Scale-up Effects On the Growth Kinetics in High-Shear Wet Granulation: a Case Study

Scale-up of high-shear wet granulators is currently difficult to perform and there are no universally applicable scale-up rules. It is not completely clear how changes in granulator geometry and processing conditions can affect the granule growth [1]. An investigation on the scale-up effects on the growth behaviour in high-shear wet granulation is here described. Firstly, a mixture of some common-used pharmaceutical powders was processed using a top-driven, small scale granulator (2 l vessel volume). The processing conditions were systematically changed in order to arrange reproducible liquid dispersion conditions and nucleation regimes [2]. Secondly, the same powder mixture was processed using a pilot plant scale, bottom-driven granulator (65 l vessel volume). The dimensionless spray flux concept was used in order to keep the same liquid dispersion conditions [2]. The Focused Beam Reflectance Measurement Probe (FBRM) was used in combination with other particle size distribution measurement techniques (e.g. sieve analysis, laser diffraction methods) in order to carry out a detailed analysis of the growth behaviour. As already demonstrated by Cavinato et al. [3], this technique presents a good degree of accuracy and reproducibility. Results clearly showed the effect of the change in the granulator geometry and scale on the liquid distribution and, thus, the growth kinetics. A modification of the dimensionless spray flux number was furthermore proposed in order to best describe the phenomena and improve the predictability of the method.

[1] P. R. Mort, Scale-up of binder agglomeration processes, Powder Technology 150 (2005) 86-103. [2] J.D. Litster, K.P. Hapgood, J.N. Michaels, A. Sims, M. Roberts, S.K. Kameneni, T. Hsu, Liquid distribution in wet granulation: dimensionless spray flux, Powder Technology 114 (2001) 32–39. [3] M. Cavinato, D. Kayrak-Talay, J.D. Litster, Predicting the growth kinetics based on the formulation properties in high shear wet granulation, World Congress on Particle Technology, Nuremberg 25-29 April 2010.