Improving Pellet Quality in a Pharmaceutical Hot Melt Extrusion Process via PID Control and LOLIMOT-Based MPC

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Abstract

Purpose:The aim of this paper is the development of a process control concept for a hot melt extrusion (HME) and pelletizationprocess. The new concept should improve the particle size distribution of the pellets roduced.
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’sinlet and the pelletizer’s intake speed. This paper presents a strategy for the strand diameter and temperature control based onadjusting the cooling intensity on the cooling track between the HME and the pelletization step and altering the pelletizer’sintakespeed. Two concepts are presented and compared to the open-loop operation of the system: the first one is model predictivecontrol (MPC) in combination with a model based on the local linear model tree (LOLIMOT) algorithm, and the second one isPID 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 setpoints. Consequently, the presented concepts yielded pellets with a narrower particle size distribution than the open-loopoperation of the plant.ConclusionsThe application of the presented control strategies can improve the quality of the pellets produced by an HME andpelletization system in terms of their particle size distribution.
Original languageEnglish
Number of pages12
JournalJournal of pharmaceutical innovation
DOIs
Publication statusE-pub ahead of print - 2019

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Particle Size
Linear Models
Pharmaceutical Preparations
Temperature

Cite this

@article{bc4d36a3fb0249358bcd1a2cc38ca86b,
title = "Improving Pellet Quality in a Pharmaceutical Hot Melt Extrusion Process via PID Control and LOLIMOT-Based MPC",
abstract = "Purpose:The aim of this paper is the development of a process control concept for a hot melt extrusion (HME) and pelletizationprocess. The new concept should improve the particle size distribution of the pellets roduced.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’sinlet and the pelletizer’s intake speed. This paper presents a strategy for the strand diameter and temperature control based onadjusting the cooling intensity on the cooling track between the HME and the pelletization step and altering the pelletizer’sintakespeed. Two concepts are presented and compared to the open-loop operation of the system: the first one is model predictivecontrol (MPC) in combination with a model based on the local linear model tree (LOLIMOT) algorithm, and the second one isPID 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 setpoints. Consequently, the presented concepts yielded pellets with a narrower particle size distribution than the open-loopoperation of the plant.ConclusionsThe application of the presented control strategies can improve the quality of the pellets produced by an HME andpelletization system in terms of their particle size distribution.",
author = "Jakob Rehrl and Martin Kirchengast and Selma Celikovic and Stephan Sacher and Julia Kruisz and Johannes Khinast and Martin Horn",
year = "2019",
doi = "10.1007/s12247-019-09417-0",
language = "English",
journal = "Journal of pharmaceutical innovation",
issn = "1939-8042",
publisher = "Springer New York",

}

TY - JOUR

T1 - Improving Pellet Quality in a Pharmaceutical Hot Melt Extrusion Process via PID Control and LOLIMOT-Based MPC

AU - Rehrl, Jakob

AU - Kirchengast, Martin

AU - Celikovic, Selma

AU - Sacher, Stephan

AU - Kruisz, Julia

AU - Khinast, Johannes

AU - Horn, Martin

PY - 2019

Y1 - 2019

N2 - Purpose:The aim of this paper is the development of a process control concept for a hot melt extrusion (HME) and pelletizationprocess. The new concept should improve the particle size distribution of the pellets roduced.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’sinlet and the pelletizer’s intake speed. This paper presents a strategy for the strand diameter and temperature control based onadjusting the cooling intensity on the cooling track between the HME and the pelletization step and altering the pelletizer’sintakespeed. Two concepts are presented and compared to the open-loop operation of the system: the first one is model predictivecontrol (MPC) in combination with a model based on the local linear model tree (LOLIMOT) algorithm, and the second one isPID 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 setpoints. Consequently, the presented concepts yielded pellets with a narrower particle size distribution than the open-loopoperation of the plant.ConclusionsThe application of the presented control strategies can improve the quality of the pellets produced by an HME andpelletization system in terms of their particle size distribution.

AB - Purpose:The aim of this paper is the development of a process control concept for a hot melt extrusion (HME) and pelletizationprocess. The new concept should improve the particle size distribution of the pellets roduced.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’sinlet and the pelletizer’s intake speed. This paper presents a strategy for the strand diameter and temperature control based onadjusting the cooling intensity on the cooling track between the HME and the pelletization step and altering the pelletizer’sintakespeed. Two concepts are presented and compared to the open-loop operation of the system: the first one is model predictivecontrol (MPC) in combination with a model based on the local linear model tree (LOLIMOT) algorithm, and the second one isPID 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 setpoints. Consequently, the presented concepts yielded pellets with a narrower particle size distribution than the open-loopoperation of the plant.ConclusionsThe application of the presented control strategies can improve the quality of the pellets produced by an HME andpelletization system in terms of their particle size distribution.

U2 - 10.1007/s12247-019-09417-0

DO - 10.1007/s12247-019-09417-0

M3 - Article

JO - Journal of pharmaceutical innovation

JF - Journal of pharmaceutical innovation

SN - 1939-8042

ER -