Process Modeling in the Pharmaceutical Industry using the Discrete Element Method

Ketterhagen, William R.; Ende, Mary T. am; Hancock, Bruno C.

doi:10.1002/jps.21466

Cited by 209 publications

(145 citation statements)

References 293 publications

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“…There has been a considerable interest in mechanistic models for pharmaceutical processes during recent years [see, e.g., the reviews by Kremer and Hancock (2006) and Ketterhagen et al (2009)]. Since the active pharmaceutical ingredient and various excipient materials typically are handled and processed in powdered form during pharmaceutical development and manufacturing, it is evident that powder technology underlies many important unit operations, especially for the generally preferred solid oral dosage forms (tablets and tablet-like delivery vehicles).…”

Section: Introductionmentioning

confidence: 99%

Compression mechanics of granule beds: A combined finite/discrete element study

Frenning

2010

Chemical Engineering Science

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Compression of three-dimensional beds comprising of 1000 plastically deforming initially spherical granules is investigated by using the combined finite/discrete element (FE/DE) method. The material model is formulated within the framework of multiplicative plasticity, and utilizes a density-dependent elliptic yield surface that allows porous particles to both deform and to densify plastically, whereas only volume-preserving plastic deformation is possible for nonporous ones. Granules with different characteristics (yield stress and initial porosity) are studied, and the relationship between the single-granule properties and the global compression behaviour of the granule bed is investigated. It is demonstrated that the FE/DE method may shed light on the deformation and densification behaviour of individual granules, since the size and shape of each granule are continually determined as an integral part of the solution procedure, and that the method thus provides a comprehensive picture of the processes occurring during confined compression of granular materials.

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Section: Introductionmentioning

confidence: 99%

Compression mechanics of granule beds: A combined finite/discrete element study

Frenning

2010

Chemical Engineering Science

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“…Approximation of shape using this technique produces undesired surface roughness for the modelled particles [16]. However, the induced roughness can be controlled by increasing the number of spheres, though this has a negative impact on the computational efficiency.…”

Section: Introductionmentioning

confidence: 99%

Effect of particle shape on flow in discrete element method simulation of a rotary batch seed coater

et al. 2016

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In the seed processing industry, rotary batch seed coaters are widely used for providing a protective coating layer (consisting of various ingredients including fertilisers and crop protection chemicals) on the seeds. Seed motion and mixing are important in ensuring uniform coating. In the batch seed coater, the base of a cylindrical vessel rotates, whilst the cylindrical wall is stationary and two baffles turn the bed over for mixing. In the present study, the Discrete Element Method (DEM) is used to simulate the effect of particle shape on motion and mixing in this device. Corn seed is used as a model material and the effect of its shape on motion is analysed by considering two approaches: (1) manipulation of rolling friction to account for shape as it is commonly used in the field; (2) approximation of the actual shape by a number of overlapping spheres of various sizes. The geometry of corn seeds is captured using X-Ray micro tomography and then the ASG2013 software (Cogency, South Africa) is used to generate and optimise the arrangement of the overlapping spheres. A comparison is made of the predicted tangential and radial velocity distributions of the particles from DEM and those measured experimentally. It is concluded that for rapid shearing systems with short collisional contacts a small number of clumped spheres suffices to provide a reasonable agreement with experimental results. Equally well, manipulating the rolling friction coefficient can provide results that match experiments but its most suitable value is unknown a priori, hence the approach is empirical rather than predictive. 2

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“…Frictional forces dominate for granular materials as cohesive forces may be considered negligible due to the large impact of gravity. The importance of the interparticle friction forces during flow may be characterised by numerical modeling which is an important and powerful tool utilised in the pharmaceutical area (Ketterhagen et al, 2009). The discrete element method (DEM) (Cundall and Strack, 1979) has been used extensively to investigate flowability of powders and granular materials (Aarons and Sundaresan, 2006;Bierwisch et al, 2009;Datta et al, 2008;Zhou et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The influence of rolling friction on the shear behaviour of non-cohesive pharmaceutical granules – An experimental and numerical investigation

Persson

Frenning

2013

European Journal of Pharmaceutical Sciences

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Granule shear behaviour was investigated experimentally and numerically to evaluate the reliability of the numerical model. Additionally, parameters affecting the ensuing flow regimeselastic quasi-static and inertial non-collisional -were highlighted. Furthermore, the influence of using the Lees-Edwards periodic boundary conditions or the standard boundary conditions was studied. Experiments were performed with microcrystalline cellulose granules of three size distributions using the FT4 powder rheometer. The numerical parameters, particle size, effective density, and particle stiffness were selected to match the experimental conditions. Experimentally, an unexpected particle size effect was evident where the resistance to shear increased with particle size. Numerically, combining rolling friction and increased shear rate enabled a transition from the inertial non-collisional to the elastic quasi-static regime at a reduced sliding friction coefficient. Presumably, this is an effect of increased particle overlap creating stronger contacts and facilitating force chain formation. Both boundary conditions provided comparable results provided a correction of system size was made, where larger systems were required for the standard boundary conditions. A satisfactory qualitative agreement between the experimentally and numerically determined yield loci emphasised the predictive capacity of the DEM. Rolling friction was in addition concluded to be an essential model parameter for obtaining an improved quantitative agreement.2

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Process Modeling in the Pharmaceutical Industry using the Discrete Element Method

Cited by 209 publications

References 293 publications

Compression mechanics of granule beds: A combined finite/discrete element study

Compression mechanics of granule beds: A combined finite/discrete element study

Effect of particle shape on flow in discrete element method simulation of a rotary batch seed coater

The influence of rolling friction on the shear behaviour of non-cohesive pharmaceutical granules – An experimental and numerical investigation

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