Hybrid models to support development of fluid bed granulation processes

The hybrid modeling strategy which is based on the integration of mechanistic and data-driven models is proposed and applied on fluidized bed granulation processes. The tight combination of empirical process knowledge by means of a mechanistic model and the multivariate data from PAT sensors allowed to gain benefits from both components. The hybrid strategy avoids any discrepancies between model and real process, increases transferability and general applicability of the model, as well as allows a smooth integration of Quality-by-Design principles for oral solid dosage forms. In this contribution, two illustrative application examples for fluidized bed spray agglomeration and fluidized bed layering or coating processes are presented. It was shown that the proposed strategy can be successfully applied to support process development on different scales. It results in better process understanding, creation of regime maps and might end with the generation of a digital twin.