Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation

Niels Nicolaï; Fien De Leersnyder; Dana Copot; Michiel Stock; Clara M. Ionescu; Krist V. Gernaey; Ingmar Nopens; Thomas De Beer

doi:10.1002/aic.16161

Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation

Niels Nicolaï, Fien De Leersnyder, Dana Copot, Michiel Stock, Clara M. Ionescu, Krist V. Gernaey, Ingmar Nopens, Thomas De Beer^*

^*Corresponding author for this work

Ghent University

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Assuring compliance of intermediate and final quality attributes in a continuous pharmaceutical manufacturing campaign is of utmost importance. Application of corrective actions might be required in real‐time. This work exemplifies the steps needed to identify a linear pulse transfer function for the dynamic behavior of the granule liquid‐to‐solid ratio (w) at the end of the granulation unit of a commercial ConsiGma^TM‐25 production line. Near‐infrared spectroscopy was used to monitor the granule composition in‐line. The outcome for both the tracking and regulator problem using either conventional or model predictive control was implemented and evaluated. Dynamic setpoints were correctly followed and an RMSE of 0.25w with respect to the setpoint was obtained when inducing artificial disturbances. Important practical challenges were also tackled. Examples are fouling, computational limitations, and the limited flexibility of the automation software. Applying the proposed advanced process control solution offers an answer to upstream material flow rate deviations.

Original language	English
Journal	AIChE Journal
Volume	64
Issue number	7
Pages (from-to)	2500-2514
ISSN	0001-1541
DOIs	https://doi.org/10.1002/aic.16161
Publication status	Published - 2018

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title = "Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation",

abstract = "Assuring compliance of intermediate and final quality attributes in a continuous pharmaceutical manufacturing campaign is of utmost importance. Application of corrective actions might be required in real‐time. This work exemplifies the steps needed to identify a linear pulse transfer function for the dynamic behavior of the granule liquid‐to‐solid ratio (w) at the end of the granulation unit of a commercial ConsiGmaTM‐25 production line. Near‐infrared spectroscopy was used to monitor the granule composition in‐line. The outcome for both the tracking and regulator problem using either conventional or model predictive control was implemented and evaluated. Dynamic setpoints were correctly followed and an RMSE of 0.25w with respect to the setpoint was obtained when inducing artificial disturbances. Important practical challenges were also tackled. Examples are fouling, computational limitations, and the limited flexibility of the automation software. Applying the proposed advanced process control solution offers an answer to upstream material flow rate deviations. ",

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AU - Nicolaï, Niels

AU - Leersnyder, Fien De

AU - Copot, Dana

AU - Stock, Michiel

AU - Ionescu, Clara M.

AU - Gernaey, Krist V.

AU - Nopens, Ingmar

AU - Beer, Thomas De

PY - 2018

Y1 - 2018

N2 - Assuring compliance of intermediate and final quality attributes in a continuous pharmaceutical manufacturing campaign is of utmost importance. Application of corrective actions might be required in real‐time. This work exemplifies the steps needed to identify a linear pulse transfer function for the dynamic behavior of the granule liquid‐to‐solid ratio (w) at the end of the granulation unit of a commercial ConsiGmaTM‐25 production line. Near‐infrared spectroscopy was used to monitor the granule composition in‐line. The outcome for both the tracking and regulator problem using either conventional or model predictive control was implemented and evaluated. Dynamic setpoints were correctly followed and an RMSE of 0.25w with respect to the setpoint was obtained when inducing artificial disturbances. Important practical challenges were also tackled. Examples are fouling, computational limitations, and the limited flexibility of the automation software. Applying the proposed advanced process control solution offers an answer to upstream material flow rate deviations.

AB - Assuring compliance of intermediate and final quality attributes in a continuous pharmaceutical manufacturing campaign is of utmost importance. Application of corrective actions might be required in real‐time. This work exemplifies the steps needed to identify a linear pulse transfer function for the dynamic behavior of the granule liquid‐to‐solid ratio (w) at the end of the granulation unit of a commercial ConsiGmaTM‐25 production line. Near‐infrared spectroscopy was used to monitor the granule composition in‐line. The outcome for both the tracking and regulator problem using either conventional or model predictive control was implemented and evaluated. Dynamic setpoints were correctly followed and an RMSE of 0.25w with respect to the setpoint was obtained when inducing artificial disturbances. Important practical challenges were also tackled. Examples are fouling, computational limitations, and the limited flexibility of the automation software. Applying the proposed advanced process control solution offers an answer to upstream material flow rate deviations.

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DO - 10.1002/aic.16161

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Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation

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