International Journal of Drug Delivery Technology
Volume 15, Issue 2

Batch Scale-Up and Impact of Process Parameters on Blend Homogeneity in Production of Bilayer Film-Coated Tablets Containing Extended-Release Indapamide and Immediate-Release Amlodipine

Duyen Thi My Huynh1, Son Thanh Khuu1, Ly Ngoc Hanh1, Nguyen Duc Tuan2, Thanh Dung Phan2, Tran Van-Hoai Le3, An Viet Tran4*

1Faculty of Pharmacy, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho, Vietnam

2Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh city, Ho Chi Minh 700000, Vietnam

3Saigon Pharmaceutical Science and Technology Center, University of Medicine and Pharmacy at Ho Chi Minh City

4Faculty of Medicine, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho, Vietnam 

Received: 23rd May, 2025; Revised and Accepted: 10th Jun, 2025; Available Online: 25th Jun, 2025

ABSTRACT

This study aimed to develop and optimize a manufacturing process for bilayer film-coated tablets containing extended-release indapamide and immediate-release amlodipine besylate. The formulation process included dry mixing, final blending, bilayer compression, film coating, and quality and stability evaluations. Optimization of the dry mixing and final blending times was performed to ensure uniformity and reproducibility. For the 10,000-tablet batch, the indapamide layer was processed using a high-speed mixer for 7 minutes at 500 rpm paddle speed and 1500 rpm chopper speed, followed by 5 minutes of final blending in a cubic blender at 17 rpm. The amlodipine layer underwent both dry mixing and final blending for 5 minutes in the cubic blender. In scale-up to a 100,000-tablet batch, adjustments in mixer parameters were necessary for the indapamide layer, and an extended initial mixing time of 6 minutes was required for the amlodipine layer. The bilayer tablets were successfully compressed and film-coated, exhibiting consistent physical properties and quality attributes. Stability testing confirmed the robustness of the formulation and process. The optimized manufacturing process was found to be scalable, repeatable, and suitable for commercial production, ensuring the consistent quality of the final bilayer film-coated tablets.

Keywords: bilayer film-coated tablets, dry mixing, final blending, scale-up, stability testing

How to cite this article: Duyen Thi My Huynh, Son Thanh Khuu, Ly Ngoc Hanh, Nguyen Duc Tuan, Thanh Dung Phan, Tran Van-Hoai Le, An Viet Tran. Batch Scale-Up and Impact of Process Parameters on Blend Homogeneity in Production of Bilayer Film-Coated Tablets Containing Extended-Release Indapamide and Immediate-Release Amlodipine. International Journal of Drug Delivery Technology. 2025;15(2):397-405. doi: 10.25258/ijddt.15.2.4

Source of support: The authors would like to acknowledge the Ho Chi Minh City Department of Science and Technology, under grant number 103/QĐ-SKHCN dated February 6, 2023, and Can Tho University of Medicine and Pharmacy for supporting the study. This research was supported by the Ho Chi Minh City Department of Science and Technology.

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