Application of definitive screening design to quantify the effects of process parameters on key granule characteristics and optimize operating parameters in pulsed-spray fluid-bed granulation--颗粒学报PARTICUOLOGY

Zhao, J., Li, W., Qu, H., Tian, G., & Wei, Y. (2019). Application of definitive screening design to quantify the effects of process parameters on key granule characteristics and optimize operating parameters in pulsed-spray fluid-bed granulation. Particuology, 43, 56-65. https://doi.org/10.1016/j.partic.2018.03.007

Application of definitive screening design to quantify the effects of process parameters on key granule characteristics and optimize operating parameters in pulsed-spray fluid-bed granulation

Jie Zhao ^a, Wenlong Li ^a, Haibin Qu ^a *, Geng Tian ^b, Yanding Wei ^b *

a Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
b Key Laboratory of Advanced Manufacturing Technology of Zhejiang Province, College of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China

10.1016/j.partic.2018.03.007

Volume 43, April 2019, Pages 56-65

Received 18 July 2017, Revised 22 November 2017, Accepted 1 March 2018, Available online 26 July 2018, Version of Record 19 February 2019.

E-mail: quhb@zju.edu.cn; weiyd@zju.edu.cn

Highlights

• A novel definitive screening design was used to investigate the granulation process.

• Quantified the relationships between studied factors and critical quality attributes.

• The differing and peculiar roles of six critical process parameters were interpreted.

• A design space for the pulsed spray fluid bed granulation was determined.

Abstract

The pulsed-spray fluid-bed granulation (PSFBG) process was investigated and optimized using definitive screening design, a recently proposed new class of three-level design of experiment method. Such a design enabled quadratic models to be established that described the effect of six input process parameters – inlet air temperature, inlet air humidity, binder spray rate, atomization pressure, pulse period, and pulse width – on the granule quality in a PSFBG process. Mathematical models of the mean particle size, relative size distribution width, production yield, and porosity were developed to quantify the relationships between the influencing factors and critical quality attributes. On the basis of constraints on the desired granule properties, a design space for PSFBG was determined and ranges of the operating parameters were defined. An acceptable degree of prediction was confirmed by validation experiments, demonstrating the reliability and effectiveness of using definitive screening design to study the PSFBG process. This method can accelerate screening and optimization of this process within a large multidimensional design space.

Graphical abstract

Keywords

Pulsed-spray fluid-bed granulation; Design of experiment; Definitive screening design; Mathematical models; Design space; Process parameters

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