(260e) Advanced Control Strategies for a Continuous Tableting Line Via Hot Melt Extrusion

Authors: 
Rehrl, J., European Consortium for Continuous Pharmaceutical Manufacturing (ECCPM)
Sacher, S., Research Center Pharmaceutical Engineering
Celikovic, S., Institute of Automation and Control, Graz University of Technology
Poms, J., Research Center Pharmaceutical Engineering GmbH
Kirchengast, M., Institute of Automation and Control, Graz University of Technology
Kruisz, J., Research Center Pharmaceutical Engineering GmbH
Sipek, M., evon GmbH
Salar-Behzadi, S., Research Center Pharmaceutical Engineering GmbH
Berger, H., Merck KG & Co Werk Spittal
Stark, G., Merck KG & Co Werk Spittal
Horn, M., Graz University of Technology
Khinast, J. G., Research Center Pharmaceutical Engineering
From a processing point-of-view the shift to continuous manufacturing mode in pharmaceutical industry is supported by the fact that most common unit operations are continuous machinery by design, such as feeding, tableting or granulation. In-line monitoring tools to supply real-time process data and to trigger control actions are available. One remaining challenge is the establishment of real-time control concepts that enable a fully automated, yet still flexible process, capable to cope with raw material variability and process events.

In this study a feedback control strategy for a continuous tablet manufacturing line has been developed. The line consists of a hot melt extrusion and pelletizing system to produce pellets of API and polymer. The pellets are transported to a direct compaction line, blended with a pre-mix of excipients and compacted to tablets. A PAT strategy to monitor critical quality attributes of intermediates and product was implemented. Different control loops covering quality and mass flow rate were designed. PID controllers were applied for API concentration in the melt and the blend, strand temperature and strand diameter corresponding to pellet thickness. Model predictive control was used to coordinate the mass flow rates of the different unit operations. The presentation highlights an assessment of different control concepts for the line, in which the tablet press, the extruder or none act as master unit.