ABSTRACT
In the pharmaceutical industry, commercialization of a newly developed product or expansion of production capacity requires a scale-up of the production facilities. A change in scale changes process conditions and, consequently, the product attributes. However, regulatory policies dictate that key product properties must be maintained during scale-up to ensure the same application performances of the product. This poses a great technical challenge. This chapter examines the scaling-up approaches with the fundamental engineering principle of similitude. It analyzes the pharmaceutical granulation processes from the perspective of dominant rate processes that control the key attributes of the product granules. Specifically, it considers in detail the dominant rate processes and their associated dimensionless numbers in fluid-bed, high-shear mixer, and twin-screw granulation processes that are commonly used in the pharmaceutical industry. Using the similitude principles, the chapter recommends general scaling rules of maintaining the dominant rate processes and the related dimensionless numbers invariant during scale-up of the granulation processes to achieve the same product attributes.
