Impact of impeller design on high-shear wet granulation

Abstract In recent decades, three-blade impellers have been well-established in pharmaceutical high-shear granulation. However, three-blade impellers often require high rotation speeds to initiate product circulation and to provide proper granulation performance. With high rotation speeds much energy is introduced, which is indeed favourable for granule consolidation, however it comes with undesirable thermal stressing and increased granule breakage rates. In order to improve the mixing and granulation behaviour for a more robust process, a new impeller design has been developed that works at lower rotation speeds. The impeller consists of two blades with elongated side wings. In this work, the performance of both impeller designs is intensively studied. Firstly, the mixing behaviour is experimentally investigated in a laboratory mixer (10 L in volume) and at production scale (600 L). The mixing homogeneity of coloured sugar pellets is examined by the digital image analysis (DIA) for several impeller rotation speeds. In a second study, discrete element method (DEM) simulations are employed to obtain shear forces and force distributions at a single-particle scale. The third study is the comparison of granulation performance using a placebo formulation in the frame of a full factorial design of experiments (DoEs). The mixing investigations show that the two-blade impeller has great potential for scale-up. The DEM simulation confirms that both impeller types investigated apply almost the same shear forces on particles. The granulation performance in the DoE is proven to be better for the two-blade impeller. Larger drive torque is measured, product temperature increases significantly less with reduced thermal stressing, and larger granules are produced. Additionally, particle growth behaviour is more robust as it depends only on the amount of liquid added and is unaffected by the impeller's rotation speed.