Wet granulation in laboratory-scale high shear mixers: Effect of chopper presence, design and impeller speed

Abstract

The effect of the main means of agitation in a high shear mixer has been investigated in this study. Granulation runs have been performed on a fine cohesive microcrystalline cellulose powder (Avicel 105, d 50 = 20 μm) often used as a pharmaceutical excipient in tablet formulations in two bowls of a Mi-Pro® laboratory high shear mixer with a capacity of 0.9 and 1.9 L, respectively. Torque curves recorded during granulation are found to allow good control of the process while increasing impeller speed is found to generally reduce granule size and the onset of breakage seems to occur for similar values of impeller tip speed. As a general rule, the chopper allows for better binder distribution in the Mi-Pro® and is found to be necessary for successful granulation at low to moderate impeller speeds. For high impeller speeds in excess of 4.4 m/s with or without a chopper, similar granule sizes and growth mechanisms are observed. Granule roundness was found to increase with impeller speed up to a certain speed after which granule roundness has been found to decrease with increasing impeller speed most probably because of increased breakage of the granules. Dry granule strength has been found to increase with increasing impeller speed, presenting only a slight decrease at the highest impeller speed studied.

Process analytical technology (PAT) approach to the formulation of thermosensitive protein-loaded pellets: Multi-point monitoring of temperature in a high-shear pelletization

“…Benali et al (2009) determined in the case of between 40 and 150 rpm impeller speed the fine particle that the mean granules diameter increases with increasing impeller speed and in the case of impeller speed beyond 200 rpm the mean granules size decreases with increasing impeller speed. Chitu et al (2011) also found the granules size will decrease and the percentage of lumps will also decrease for high impeller seed.…”

“…Many authors (Benali et al, 2009;Chitu et al, 2011;Rahmanian et al, 2011) have studied the effect of impeller speed on granule/pellet properties. Diverse influences have been found: from almost independent granule/pellet size distributions (Rahmanian et al, 2011) to significantly affected granule/pellet size distributions in a way of reducing entity sizes (Chitu et al, 2011;Zizek et al, 2013).…”

The Effect of the Chopper on Granules from Wet High-Shear Granulation Using a PMA-1 Granulator

“…Holm (5) also found that the chopper had no effect on size distribution. Chitu et al (6) found that the effect of the chopper depends on the impeller speed. They granulated microcrystalline cellulose with water as a binder in a small scale MiPro mixer.…”

Application of Wet Granulation Processes for Granola Breakfast Cereal Production

“…Chitu et al [21], again using microcrystalline cellulose (MCC), reported the granule roundness was increased with impeller speed up to a certain speed, after which granule roundness was found to decrease with increasing impeller speed, most probably because of increased breakage of the granules. Dry granule strength has been found to increase with increasing impeller speed presenting only a slight decrease at the highest impeller speed studied.…”

“…While the chopper allows better binder distribution and is necessary for successful granulation at low to moderate impeller speeds [21], it can also lead to breakage. The effects of impeller and chopper speeds on granule homogeneity were studied by van den Dries et al [116].…”