Multi-dimensional population balance modeling and experimental validation of continuous powder mixing processes

Sen, Maitraye; Singh, Ravendra; Vanarase, Aditya U.; John, Joyce; Ramachandran, Rohit

doi:10.1016/j.ces.2012.06.024

Cited by 54 publications

(27 citation statements)

References 73 publications

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“…e hybrid PBM-DEM model demonstrated good qualitative agreement with experimental studies as well as full featured DEM simulations [15,18,50]. A further experimental validation of the PBM has been carried out by the authors [51] which is quantitative in nature. Figure 7 depicts the RTDs obtained from the DEM and gPROMs model.…”

Section: 24mentioning

confidence: 58%

Mathematical Development and Comparison of a Hybrid PBM-DEM Description of a Continuous Powder Mixing Process

Sen

Dubey

Singh

et al. 2013

Journal of Powder Technology

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is paper describes the development of a multidimensional population balance model (PBM) which can account for the dynamics of a continuous powder mixing/blending process. e PBM can incorporate the important design and process conditions and determine their effects on the various critical quality attributes (CQAs) accordingly. e important parameters considered in this study are blender dimensions and presence of noise in the inlet streams. e blender dynamics have been captured in terms of composition of the ingredients, (relative standard deviation) RSD, and (residence time distribution) RTD. PBM interacts with discrete element modeling (DEM) via one-way coupling which forms a basic framework for hybrid modeling. e results thus obtained have been compared against a full DEM simulation which is a more fundamental particle-level model that elucidates the dynamics of the mixing process. Results show good qualitative agreement which lends credence to the use of coupled PBM as an effective tool in control and optimization of mixing process due to its relatively fewer computational requirements compared to DEM.

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Section: 24mentioning

confidence: 58%

Mathematical Development and Comparison of a Hybrid PBM-DEM Description of a Continuous Powder Mixing Process

Sen

Dubey

Singh

et al. 2013

Journal of Powder Technology

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“…The integrated flowsheet model for direct compaction continuous tablet manufacturing process has been previously reported [6,16]. The mathematical model for powder blending, an important but complex unit operation, has been previously developed as described in [5]. The model for the tablet compression process is previously reported in Singh et al (2013) [16].…”

Section: Control Relevant Process Modelmentioning

confidence: 99%

“…In the last few years, extensive work has been done to study the continuous tablet manufacturing process [3][4][5][6]. The main focus, however, has been on powder blend uniformity, drug concentration and final end product qualities.…”

Section: Introductionmentioning

confidence: 99%

A Combined Feed-Forward/Feed-Back Control System for a QbD-Based Continuous Tablet Manufacturing Process

et al. 2015

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Abstract:Continuous pharmaceutical manufacturing together with PAT (Process Analytical Technology) provides a suitable platform for automatic control of the end product quality as desired by QbD (quality by design)-based efficient manufacturing. The precise control of the quality of the pharmaceutical product requires corrective actions in the process/raw material variability before product quality can be influenced. In this manuscript, a combined feed-forward/feed-back control system has been developed for a direct compaction continuous tablet manufacturing process. The feed-forward controller takes into account the effect of process disturbances proactively while the feed-back control system ensures the end product quality consistently. The coupled feed-forward/feed-back control system ensures the minimum variability in the final product quality irrespective of process and raw material variations. The performance of the combined control strategy has been evaluated through process simulation and is found to be more effective in comparison with a feed-back only control strategy and, therefore, demonstrates potential to further improve pharmaceutical tablet manufacturing operations.

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“…The parameter estimation can be formulated as an optimization problem with a least squares objective as outlined in Ramachandran et al [118]. Sen et al [119] have demonstrated the use of a parameterized population balance equation to model a continuous mixer. The parameters were fit by minimizing error between measured and predicted relative standard deviation (RSD) of the product composition and the API mass fraction at the mixer outlet.…”

Section: Population Balance Modelsmentioning

confidence: 99%

Modeling of Particulate Processes for the Continuous Manufacture of Solid-Based Pharmaceutical Dosage Forms

2013

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Abstract:The objective of this work is to present a review of computational tools and models for pharmaceutical processes, specifically those for the continuous manufacture of solid dosage forms. Relevant mathematical methods and simulation techniques are discussed, as is the development of process models for solids-handling unit operations. Continuous processing is of particular interest in the current study because it has the potential to improve the efficiency and robustness of pharmaceutical manufacturing processes.

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Multi-dimensional population balance modeling and experimental validation of continuous powder mixing processes

Cited by 54 publications

References 73 publications

Mathematical Development and Comparison of a Hybrid PBM-DEM Description of a Continuous Powder Mixing Process

Mathematical Development and Comparison of a Hybrid PBM-DEM Description of a Continuous Powder Mixing Process

A Combined Feed-Forward/Feed-Back Control System for a QbD-Based Continuous Tablet Manufacturing Process

Modeling of Particulate Processes for the Continuous Manufacture of Solid-Based Pharmaceutical Dosage Forms

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