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.