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

This study aimed to develop and optimize a manufacturing process for bilayer film-coated tablets containing extendedrelease 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