Powder flow and mixing in different tablet press feed frames

Siegmann, Eva; Forgber, Thomas; Toson, Peter; Martinetz, Michael C.; Kureck, Hermann; Brinz, Thomas; Manz, Stefan; Grass, Torsten; Khinast, Johannes G.

doi:10.1016/j.apt.2019.11.031

Cited by 25 publications

(3 citation statements)

References 36 publications

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“…The discrete element modeling approaches are rather used to describe specific sub-processes such as the compression [ 22 , 23 , 24 , 25 ] or the die filling [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. The particles in a typical DEM approach are modeled rigidly and are mainly used for explanatory models of physical behavior rather than for engineering purposes, which is to some extend the approach of the Finite Element Method (FEM), allowing the consideration of stresses within the machine design [ 22 , 33 , 34 ].…”

Section: Tableting and Its Simulationmentioning

confidence: 99%

Process Modeling and Simulation of Tableting—An Agent-Based Simulation Methodology for Direct Compression

et al. 2021

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In pharmaceutical manufacturing, the utmost aim is reliably producing high quality products. Simulation approaches allow virtual experiments of processes in the planning phase and the implementation of digital twins in operation. The industrial processing of active pharmaceutical ingredients (APIs) into tablets requires the combination of discrete and continuous sub-processes with complex interdependencies regarding the material structures and characteristics. The API and excipients are mixed, granulated if required, and subsequently tableted. Thereby, the structure as well as the properties of the intermediate and final product are influenced by the raw materials, the parametrized processes and environmental conditions, which are subject to certain fluctuations. In this study, for the first time, an agent-based simulation model is presented, which enables the prediction, tracking, and tracing of resulting structures and properties of the intermediates of an industrial tableting process. Therefore, the methodology for the identification and development of product and process agents in an agent-based simulation is shown. Implemented physical models describe the impact of process parameters on material structures. The tablet production with a pilot scale rotary press is experimentally characterized to provide calibration and validation data. Finally, the simulation results, predicting the final structures, are compared to the experimental data.

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Section: Tableting and Its Simulationmentioning

confidence: 99%

Process Modeling and Simulation of Tableting—An Agent-Based Simulation Methodology for Direct Compression

et al. 2021

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“…Over the past years, we have created a database of the most common twin-screw extruder elements of major pharma extruder manufacturers of various scales (12-mm, 16-mm, 18-mm, and 27-mm extruder sizes) (30,(83)(84)(85). Since analyzing the flow and mixing behavior in such detail is computationally expensive, we developed an in-house software for accelerated simulations running on graphic cards (GPUs): the eXtended Particle Systems (XPS) software (97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109). It is a powerful simulation platform for simulating not only complex fluids via SPH, but also complex powders via the discrete element method (DEM) with additional coupling to conventional CFD software.…”

Section: Process Development and Control Process Setup And Scale-up Vmentioning

confidence: 99%

Developing HME-Based Drug Products Using Emerging Science: a Fast-Track Roadmap from Concept to Clinical Batch

et al. 2020

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This paper presents a rational workflow for developing enabling formulations, such as amorphous solid dispersions, via hot-melt extrusion in less than a year. First, our approach to an integrated product and process development framework is described, including state-ofthe-art theoretical concepts, modeling, and experimental characterization described in the literature and developed by us. Next, lab-scale extruder setups are designed (processing conditions and screw design) based on a rational, model-based framework that takes into account the thermal load required, the mixing capabilities, and the thermo-mechanical degradation. The predicted optimal process setup can be validated quickly in the pilot plant. Lastly, a transfer of the process to any GMP-certified manufacturing site can be performed in silico for any extruder based on our validated computational framework. In summary, the proposed workflow massively reduces the risk in product and process development and shortens the drug-to-market time for enabling formulations.

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“…For gaining insights into the powder flow in a feed frame via numerical simulation, the most commonly used method is the discrete element method (DEM) [11][12][13][14][15][16][17][18]. DEM is a Lagrangian method, which is based on individually tracking each particle [19].…”

Section: Introductionmentioning

confidence: 99%

Simulation of Powder Flow Behavior in an Artificial Feed Frame Using an Euler‐Euler Model

et al. 2022

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The Eulerian approach is an alternative numerical method to the traditionally used discreet particle techniques for modeling powder flow, avoiding limitations on particle number and diameter. The feasibility of an Euler-Euler simulation in a pharmaceutical application was investigated. In two-and three-dimensional flow simulations, computational fluid dynamics models and parameters were determined and verified based on comparison with experiments. Residence time distributions were calculated to show the applicability of the Eulerian model with two granular phases under the constraint of a continuous setup. Finally, this model was implemented to improve the process understanding of the powder flow in an artificial feed frame of a rotary tablet press.

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Powder flow and mixing in different tablet press feed frames

Cited by 25 publications

References 36 publications

Process Modeling and Simulation of Tableting—An Agent-Based Simulation Methodology for Direct Compression

Process Modeling and Simulation of Tableting—An Agent-Based Simulation Methodology for Direct Compression

Developing HME-Based Drug Products Using Emerging Science: a Fast-Track Roadmap from Concept to Clinical Batch

Simulation of Powder Flow Behavior in an Artificial Feed Frame Using an Euler‐Euler Model

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