Granule breakage phenomena in a high shear mixer; influence of process and formulation variables and consequences on granule homogeneity

Wet granulation is a process intended for size enlargement. A logical consequence is that many studies are focused on granule growth. However, next to built-up of granules granule breakage also occurs. The aim of this study is to investigate the wet granule breakage process in a high shear mixer. For that purpose, tracer experiments were conducted to investigate the influence of the particle size of lactose and the viscosity of the hydroxypropylcellulose (HPC) solution on the granule breakage. The relationship between granule breakage behaviour and granule homogeneity was also investigated. A model to predict granule breakage, based on the ratio of the impact energy and the dynamic granule strength, was proposed. The tracer experiments showed that an increase in viscosity and a decrease in particle size eventually lead to a transition from breakage to no-breakage behaviour of the granules. The model predicts similar influences of these parameters on the breakage behaviour and showed a clear relationship with the experimental data. Moreover, an interrelationship between granule breakage and homogeneity was found. The dynamic situation of granule breakage was associated with a continuous exchange of particles, which resulted in homogeneous granules. When granule breakage was absent granules remain intact and the preferential layering of the smallest particles yielded inhomogeneous granules.