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

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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
Publication statusE-pub ahead of print - 2019

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