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Advanced Model Predictive Feedforward/Feedback Control of a Tablet Press

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Abstract

In continuous pharmaceutical manufacturing, real-time precise control of critical quality attributes (CQAs) is necessary for quality by design (QbD)-based manufacturing and real-time release (RTR) with minimum consumption of time, space, and resources. Pharmaceutical tablets can be produced through different routes with a common tablet press unit operation always placed at the end of the manufacturing process. Therefore, the tablet press is a crucial unit operation directly influencing the CQAs irrespective of manufacturing routes. Despite this, little attention has been paid to the development of an advanced efficient control system for the tablet press. Process modeling can be used as an efficient virtual experimentation tool to design, compare, and evaluate different control systems. We developed a model in Simulink (Mathworks) that includes two master control loops for tablet weight and hardness and a slave feedback loop controlling the compaction force applied to each tablet. We examined the performance of different control strategies based on proportional integral derivative (PID) control and model predictive control (MPC), as well as feedforward/feedback control. We found that a hybrid MPC-PID control strategy outperforms the PID-only control strategy. We also observed that the addition of a feedforward controller further improves the performance of the hybrid MPC-PID control strategy.

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Abbreviations

Symbols:

Variables units

H:

Height (m)

m:

Mass (kg)

MCF:

Main compression force (kN)

RMSE:

Root mean square error (kp, g, kN)

ISE:

Integral of square error (kp2 s, g2 s, kN2 s)

IAE:

Integral of absolute error (kp s, g s, kN s)

ITAE:

Integral of time absolute error (kp s2, g s2, kN s2)

T2P:

Time to product (s)

M2P:

Magnitude to product (kp, g, kN)

D2R:

Disturbance to reject (s)

P:

Proportional constant (mm/kN, kN/g)

I:

Integral constant (s)

D:

Derivative constant (s)

API:

Active pharmaceutical ingredient

CQAs:

Critical quality attributes

LTI:

Linear time invariant

OE:

Output error

PAT:

Process analytical technology

PID:

Proportional integral derivative

QbD:

Quality by design

MPC:

Model predictive control

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Acknowledgements

This work is supported by the National Science Foundation Engineering Research Center on Structured Organic Particulate Systems, through grant NSF-ECC 0540855, Rutgers Research Council, through grant 202342 RC-17 to Singh R, and by the US Food and Drug Administration (FDA), through grant 11695471.

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Authors and Affiliations

  1. Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA

    Nicholas Townsend Haas, Marianthi Ierapetritou & Ravendra Singh

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  1. Nicholas Townsend Haas
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  2. Marianthi Ierapetritou
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  3. Ravendra Singh
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Correspondence to Ravendra Singh.

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Haas, N.T., Ierapetritou, M. & Singh, R. Advanced Model Predictive Feedforward/Feedback Control of a Tablet Press. J Pharm Innov 12, 110–123 (2017). https://doi.org/10.1007/s12247-017-9276-y

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  • DOI: https://doi.org/10.1007/s12247-017-9276-y

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