Experimental analysis of inter- and intra-batch variation of granule porosity, stiffness and dissolution rate
File(s)manuscript.pdf (1.64 MB)
Accepted version
Author(s)
Smrcka, David
Lesakova, Veronika
Dohnal, Jiri
Grof, Zdenek
Stepanek, Frantisek
Type
Journal Article
Abstract
Using a pharmaceutical formulation, granule batches were produced at a range of granulator volumes from 0.5 L to 400 L and process conditions, characterised by the Froude number in the range from Fr = 0.26 to Fr = 1.63. The mean values and the standard deviations of granule porosity, granule stiffness and granule dissolution rate evaluated from each batch using the 400–1000 μm sieve fraction were compared in order to establish structure–property correlations. Both granule stiffness and granule dissolution rate were found linearly correlated with the Froude number. A significant intra-batch variability of all investigated granule properties was observed. The relative standard deviation of granule stiffness also increased linearly with the Froude number. Coupled experiments relating the microstructure of granules with their individual compression and dissolution curves were carried out for the first time. A surprising diversity of intra-batch granule structures and their associated dissolution rates was found in batches produced at both low and high Froude numbers, highlighting the importance of avoiding granule segregation in downstream unit operations in order to maintain consistent drug release profiles from the investigated formulation.
Date Issued
2018-04-01
Date Acceptance
2018-02-06
Citation
CHEMICAL ENGINEERING RESEARCH & DESIGN, 2018, 132, pp.1131-1142
ISSN
0263-8762
Publisher
INST CHEMICAL ENGINEERS
Start Page
1131
End Page
1142
Journal / Book Title
CHEMICAL ENGINEERING RESEARCH & DESIGN
Volume
132
Copyright Statement
© 2018 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000430522300096&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Technology
Engineering, Chemical
Engineering
Porosity
X-ray micro-tomography
High-shear wet granulation
Texture analysis
Single granule dissolution
Froude number
HIGH-SHEAR GRANULATION
WET GRANULATION
SCALE-UP
MICROSTRUCTURE
SIZE
TOMOGRAPHY
MORPHOLOGY
BREAKAGE
POWDERS
SPEED
Publication Status
Published
Coverage Spatial
Univ Sheffield, Sheffield, ENGLAND
Date Publish Online
2018-02-14