Scale-up of mixer granulators for effective liquid distribution
Introduction
Granulation is the process of agglomerating fine powdery materials using a liquid binder to give larger granules. This can be achieved in a range of different processing equipment including drums, pans, fluid beds and high shear mixers. It is an important process in a range of industries including agricultural chemicals, pharmaceuticals, mineral processing, food and detergents.
Wet granulation is complex. Many phenomena occur simultaneously in the granulator which will influence the granule attributes. We divide these into three groups [1]:
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Granule nucleation and binder distribution
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Granule consolidation and growth
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Granule attrition and breakage
This paper focuses on the first mechanism of nucleation and binder distribution. An understanding of binder dispersion is a crucial step towards controlling granule properties. The degree of binder dispersion indicates the quality of the mixing between the powder and the binder fluid, and is reflected in the product size distribution [2].
There is considerable anecdotal evidence from industry that poor wetting and liquid distribution can lead to broad granule size distributions in mixer granulators. Current scale-up scenarios lead to poor liquid distribution and a wider product size distribution. There are two issues to consider when scaling up: the size and nature of the spray zone and the powder flow patterns as a function of granulator scale.
Many variables affecting binder dispersion and nucleation have already been identified. Binder dispersion is aided by lower binder flowrate [3], [4], atomisation of the binding fluid [4], [5], [6], [7], [8], [9], [10], large spray zone (higher spray angles and high nozzles) [11], [12], [13] and high powder flux through the spray zone [3], [14]. Frequent contradictions in results between these workers demonstrate the strong dependence on particular equipment set-ups [13] and that an equipment-independent parameter or controlling group is needed to reliably describe the nucleation zone conditions.
An attempt to describe the nucleation zone conditions across equipment scales has been made by Tardos et al. [14] and Watano et al. [15]. They suggest measuring binder delivery in terms of the binder flowrate compared to the size of the spray zone and the powder flux through the spray zone. They measured the granule size and size distribution as a function of gas velocity, spray zone size and equipment scale. In this case, increasing the gas velocity will increase the powder turnover and the powder flux through the spray zone. All experiments used an identical spray nozzle, but the relative size of the spray zone compared to the bed volume decreased as the granulator was scaled up. The best binder dispersion and consequently the narrowest distribution was produced with a high gas flowrate at the smallest scale, i.e. the highest powder turnover and the largest spray zone.
Effective liquid distribution must be quantified over a range of scales to maintain good wetting. In the case of atomised binder addition, the three main operating variables in the spray zone are flowrate, drop size and powder flux through the spray zone. A dimensionless group involving three parameters was defined in a previous paper [16]. The dimensionless spray flux Ψa is a measure of the area flux of drops from the nozzle compared to the flux of powder surface through the spray zone, and is defined as [16]:where V̇ is the volumetric spray rate, dd is the droplet diameter, and Ȧ is the area flux of powder traversing the spray zone. A low spray flux means well-dispersed droplets and controlled nucleation where one drop forms one nuclei (drop-controlled regime). The drop-controlled regime implicitly assumes that the drop size is larger than the powder particle size. High spray flux means high spray density and agglomeration of spray drops on the powder surface leading to a broader, more difficult to control nuclei distribution [16]. Very high spray flux leads to caking of the powder surface and requires shear forces to re-disperse the binder liquid (mechanical dispersion-controlled regime). Dimensionless spray flux promises to be a useful parameter for maintaining equivalent liquid distribution across different scales of granulator.
The Ψa group was previously validated using ex-granulator experiments where a bed of powder was passed once beneath a spray nozzle. In this paper, we investigate the relationship between Ψa and the nuclei size distribution in an industrial high shear granulator by spraying at short times. To calculate Ψa values in the granulator, separate experiments to measure powder velocities in the spray zone as a function of impeller speed are described. Finally, we discuss the implications of Ψa on liquid distribution during scale-up.
Section snippets
Materials characterisation
Lactose monohydrate powder (Foremost Farms, Barbaroo, WI, USA) was prepared by screening over a 150-μm screen and discarding the +150-μm material. This allowed complete separation of granules (+180 μm) from the unwet powder (−150 μm) during sieve size analysis. Particle size analysis using a Microtrac SRA150 (Leeds and Northrup) gave a volume mean particle diameter of d43=69.2 μm and a surface mean size d32=17.9 μm. The true density of the particles was measured using Helium picnometer
Granulator flow regimes
Granulator flow patterns were measured for 6-kg dry lactose powder with impeller speeds from 100 to 500 rpm with chopper speeds of either 360 or 3600 rpm. We found that the powder bed did not fluidise and it was easy to follow a packet of powder by using the natural bed structure (lumps and cracks in the packed bed).
Two distinct flow regimes were observed. At low impeller speeds, the powder surface remained horizontal and the bed “bumped” up and down as the impeller passed underneath. Hiseman
Discussion
The powder velocity results were used to calculate Ψa at each set of conditions. Table 4 summarises the conditions, Ψa values and the d10, d50 and d90 of the nuclei immediately after spraying. The change in spray width with pressure has been included in calculations of Ψa. The experiments in the 25L PMA Fielder covered a wide range of Ψa values from 0.16 to 1.14. In general, the d10 size rises slightly as Ψa increases, but the d90 increases significantly with Ψa. This indicates the progressive
Scale-up implications
Both the powder flow regime (bumping or roping) and spray flux Ψa must be maintained across changes in granulator scale to successfully scale-up liquid distribution.
Clearly, the roping flow regime is best for good nucleation and liquid distribution. Powder surface velocity is highest in the roping regime and the improved bed turnover continuously presents fresh powder to the spray zone. In contrast, the bumping regime will recycle the same wet powder surface to the spray as the bed rotates
Conclusion
Short, nucleation-only experiments demonstrated the existence of different nucleation regimes depending on the spray flux Ψa—from drop-controlled nucleation to caking. The fraction of nuclei formed from two or more drops increased rapidly as Ψa increased above 0.2 causing the distribution to broaden rapidly. The results are in excellent agreement with previous ex-granulator experiments and confirm that for drop-controlled nucleation, Ψa should be less than 0.1.
Flow studies identified two powder
Acknowledgements
This project was funded by an Australian Research Council grant, International Fine Particles Research Institute, and by Merck & Co. Thanks to Reid Zeigler, of Merck & Co., for assistance with high speed video imaging of powder flow. Thanks also to Maria Cruanes, Larry Rosen, Jim Zega and Udit Batra of Merck & Co. for their discussion and ideas during the project.
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