Scale-up of a high shear wet granulation process using a nucleation regime map approach

Abstract

Scale-up of the high shear wet granulation (HSWG) process is considered a challenge because HSWG is complex and influenced by numerous factors, including equipment, formulation, and process variables. For a system of microcrystalline cellulose and water, HSWG experiments at three scales (1, 2, and 4L working vessel) were conducted with a granulator. Scale-up was implemented on the basis of a nucleation regime map approach. To keep dimensionless spray flux and drop penetration time constant, water addition time at three processing scales were 300, 442, and 700s, respectively. The other process parameters were kept unchanged. Granule size distributions were plotted and compared, and scanning electron microscopy was used to analyze granule surface morphology. Physical characterization was undertaken using a modified SeDeM method. At nearly all scales, granule yield was greater than 85% and all the cosine values were larger than 0.89. At the same experiment points, granules at all scales had similar surface morphology and similar physical characteristics. The results demonstrate that a rational scaling-up of the HSWG process is feasible using a regime map approach.