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Flow and Compression of Granulated Powders: The Accuracy of Discrete Element Simulations and Assessment of Tablet Microstructure
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Simulations are powerful and important tools for gaining insight into powder processes. Ultimately, simulations have the potential to replace experiments. Thus, accurate models and insight into the essential factors for descriptions of powder behaviour are required. In this thesis, discrete element method (DEM) simulations of granule flow and compression were evaluated to deduce parameters and potential models essential for the experimental and numerical correspondence. In addition, the evolution in tablet microstructure during compression was studied using mercury porosimetry.

Granule flow was measured using angle of repose, discharge rate, and shear. The granular flow depended primarily on particle shape and surface texture due to the mutual influence of these two parameters on the inter-particle forces. Rolling friction stabilised both the heap formation and promoted shear in the elastic quasi-static flow regime. Thus, rolling friction was established to be an essential simulation parameter for the correspondence to experiments.

Current compression models often neglect the elastic compact deformation during particle loading. In this thesis, two fundamentally different models were evaluated with focus of including the elastic deformation. The first model comprised a maximal particle overlap, where elastic deformation commences. The second model accounted for the contact dependence and impingement at high relative densities. This model was based on a truncated-sphere followed by a Voronoi extension. The validity of the models was demonstrated by the elastic qualitative correspondence to experimental compressions for ductile materials.

In tablets, the void (inter-granular pore) diameter was dependent on the degree of compression. Thus, the degree of compression provides an indication of the tablet microstructure. The microstructure was subsequently observed to be related to the tablet tensile strength as inferred from a percolation threshold required for formation of coherent tablets.

In summary, this thesis has shed light onto the potential of simulating flow and compression of granulated pharmaceutical powders using DEM. Continuous work in the area are required to further improve the models to increase the experimental and numerical correspondence.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 180
Keyword [en]
Discrete Element Method, Granule, Flow, Angle of Repose, Discharge Rate, Shear, Rolling friction, Compression, Elastic deformation, Microstructure, Degree of compression, Tensile strength
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutics
Identifiers
URN: urn:nbn:se:uu:diva-208808ISBN: 978-91-554-8769-0 (print)OAI: oai:DiVA.org:uu-208808DiVA: diva2:654645
Public defence
2013-11-22, B42, BMC, Husargatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2013-10-30 Created: 2013-10-08 Last updated: 2014-01-23
List of papers
1. Flowability of surface modified pharmaceutical granules: A comparative experimental and numerical study
Open this publication in new window or tab >>Flowability of surface modified pharmaceutical granules: A comparative experimental and numerical study
2011 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 42, no 3, 199-209 p.Article in journal (Refereed) Published
Abstract [en]

Flowability - as measured by hopper discharge rate, angle of repose and Carr's index (CI) - of surface modified microcrystalline cellulose granules was investigated experimentally. Three-dimensional simulations of the granule flow were performed, using the discrete element method (DEM), including either sliding and rolling friction or sliding friction and cohesion in the model. Granule surface modification with polymer coating and lubrication was found to have a significant effect on the sliding friction coefficient. This effect was also reflected in the ensuing flow behaviour, as quantified by the experimental discharge rate and angle of repose, whereas the results for the Cl were inconclusive. The numerical results demonstrated that granular flow was qualitatively different for non-cohesive and cohesive granules, occurring in the form of individual particles for the former and in larger clusters for the latter. Rolling friction and cohesion nevertheless affected the simulated discharge rate in a similar manner, producing results comparable to those observed experimentally and calculated with the Beverloo equation. The numerical results for the cohesive granules demonstrated that cohesion alone was sufficient to produce stable heaps. However, the agreement with experimental data was satisfactory only for the non-cohesive granules, demonstrating the importance of rolling friction.

Keyword
Discharge rate, Angle of repose, Discrete element method, Rolling and sliding friction, Cohesion
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-149033 (URN)10.1016/j.ejps.2010.11.011 (DOI)000287616300004 ()21112389 (PubMedID)
Available from: 2011-03-15 Created: 2011-03-15 Last updated: 2017-12-11Bibliographically approved
2. The influence of rolling friction on the shear behaviour of non-cohesive pharmaceutical granules: An experimental and numerical investigation
Open this publication in new window or tab >>The influence of rolling friction on the shear behaviour of non-cohesive pharmaceutical granules: An experimental and numerical investigation
2013 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 49, no 2, 241-250 p.Article in journal (Refereed) Published
Abstract [en]

Granule shear behaviour was investigated experimentally and numerically to evaluate the reliability of the numerical model. Additionally, parameters affecting the ensuing flow regimes - elastic 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.

Keyword
Shear, Discrete element method, Flow regimes, Rolling friction, Shear rate
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-204131 (URN)10.1016/j.ejps.2013.02.022 (DOI)000319639800017 ()
Available from: 2013-07-22 Created: 2013-07-22 Last updated: 2017-12-06Bibliographically approved
3. An experimental evaluation of the accuracy to simulate granule bed compression using the discrete element method
Open this publication in new window or tab >>An experimental evaluation of the accuracy to simulate granule bed compression using the discrete element method
2012 (English)In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, no 219, 249-256 p.Article in journal (Refereed) Published
Abstract [en]

In this work, granule compression is studied both experimentally and numerically with the overall objective of investigating the ability of the discrete element method (DEM) to accurately simulate confined granule bed compression. In the experiments, granules of microcrystalline cellulose (MCC) in the size range 200-710 mu m were used as model material. Unconfined uniaxial compression of single granules was performed to determine granule properties such as the yield pressure and elastic modulus and compression profiles of the MCC granules were obtained from granule bed compression experiments. By utilizing the truncated Hertzian contact model for elastic-perfectly plastic materials, the rearrangement and plastic deformation stages of the force displacement curve were found to be in reasonable agreement with experiments. In an attempt to account for the final compression stage, elastic deformation of the compact, a simple modification of the contact model was proposed. This modification amounted to the introduction of a maximal plastic overlap, beyond which elastic deformation was the only deformation mode possible. Our results suggest that the proposed model provides an improved, although not perfect, description of granule bed compression at high relative densities and hence may be used as a basis for future improvements.

Keyword
Compression, Discrete element method, Contact model, Plastic overlap, Elastic deformation
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-172045 (URN)10.1016/j.powtec.2011.12.054 (DOI)000301310400033 ()
Available from: 2012-04-02 Created: 2012-04-01 Last updated: 2017-12-07Bibliographically approved
4. On the role of bulk modulus and granule hardness on the simulation accuracy of confined bulk granule compression
Open this publication in new window or tab >>On the role of bulk modulus and granule hardness on the simulation accuracy of confined bulk granule compression
(English)Manuscript (preprint) (Other academic)
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-208807 (URN)
Available from: 2013-10-08 Created: 2013-10-08 Last updated: 2014-01-23
5. The degree of compression of spherical granular solids controls the evolution of microstructure and bond probability during compaction
Open this publication in new window or tab >>The degree of compression of spherical granular solids controls the evolution of microstructure and bond probability during compaction
Show others...
2013 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 442, no 1-2, 3-12 p.Article in journal (Refereed) Published
Abstract [en]

The effect of degree of compression on the evolution of tablet microstructure and bond probability during compression of granular solids has been studied. Microcrystalline cellulose pellets of low (about 11%) and of high (about 32%) porosity were used. Tablets were compacted at 50, 100 and 150 MPa applied pressures and the degree of compression and the tensile strength of the tablets determined. The tablets were subjected to mercury intrusion measurements and from the pore size distributions, a void diameter and the porosities of the voids and the intra-granular pores were calculated. The pore size distributions of the tablets had peaks associated with the voids and the intra-granular pores. The void and intra-granular porosities of the tablets were dependent on the original pellet porosity while the total tablet porosity was independent. The separation distance between pellets was generally lower for tablets formed from high porosity pellets and the void size related linearly to the degree of compression. Tensile strength of tablets was higher for tablets of high porosity pellets and a scaled tablet tensile strength related linearly to the degree of compression above a percolation threshold. In conclusion, the degree of compression controlled the separation distance and the probability of forming bonds between pellets in the tablet. 

Keyword
Tablets, Pore structure, Microstructure, Degree of compression, Tensile strength, Percolation theory
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-196531 (URN)10.1016/j.ijpharm.2012.08.011 (DOI)000314690200002 ()
Available from: 2013-03-13 Created: 2013-03-11 Last updated: 2017-12-06Bibliographically approved

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