A Validated Model for Design and Evaluation of Control Architectures for a Continuous Tablet Compaction Process

Fernando Nunes De Barros,Ravendra Singh,Aparajith Bhaskar

doi:10.3390/pr5040076

Fernando Nunes De Barros, Ravendra Singh + Show 1 more

Open Access

https://doi.org/10.3390/pr5040076

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Journal: Processes	Publication Date: Dec 1, 2017
Citations: 8	License type: CC BY 4.0

Affiliation: Rutgers, The State University of New Jersey

Abstract

The systematic design of an advanced and efficient control strategy for controlling critical quality attributes of the tablet compaction operation is necessary to increase the robustness of a continuous pharmaceutical manufacturing process and for real time release. A process model plays a very important role to design, evaluate and tune the control system. However, much less attention has been made to develop a validated control relevant model for tablet compaction process that can be systematically applied for design, evaluation, tuning and thereby implementation of the control system. In this work, a dynamic tablet compaction model capable of predicting linear and nonlinear process responses has been successfully developed and validated. The nonlinear model is based on a series of transfer functions and static polynomial models. The model has been applied for control system design, tuning and evaluation and thereby facilitate the control system implementation into the pilot-plant with less time and resources. The best performing control algorithm was used in the implementation and evaluation of different strategies for control of tablet weight and breaking force. A characterization of the evaluated control strategies has been presented and can serve as a guideline for the selection of the adequate control strategy for a given tablet compaction setup. A strategy based on a multiple input multiple output (MIMO) model predictive controller (MPC), developed using the simulation environment, has been implemented in a tablet press unit, verifying the relevance of the simulation tool.

Highlights

Due to the enablement of more reliable and faster drug production; the pharmaceutical industry in recent times is showing great interest in continuous manufacturing (CM) technology
The developed model was able to successfully capture the non-linear behavior of the compaction as well as tablet production rate dependent transport delays. The relevance of this model lies in its process as well as tablet production rate dependent transport delays
The applicability of the model for control system design was evaluated and the developed The applicability of the model for control system design was evaluated and the developed control strategies were implemented on an experimental setup

Summary

Introduction

Due to the enablement of more reliable and faster drug production; the pharmaceutical industry in recent times is showing great interest in continuous manufacturing (CM) technology. Integrating quality by design (QbD), quality by control (QbC), real time release (RTR) and efficient process analytical technology (PAT) can serve to cut down manufacturing costs and improve drug quality and thereby patient safety. This integration of concepts to enable the transition from batch to continuous manufacturing requires intensive research in terms of understanding processes from a mechanistic perspective rather than a black box approach. As introduced by the ICH Q8 guidance on pharmaceutical development, has required that companies demonstrate an understanding of how various elements in the process affect the product quality [1,2]. This would entail being able to correlate critical process parameters

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