Improving Pellet Quality in a Pharmaceutical Hot Melt Extrusion Process via PID Control and LOLIMOT-Based MPC
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ORIGINAL ARTICLE
Improving Pellet Quality in a Pharmaceutical Hot Melt Extrusion Process via PID Control and LOLIMOT-Based MPC Jakob Rehrl 1 Martin Horn 2
&
Martin Kirchengast 2 & Selma Celikovic 2 & Stephan Sacher 1 & Julia Kruisz 1 & Johannes Khinast 1,3 &
# The Author(s) 2019
Abstract Purpose The aim of this paper is the development of a process control concept for a hot melt extrusion (HME) and pelletization process. The new concept should improve the particle size distribution of the pellets produced. Methods Production of pellets containing an active pharmaceutical ingredient (API) can be achieved by means of HME, followed by a pelletization process step. The quality of pellets produced depends on the strand temperature at the pelletizer’s inlet and the pelletizer’s intake speed. This paper presents a strategy for the strand diameter and temperature control based on adjusting the cooling intensity on the cooling track between the HME and the pelletization step and altering the pelletizer’s intake speed. Two concepts are presented and compared to the open-loop operation of the system: the first one is model predictive control (MPC) in combination with a model based on the local linear model tree (LOLIMOT) algorithm, and the second one is PID control. The quality of the pellets produced was analyzed in terms of particle size distribution (PSD). Results By implementation of the two control concepts, strand temperature and diameter could be kept close to the desired set points. Consequently, the presented concepts yielded pellets with a narrower particle size distribution than the open-loop operation of the plant. Conclusions The application of the presented control strategies can improve the quality of the pellets produced by an HME and pelletization system in terms of their particle size distribution. Keywords Continuous manufacturing . Hot melt extrusion . Model predictive control . Local linear model tree . Process modeling
Introduction This paper presents a model-based control system for the strand temperature and strand diameter in a pharmaceutical hot melt extrusion (HME) process. HME processes are used in pharmaceutical manufacturing to produce advanced dosage forms, e.g., amorphous solid dispersions (ASDs) for improving solubility [1] and for producing oral dosage forms containing poorly soluble active pharmaceutical ingredients (APIs) [2] or for sustained-release
* Jakob Rehrl [email protected] 1
Research Center Pharmaceutical Engineering, Graz, Austria
2
Institute of Automation and Control, Graz University of Technology, Graz, Austria
3
Institute of Process and Particle Engineering, Graz University of Technology, Graz, Austria
tablets [3] and pellets [4]. HME processes do not require solvents and are reliable and reproducible [5]. After the extrusion step, the extruded strands can be cut into pellets of desired size, which can be filled into capsules or blended with excipients and pressed into tablets. There are several methods of producing pellets from the extrudates [6]. In this study,
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