Efficient Discrete Element Method Simulation Strategy for Analyzing Large‐Scale Agitated Powder Mixers

Siegmann, Eva; Jajčević, Dalibor; Radeke, Charles; Strube, Dieter; Friedrich, Karsten; Khinast, Johannes G.

doi:10.1002/cite.201700004

Cited by 17 publications

(3 citation statements)

References 19 publications

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“…XPS is a high-performance GPU-based code and has been successfully applied to a wide range of industry-scale applications in the pharmaceutical field, e.g. tablet coating [3], batch and continuous mixing [4,5], and fluidized bed coating [6]. Implementation details are given in Refs.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Particle-level residence time data in a twin-screw feeder

Toson

Khinast

2019

Data in Brief

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A full discharge process of a twin-screw feeder has been simulated with DEM (discrete element method). The result files are available at the Mendeley Data repository (https://doi.org/10.17632/d76rzzd8r7.1) and contain the following particle data: x,y,z coordinates of the initial position inside the feeder, particle radius, and the discharge time of each particle are available at three different initial feeder fill levels. With this data it is possible to generate residence time distributions (RTDs) of arbitrary spatial regions in the feeder to analyze the material flow inside the feeder, optimize refill strategies, and ultimately improve batch definition in continuous manufacturing. Example RTDs and evaluation scripts are available in the repository.

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Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Particle-level residence time data in a twin-screw feeder

Toson

Khinast

2019

Data in Brief

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“…First, the individual screw elements that assemble the screw configuration were analyzed and parametrized using the Smoothed Particle Hydrodynamics (SPH) simulation approach. The used solver is a weekly compressible SPH solver described in more detail in ( Monaghan, 2000 , Monaghan, 1994 , Monaghan, 1992 ; Monaghan and Kajtar, 2009 ), and implemented in our in house developed particle solved XPS (eXtenden Particle System) ( Jajcevic et al, 2013 ; Kureck et al, 2019 ; Siegmann et al, 2017 ; Toson et al, 2018 ). This approach was applied before in our previous work ( Bauer et al, 2020 ; Eitzlmayr et al, 2017 , Eitzlmayr et al, 2014a ; Eitzlmayr and Khinast, 2015a , Eitzlmayr and Khinast, 2015b ; Matić et al, 2019 ) and used to characterize the dimensionless pressure and power characteristics of the investigated screw element pairs.…”

Section: Methodsmentioning

confidence: 99%

Towards predicting the product quality in hot-melt extrusion: Pilot plant scale extrusion

Matić

Alva

Eder

et al. 2021

International Journal of Pharmaceutics: X

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Following our study on the impact of hot melt extrusion (HME) process conditions on the product quality, we expanded our investigation to assessing the effect of scale-up on the product quality. To this end, we studied the influence of process settings and different scale-up variants on the active pharmaceutical ingredient (API) degradation in a pilot plant scale extruder. Six scale-up variants were investigated and none of them could replicate the product quality from the original process setup on a lab-scale extruder. By analyzing several process-dependent and -independent variables and cross referencing them to the experiments in the lab-scale extruder, we identified certain patterns. The results of the reduced order mechanistic 1D HME simulation of various process states made it possible to establish a correlation between the achieved API degradation and the local melt temperature and the exposure time in specific zones along the screw configuration. Since the same melt temperature and exposure time correlations were also valid for the lab scale-extruder, such an approach could be used in the future to predict the product quality as a function of processing conditions fully in silico prior to the first extrusion trials.

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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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Efficient Discrete Element Method Simulation Strategy for Analyzing Large‐Scale Agitated Powder Mixers

Cited by 17 publications

References 19 publications

Particle-level residence time data in a twin-screw feeder

Particle-level residence time data in a twin-screw feeder

Towards predicting the product quality in hot-melt extrusion: Pilot plant scale extrusion

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

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