Integrating Quality by Design and Discrete Element Method Modeling for Tablet Coating Process Development

Tablet coating is affected by tablet-bed dynamics, spray exposure, and liquid application, making robust process control challenging. This study aimed to integrate the discrete element method (DEM) with Quality by Design (QbD) to support process parameter selection and development of a tablet coating control strategy. DEM simulations evaluated the effects of drum rotational speed (15, 25, and 35 rpm) and tablet-bed loading (1250, 2000, and 2750 g) on tablet residence time in a virtual spray zone. Based on the simulations, drum speed and coating suspension mass flow rate were investigated experimentally using a three-level factorial design with nine conditions and one repeated centre point. Disintegration time, tablet mass variability, mechanical strength, and visual coating defects were evaluated. DEM showed a nonlinear effect of drum speed on the variability of tablet residence time in the spray zone, with a stronger effect than bed loading. Experimental models confirmed significant effects of both process parameters on the investigated critical quality attributes (CQAs). Favourable operating regions were identified at approximately 23–30 rpm and 8–14 g/min. Conditions around 25 rpm and 11 g/min provided a favourable overall balance of the investigated quality attributes. The integration of DEM and QbD provided complementary mechanistic and experimental information for tablet coating development. The approach supported identification of a practical operating region and a representative target condition for further development of the process control strategy.