Transitioning Amiodarone Tablet Manufacturing: A Comparative Study of Batch and Continuous Wet Granulation

Background/Objectives: The objective of this study was to design and optimize a continuous wet granulation process for Amiodarone hydrochloride tablets using a Design of Experiments approach. The study compared and evaluated the characteristics of granules and tablets produced via a high-shear mixer (batch process) and a twin-screw granulator (continuous process). Methods: For process optimization, a central composite design was applied to establish a design space, defining screw speed and milling size as critical process parameters (X) and dissolution rate, flowability, assay, disintegration time, and friability as dependent variables (Y). Results: Comparative results between the two processes revealed no significant differences in in-process control parameters, and all formulations successfully met the target dissolution profiles. Notably, the similarity factor (f₂) was calculated to be above 50, through which dissolution equivalence was successfully demonstrated with a high level of statistical certainty. Regarding process efficiency, lead time measurements confirmed that the continuous process dramatically reduced manufacturing time by more than 80% compared to the batch process. Conclusions: This study validates the feasibility of converting batch-based drug manufacturing to a continuous platform without altering the formulation, presenting an effective process strategy for enhancing productivity and operational efficiency in the pharmaceutical industry.