(243c) "One-Dimensional" Scale-up of High-Shear Granulators | AIChE

(243c) "One-Dimensional" Scale-up of High-Shear Granulators


Michaels, J. N. - Presenter, Merck and Co. Inc.
Wang, G. - Presenter, Merck and Co. Inc.
Farber, L. - Presenter, Merck & Co. Inc.
Tardos, G. I. - Presenter, The City College of the City University of New York
Hapgood, K. P. - Presenter, Merck and Co. Inc.
Chou, J. - Presenter, Merck and Co. Inc.
Heidel, S. - Presenter, Merck and Co. Inc.

This talk describes a simplified method for scaling of batch high-shear granulation. It is based on analysis of granule nucleation, consolidation, growth, and breakage by the research groups at the City University of New York and the University of Queensland. This analysis suggests that by operating batch granulation under conditions of low spray flux and balanced granule growth and breakage rates, the final particle size distribution should be a function only of the final liquid saturation and shear stress in the agitated wet mass. The fluid level appears in this analysis as a material variable rather than a process variable, e.g. it is scale-independent. Thus, the only process variable involved in scale-up is the shear stress, controlled by the main impeller speed, making scale-up a single-variable exercise. This concept was tested with a conventional pharmaceutical formulation in five vertical-axis high-shear granulators between 2-L and 300 L scale, using a correlation between shear stress and main impeller speed developed independently [1]. At low and moderate saturations, a quantitative match in granulation properties was achieved at all scales. At higher saturations, the scaling approach began to break down and show the influence of other variables that could not be independently controlled. Reasons for the deviation from the expected scaling behavior are discussed in an effort to highlight some fundamental issues in granulation that require continued study.


1. Tardos, G.I., K. P. Hapgood, O. O. Ipadeola and J. N. Michaels, ?Stress measurements in High Shear Granulators using calibrated ?test? Particles: application to Scale-up?, Vol. 140, pp. 217-227, Powder Technology, (2004).