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Compressibility and tablet forming ability of bimodal granule mixtures: Experiments and DEM simulations
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.
2018 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 540, no 1-2, p. 120-131Article in journal (Refereed) Published
Abstract [en]

Compressibility and tablet forming ability (compactibility) of bimodal mixtures of differently sized granules formed from microcrystalline cellulose were studied experimentally and numerically with the discrete element method (DEM). Compression data was analysed using the Kawakita equation. A multi-body contact law that accounts for contact dependence resulting from plastic incompressibility/geometric hardening was used in the DEM simulations. The experimental Kawakita a and 1/b parameters both depended non-monotonically on composition (weight fraction of large particles). For the a parameter, this dependence was explained by variations in the porosity of the initial granule beds; for the 1/b parameter, other factors were found to be of importance as well. The numerical results generally compared favourably with the experiments, demonstrating the usefulness of the DEM at high relative densities, provided that a suitable multi-particle contact model is used. For all mixtures, the tensile strength of the formed tablets increased with increasing applied pressure. The tensile strength generally decreased with increasing fraction of large particle, and this decrease was more rapid for large differences in particle size. A possible interpretation of these findings was proposed, in terms of differences in lateral support of small particles in the vicinity of large particles.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV , 2018. Vol. 540, no 1-2, p. 120-131
Keywords [en]
Mixture, Compressibility, Compactibility, Tensile strength, Discrete element method
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-351563DOI: 10.1016/j.ijpharm.2018.02.006ISI: 000427584900013PubMedID: 29425765OAI: oai:DiVA.org:uu-351563DiVA, id: diva2:1210955
Available from: 2018-05-30 Created: 2018-05-30 Last updated: 2018-08-20

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Nordström, JosefinaAlderborn, GöranFrenning, Göran

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