Real time monitoring of powder blend bulk density for coupled feed-forward/feed-back control of a continuous direct compaction tablet manufacturing process

Singh, Ravendra; Román-Ospino, Andrés D.; Romañach, Rodolfo J.; Ierapetritou, Marianthi G.; Ramachandran, Rohit

doi:10.1016/j.ijpharm.2015.09.029

Cited by 64 publications

(27 citation statements)

References 11 publications

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“…2 Despite the increased process knowledge and measurement techniques, control of the intermediate and final quality attributes in the pharmaceutical industry is still mainly based on a fixed recipe approach, where parameters are optimized once for a theoretical steady-state output, combined with acceptance sampling strategies. 5,6 When dealing with continuous lines the flow rates of solid and liquid raw materials at the entry of the production line require tight control. In fact, changes in material throughput related to market demand can also be seen as a disturbance which needs to be compensated for to assure product quality.…”

Section: Introductionmentioning

confidence: 99%

“…The aim here is to automatically assure that critical quality attributes are consistently in agreement with the acceptance criteria in real-time. 5,6 When dealing with continuous lines the flow rates of solid and liquid raw materials at the entry of the production line require tight control. Not only is this necessary to ensure the final drug potency despite process disturbances, but also to ensure the physical characteristics of the intermediate product.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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/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 0.25%w/w 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. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2500–2514, 2018

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…Experimental work has been conducted for feeder and blender unit operations [27]. There has been some work done in the development of PAT (Process Analytical Technology) for the utilization in control strategies [28]. Based on this, work hybrid control strategies have been developed for continuous pharmaceutical manufacturing [28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

“…There has been some work done in the development of PAT (Process Analytical Technology) for the utilization in control strategies [28]. Based on this, work hybrid control strategies have been developed for continuous pharmaceutical manufacturing [28][29][30][31]. There has also been experimental work done using a commercial model predictive control platform for the continuous direct compaction process [32].…”

Section: Introductionmentioning

confidence: 99%

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

Barros¹,

Bhaskar²,

Singh³

2017

Processes

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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.

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“…With the increasing acceptance of QBD/PAT initiatives by the pharmaceutical industry, real-time analytical tools are more frequently used for improving process understanding, implementing process control, and product release. For example, NIR spectroscopy has been widely used for online/at-line analysis of solid dosage drug product in manufacturing (8)(9)(10)(11). A number of publications have shown the use of Raman for in-process monitoring and control during both drug substance and product manufacturing (8,(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

In-line ATR-UV and Raman Spectroscopy for Monitoring API Dissolution Process During Liquid-Filled Soft-Gelatin Capsule Manufacturing

Wan

Zordan

et al. 2015

AAPS PharmSciTech

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Abstract. Complete dissolution of the active pharmaceutical ingredient (API) is critical in the manufacturing of liquid-filled soft-gelatin capsules (SGC). Attenuated total reflectance UV spectroscopy (ATR-UV) and Raman spectroscopy have been investigated for in-line monitoring of API dissolution during manufacturing of an SGC product. Calibration models have been developed with both techniques for in-line determination of API potency. Performance of both techniques was evaluated and compared. The ATR-UV methodology was found to be able to monitor the dissolution process and determine the endpoint, but was sensitive to temperature variations. The Raman technique was also capable of effectively monitoring the process and was more robust to the temperature variation and process perturbations by using an excipient peak for internal correction. Different data preprocessing methodologies were explored in an attempt to improve method performance.

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Real time monitoring of powder blend bulk density for coupled feed-forward/feed-back control of a continuous direct compaction tablet manufacturing process

Cited by 64 publications

References 11 publications

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

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

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

In-line ATR-UV and Raman Spectroscopy for Monitoring API Dissolution Process During Liquid-Filled Soft-Gelatin Capsule Manufacturing

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