Scale-up of a high shear wet granulation process using a nucleation regime map approach--颗粒学报PARTICUOLOGY

Luo, G., Xu, B., Zhang, Y., Cui, X., Li, J., Shi, X., & Qiao, Y. (2017). Scale-up of a high shear wet granulation process using a nucleation regime map approach. Particuology, 31, 87-94. https://doi.org/10.1016/j.partic.2016.04.007

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

Gan Luo^{a b 1}, Bing Xu ^{a c 1}, Yi Zhang ^{a 1}, Xianglong Cui ^a, Jianyu Li ^a, Xinyuan Shi ^{a c}, Yanjiang Qiao ^{a c *}

a Research Center of Traditional Chinese Medicine Information Engineering, Beijing University of Chinese Medicine, Beijing 100029, China
b Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, Beijing 100700, China
c Beijing Key Laboratory of Traditional Chinese Medicine Manufacturing Process Control and Quality Evaluation, Beijing Municipal Science & Technology Commission, Beijing 100029, China

10.1016/j.partic.2016.04.007

Volume 31, ,, April 2017, Pages 87-94

Received 15 December 2015, Revised 29 February 2016, Accepted 28 April 2016, Available online 28 September 2016, Version of Record 9 March 2017.

E-mail: yjqiao@bucm.edu.cn; yjqiao@263.net

Highlights

• The scale up of high shear wet granulation (HSWG) process was conducted by a regime map approach.

• Granule properties were evaluated to examine the similarity of granules of different scales.

• SeDeM method was applied to quantify the suitability of the granules for direct compression.

• The application of nucleation regime map to scale up HSWG process was feasible.

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 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.

Graphical abstract

Keywords

High shear wet granulation; Quality by design; Regime map; Scale-up; Microcrystalline cellulose

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