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Steady states in granulation of pharmaceutical powders with application to scale-up
Version 2 2024-06-04, 10:59Version 2 2024-06-04, 10:59
Version 1 2017-04-06, 17:28Version 1 2017-04-06, 17:28
journal contribution
posted on 2024-06-04, 10:59 authored by JN Michaels, L Farber, GS Wong, Karen HapgoodKaren Hapgood, SJ Heidel, J Farabaugh, JH Chou, GI TardosTheoretical and experimental evidence is given to show that steady states can be reached during agglomerate growth and break-up in high-shear granulation of fine powders. An earlier theoretical model [G.I. Tardos, I.M. Khan and P.R. Mort, Critical parameters and limiting conditions in binder granulation of fine powders, Powder Technology, 94, 245-258 (1997).], based on simple energy-dissipation considerations hinted at the existence of these states at the point where growth is counterbalanced by breakage. Further theoretical evidence is obtained from molecular dynamic simulations of wet and dry particles situated in a constant shear field [I. Talu, G.I. Tardos and M.I. Khan, Computer simulation of wet granulation, Powder Technology, 110, 59-75 (2000).], where the size distribution of initially identical particles, shifts in time to reach a dynamic steady state. Under the conditions of this steady state, the number of breaking agglomerates approximately equals the number of forming ones to yield a time independent final-size distribution. Experimental evidence to support the theoretical findings is obtained during the present research by measuring particle size distributions at line at crucial points during granulation of a typical pharmaceutical powder in a high-shear mixer. In order to reach a steady state, binder addition has to be slow enough and wet massing has to be long enough so that neither has an influence on the final properties of the granules. We show experimentally that if binder is spread properly and homogeneously in the powder and continuous shearing of the wet mass ensures homogeneous, equal growth of the granules, the steady state will only be a function of the total amount of fluid added provided that the shear forces in the machine are maintained constant. These findings are important in that they show that under carefully controlled conditions of binder addition and shear in the mixer, the granulation process is robust and controllable and can, in principle, be scaled up with ease once the powder ingredients and the total amount of binder are fixed. © 2008 Elsevier B.V. All rights reserved.
History
Journal
Powder TechnologyVolume
189Pagination
295-303Location
Amsterdam, The NetherlandsPublisher DOI
ISSN
0032-5910Language
engPublication classification
C Journal article, C1.1 Refereed article in a scholarly journalCopyright notice
2008, Elsevier B.V.Issue
2Publisher
Elsevier B.V.Usage metrics
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