Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production - A critical review

Ashish Kumar, Krist Gernaey, Thomas De Beer, Ingmar Nopens

Research output: Contribution to journalJournal articleResearchpeer-review

1 Downloads (Pure)


The manufacturing of pharmaceutical dosage forms, which has traditionally been a batch-wise process, is now also transformed into a series of continuous operations. Some operations such as tabletting and milling are already performed in continuous mode, while the adaptation towards a complete continuous production line is still hampered by complex steps such as granulation and drying which are considered to be too inflexible to handle potential product change-overs. Granulation is necessary in order to achieve good flowability properties and better control of drug content uniformity. This paper reviews modelling and supporting measurement tools for the high shear wet granulation (HSWG) process, which is an important granulation technique due to the inherent benefits and the suitability of this unit operation for the desired switch to continuous mode. For gaining improved insight into the complete system, particle-level mechanisms are required to be better understood, and linked with an appropriate meso- or macro-scale model. A brief review has been provided to understand the mechanisms of the granulation process at micro- or particle-level such as those involving wetting and nucleation, aggregation, breakage and consolidation. Further, population balance modelling (PBM) and the discrete element method (DEM), which are the current state-of-the-art methods for granulation modelling at micro- to meso-scale, are discussed. The DEM approach has a major role to play in future research as it bridges the gap between micro- and meso-scales. Furthermore, interesting developments in the measurement technologies are discussed with a focus towards inline measurements of the granulation process to obtain experimental data which are required for developing good models. Based on the current state of the developments, the review focuses on the twin-screw granulator as a device for continuous HSWG and attempts to critically evaluate the current process. As a result, a set of open research questions are identified. These questions need to be answered in the future in order to fill the knowledge gap that currently exists both at micro- and macro-scale, and which is currently limiting the further development of the process to its full potential in pharmaceutical applications.
Original languageEnglish
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number3
Pages (from-to)814-832
Publication statusPublished - 2013

Fingerprint Dive into the research topics of 'Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production - A critical review'. Together they form a unique fingerprint.

Cite this