摘要
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 4 L 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 700 s, 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.
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 4 L 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 700 s, 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.
基金
The authors acknowledge research funding support from the Beijing Natural Science Foundation of China： study on the dimensionless modeling of high shear wet granulation process for Tanshinone extract （No. 7154217）, joint development program funding from the Beijing Municipal Education Commission of China （Key Laboratory Construction Project： study on the integrated modeling and optimization technology of the pharmaceutical process of Chinese medicine preparations）, and the program funding from the National Natural Science Foundation of China： study on the quality transfer model and global optimization method of the chained pharmaceutical process of Chinese medicine products （No. B1403112）.
