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Flowability of surface modified pharmaceutical granules: A comparative experimental and numerical study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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.

Place, publisher, year, edition, pages
2011. Vol. 42, no 3, 199-209 p.
Keyword [en]
Discharge rate, Angle of repose, Discrete element method, Rolling and sliding friction, Cohesion
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-149033DOI: 10.1016/j.ejps.2010.11.011ISI: 000287616300004PubMedID: 21112389OAI: diva2:403906
Available from: 2011-03-15 Created: 2011-03-15 Last updated: 2014-01-23Bibliographically approved
In thesis
1. Flow and Compression of Granulated Powders: The Accuracy of Discrete Element Simulations and Assessment of Tablet Microstructure
Open this publication in new window or tab >>Flow and Compression of Granulated Powders: The Accuracy of Discrete Element Simulations and Assessment of Tablet Microstructure
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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 180
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
urn:nbn:se:uu:diva-208808 (URN)978-91-554-8769-0 (ISBN)
Public defence
2013-11-22, B42, BMC, Husargatan 3, Uppsala, 09:15 (Swedish)
Available from: 2013-10-30 Created: 2013-10-08 Last updated: 2014-01-23

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