 5/100 mg). Bilayer tablets were compressed under optimized hardness conditions, coated with hydroxypropylmethylcellulose/ hydroxypropylcellulose, and evaluated for stability. Scale-up from 1,000 to 10,000 tablets employed a cubic mixer, with content uniformity assessed at different mixing times. Results: Formulation F6-AMLO (amlodipine) and F4-LOS (losartan) showed the best dissolution similarity to the reference product, with similarity factors (f2) above 50 across media. The bilayer tablets achieved strong interlayer adhesion at 30-40 N hardness for losartan and 151–180 N for whole tablets. Coating improved moisture protection without impairing drug release. Scale-up trials confirmed robust reproducibility and established optimal mixing conditions, with amlodipine achieving homogeneity after 5 minutes of blending (RSD = 0.66%), while losartan required 15 minutes of premixing followed by 5 minutes of final blending (RSD = 0.69%). Scaled-up batches met pharmacopeial specifications and showed dissolution equivalence to the reference. Conclusion: Dry granulation enabled the successful development of bilayer film-coated tablets containing amlodipine and losartan potassium. The process was robust, scalable, and reproducible, with dissolution equivalence to the reference and industrial applicability, demonstrating potential for large-scale manufacturing of stable combination antihypertensive therapy.
Cite this article:
Duyen Thi My Huynh, Phuong-Thuy Tran, Tran Viet Hung, Truc-Ly Thi Duong, Van-Ha Nguyen, Dang-Khoa Nguyen. Dry Granulation approach for Formulation Development, Scale-up and Process Optimization of Bilayer film-coated Tablets containing Amlodipine 5mg and Losartan Potassium 100mg. Research Journal of Pharmacy and Technology. 2026;19(8):3513-2. doi: 10.52711/0974-360X.2026.00498
Cite(Electronic):
Duyen Thi My Huynh, Phuong-Thuy Tran, Tran Viet Hung, Truc-Ly Thi Duong, Van-Ha Nguyen, Dang-Khoa Nguyen. Dry Granulation approach for Formulation Development, Scale-up and Process Optimization of Bilayer film-coated Tablets containing Amlodipine 5mg and Losartan Potassium 100mg. Research Journal of Pharmacy and Technology. 2026;19(8):3513-2. doi: 10.52711/0974-360X.2026.00498 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2026-19-8-15
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