Coupling granule properties and granulation rates in high-shear granulation

In this study, a hybrid multi-scale model has been developed for a continuous fluid bed wet granulation process by dynamically coupling computational fluid dynamics (CFD) with a discrete element model (DEM) and population balance model (PBM). In this process, the granules are formed by spraying the liquid binder on the fluidized powder bed. The fluid flow field has been solved implementing CFD principles and the behavior of the solid particles has been modeled using DEM techniques whereas the change in particle size has been quantified with the help of PBM. The liquid binder droplets have been modeled implicitly in DEM. A detailed understanding of the process aids in the development of better design, optimization and control strategies. The model predicts the evolution of important process variables (i.e., average particle diameter, particle size distribution (PSD) and particle liquid content) over time, which have qualitative similarity with experimentally observed trends. The advantage of incorporating the multi-scale approach is that the model can be used to study the distributions of collision frequencies, particle velocity and particle liquid content in different sections of the fluid bed granulator (FBG), in a more mechanistic manner.

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“…A simple expression (as shown in Equation (13)) has been adapted for collision efficiency based on the works of Biggs et al [47]:…”

Section: Population Balance Model For Fbgmentioning

confidence: 99%

A Multi-Scale Hybrid CFD-DEM-PBM Description of a Fluid-Bed Granulation Process

et al. 2014

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“…in an aggregation 25 only model, a two-dimensional population balance can be presented where collision is dependent only on 26 particle size but aggregation is dependent on both particle size and surface wetness (or stickiness). Similarly, 27 Biggs et al [42] used a pseudo two-dimensional (2-D) PBM that allowed composition on a size-averaged 28 basis to be modelled and coupled to the GSD. Verkoeijen et al [43] proposed a formulation of the multi-…”

mentioning

confidence: 99%

“…ulation models, Sanders et al [55] and Biggs et al [42] tried to model breakage as a negative aggregation 20 rate process, by reporting a reduced aggregation rate constant. However, this approach had serious flaws,…”

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confidence: 99%

“…While this approach may work in theory, its increased computation time and 18 complexity limits its applicability. A practically more feasible strategy is that a high-dimensional PBM can 19 be reduced to several simpler models of lower dimension [42,77,78]. In a reduced order model, one or more 20 granule characteristics are lumped into the remaining distributions.…”

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confidence: 99%

“…where, the granule is represented by total volume, granules of a given size have the same liquid content, as follows [42]:…”

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confidence: 99%

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

Kumar

Gernaey

Beer

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

106

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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 of 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 * Email address: ingmar.nopens@ugent.be, Tel.: +32 (0)9 264 61 96; fax: +32 (0) 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.

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Product Design of Particles

2014

Industrial Product Design of Solids and Liquids

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Coupling granule properties and granulation rates in high-shear granulation

Cited by 72 publications

References 6 publications

A Multi-Scale Hybrid CFD-DEM-PBM Description of a Fluid-Bed Granulation Process

A Multi-Scale Hybrid CFD-DEM-PBM Description of a Fluid-Bed Granulation Process

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

Product Design of Particles

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