An investigation on the evolution of granule formation by in-process sampling of a high shear granulator

Abstract

Understanding the growth mechanisms in granulation process is an important topic, providing valuable insights and supports control strategies. Typically, observations in high shear granulators are made after stopping the process. In this work, an in-process sampling technique is described and applied to a high shear wet granulation process. Different samples can be collected over the cause of the high shear granulation process. This allowed observation of the evolution of granules during addition of water at a constant flowrate. For a typical pharmaceutical formulation, we observed that granules nucleate in the first 2min after starting the water addition and then grow to an average size of 200–1200μm at 12.5min, corresponding to a sharp increase in torque. Longer water addition times lead to oversized granules and eventually a paste and highly fluctuating torque. Sampling was also continued after stopping water addition which showed with time larger formed granules smoothen, whilst the smaller ones disintegrate. The work shows the in-process sampling can facilitate the identification of the granule growth kinetics and required binder quantity in high shear granulation.