Scale-up of Superficial Fluidization Air Velocity for a Pharmaceutical Fluid Bed Granulation

Fluid bed granulation is a common unit operation in pharmaceutical manufacturing.  Although the technology is mature, the complexity of the solid-fluid system has left incomplete scale-up principles.  In the current study, fluidizing air velocity scaling techniques are examined across equipment design, equipment scale, and batch size.  The scale of the current study ranges from 10-20 kg pilot-scale studies to 500 kg commercial scale batches.  We find that scaling superficial air velocity at the top of the fluidized bed (v_TOB) provides a more robust process scaling than at the distributor plate, which is commonly used.  Additionally, a dimensional analysis is performed for general fluid bed granulations to identify 5 relevant dimensionless groups which are interpreted to describe scale-up of process moisture, fluidizing air velocity (2), bowl fill, and total spray time.  We find conflicting guidance from 2 dimensionless groups for scaling fluidization air, but constant v_TOB represents a compromise between the two.  Together, these analyses led to a unique experimental design for a 500 kg scale developmental drug product campaign.