A quality by design approach to scale-up of high-shear wet granulation process

Abstract

High-shear wet granulation is a complex process that in turn makes scale-up a challenging task. Scale-up of high-shear wet granulation process has been studied extensively in the past with various different methodologies being proposed in the literature. This review article discusses existing scale-up principles and categorizes the various approaches into two main scale-up strategies – parameter-based and attribute-based. With the advent of quality by design (QbD) principle in drug product development process, an increased emphasis toward the latter approach may be needed to ensure product robustness. In practice, a combination of both scale-up strategies is often utilized. In a QbD paradigm, there is also a need for an increased fundamental and mechanistic understanding of the process. This can be achieved either by increased experimentation that comes at higher costs, or by using modeling techniques, that are also discussed as part of this review.

• Impeller speed
• porosity
• quality by design
• scale-up
• wet granulation

Acknowledgements

The authors would like to thank Dilbir S. Bindra from Bristol-Myers Squibb and Anjali Agrawal from Boehringer Ingelheim Pharmaceuticals Inc. for providing useful feedback on this review.

Declaration of interest

The authors report no declarations of interest.