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30 January 2018 Tablets & Capsules S x and S y are the granulators' internal wall surface areas, and V x and V y are their bulk mass volumes. Know your process High-shear granulation scale-up is still a hit-and-miss process, requiring much trial and error. However, recent developments have removed some of the art in this process, in turn injecting science into the decision- making process. The ultimate goal of granulation research is to be able to design granulation processes to give the desired granule properties without requiring lab- scale trials and scale-up. However, while we've seen advances, this goal is still a long way off. The most important part of scale-up is to know your process and use this knowledge in your decisions. T&C References 1. S.M. Iveson, J.D. Litster, et al., "Nucleation, growth and breakage phenomena in agitated wet granulation processes: A review," Powder Technology, 2001, Vol. 117, No. 1-2, pages 3-39. 2. J. Litster and B. Ennis, The Science and Engineering of Granulation, Kluwer Academic Publishers, 2004. 3. G.I. Tardos, K.P. Hapgood, et al., "Stress measurements in high-shear granulators using calibrated 'test' particles: Application to scale-up," Powder Technology, 2004, Vol. 140, No. 3, pages 217-227. 4. G.K. Reynolds, P.K. Le, et al., "High-shear granulation," in Granulation (Handbook of Powder Technology), edited by A.D. Salman, M.J. Hounslow, and J.P.K. Seville, Elsevier, 2007. 5. K.P. Hapgood, J.D. Litster, et al., "Nucleation regime map for liquid bound granules," AIChE Journal, 2003, Vol. 49, No. 2, pages 350-361. 6. N. Rahmanian, B.H. Ng, et al., "Scale-up of high- shear mixer granulators," KONA Powder and Particle Journal, 2008, No. 26, pages 190-204. Rachel Smith is a senior lecturer in the Department of Chemical and Biological Engineering at the University of Sheffield, Mappin Street, Sheffield, S1 3JD, UK. Tel. +44 114 222 8255 (rachel.smith@sheffield.ac.uk). She holds a BEng and a PhD in chemical engineering, both from the University of Queensland, Brisbane, Queensland, Australia. She's been working in the fields of granulation and particle technology for 18 years. A version of this article first appeared in the June 2012 issue of Powder and Bulk Engineering. scale-up changes have caused an increase in granule size, increasing chopper speed may help reduce granule size. Binder addition method and flow rate Advances in granulation research have led to the development of the nucleation regime map, a tool describing the type of nucleation behavior that can be expected in a given granulation process [5]. This map has two dimensionless parameters: the dimensionless drop penetration time (the time for a liquid binder drop of characteristic size to fully immerse into the bulk powder) and the dimensionless spray flux, which can be thought of as the ratio between the liquid spray rate and the particle turnover rate at the powder bed surface. Low drop penetration time (that is, quickly penetrating drops) and low spray flux (that is, drops that are well spread out on the powder surface) place the nucleation behavior in the drop-controlled regime, which means that most of the nuclei will be formed from a single droplet, resulting in a narrow nuclei size distribution. High values of either drop penetration time or spray flux will lead to over-wetting and liquid pooling at the powder bed surface, creating large nuclei that require mechanical forces to disperse. This is known as the mechanical dispersion regime and leads to a wide nuclei distribution. In essence, the nuclei size distribution is the granulation starting point, and for many formulations it's important to form similar nuclei size distribution across the granulator length. If the granulation process you're scaling up from operates in the drop-controlled regime, it would be beneficial to design the spray nozzle for the larger-scale process so that the drop size is similar to the original scale (maintaining similar drop penetration time) and the dimensionless spray flux remains low (resulting in single- drop nuclei). Methods to reduce the spray flux ensure that the spray width covers the powder bed's available surface (that is, the granulator's radius), reducing the liquid binder's volumetric flow rate and increasing the powder velocity. Granulation time It's difficult to know how granulation time will affect granule properties across different granulator lengths. Mechanical distribution of the liquid binder may take longer in a larger granulator; however, this will largely depend on your formulation and other operating parameters. One recommended method to scale granulation time in the granulator is to use the relationship described by the equation below [6]: where x is the original granulator, y is the scaled-up granulator, t x and t y are the units' granulation times, t x t y S y V x S x V y ( ) ( ) =