Towards a novel continuous HME-Tableting line: Process development and control concept

Stephan Sacher, Selma Celikovic, Jakob Rehrl, Johannes Poms, Martin Kirchengast, Julia Kruisz, Martin Sipek, Sharareh Salar-Behzadi, Hannes Berger, Gerald Stark, Martin Horn, Johannes G. Khinast*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The objective of this study was to develop a novel closed-loop controlled continuous tablet manufacturing line, which first uses hot melt extrusion (HME) to produce pellets based on API and a polymer matrix. Such systems can be used to make complex pharmaceutical formulations, e.g., amorphous solid dispersions of poorly soluble APIs. The pellets are then fed to a direct compaction (DC) line blended with an external phase and tableted continuously. Fully-automated processing requires advanced control strategies, e.g., for reacting to raw material variations and process events. While many tools have been proposed for in-line process monitoring and real-time data acquisition, establishing real-time automated feedback control based on in-process control strategies remains a challenge. Control loops were implemented to assess the quality attributes of intermediates and product and to coordinate the mass flow rate between the unit operations. Feedback control for the blend concentration, strand temperature and pellet thickness was accomplished via proportional integral derivative (PID) controllers. The tablet press hopper level was controlled using a model predictive controller. To control the mass flow rates in all unit operations, several concepts were developed, with the tablet press, the extruder or none assigned to be the master unit of the line, and compared via the simulation.

Original languageEnglish
Article number105097
JournalEuropean Journal of Pharmaceutical Sciences
Publication statusPublished - 15 Jan 2020


  • Continuous manufacturing
  • Advanced process control
  • Model predictive control
  • Hot melt extrusion
  • Direct compaction
  • Pat strategy
  • Control concept

ASJC Scopus subject areas

  • Pharmaceutical Science


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