Scale-Down Wet Granulation Processing Challenges During Manufacture of Phamaceutical Solid Dosage Forms

Scale-up methodolgies for granulation processes have been significantly discussed within the literature. Dimensionless numbers, such as power number, that utilize geometric dimensions as well as impeller power consumption or torque are frequently used. Constants which generally relate to the geometric aspects of a granulator must usually be determined empirically for each granulator. Significant challenges in scaling exist when the bowl size is so small that wall effects dominate, as wall surface area to volume cannot be maintained. This work focuses on theoretical and practical aspects of wet granulating scaleup. Fundamental physical phenomena occurring in the granulator are evaluated. It evaluates the scale-down of a given formulation from a commercial-scale granulator to a 6-10 L lab-scale granulator, to determine if a scaling model can be developed for a scaledown of one to two orders of magnitude. Granulation properties are evaluated as a response, and Quality by Design control strategies for granulation are investigated.