TY - JOUR
T1 - Towards a novel continuous HME-Tableting line: Process development and control concept
AU - Sacher, Stephan
AU - Celikovic, Selma
AU - Rehrl, Jakob
AU - Poms, Johannes
AU - Kirchengast, Martin
AU - Kruisz, Julia
AU - Sipek, Martin
AU - Salar-Behzadi, Sharareh
AU - Berger, Hannes
AU - Stark, Gerald
AU - Horn, Martin
AU - Khinast, Johannes G.
PY - 2020/1/15
Y1 - 2020/1/15
N2 - 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.
AB - 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.
KW - Continuous manufacturing
KW - Advanced process control
KW - Model predictive control
KW - Hot melt extrusion
KW - Direct compaction
KW - Pat strategy
KW - Control concept
UR - http://www.scopus.com/inward/record.url?scp=85074603905&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2019.105097
DO - 10.1016/j.ejps.2019.105097
M3 - Article
SN - 0928-0987
VL - 142
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
M1 - 105097
ER -