268801 Scale-up of Superficial Fluidization Air Velocity for a Pharmaceutical Fluid Bed Granulation

Monday, October 29, 2012: 2:19 PM
Shadyside (Omni )
Brendon G. Ricart, Pharmaceutical Commercialization Technology, Merck & Co., West Point, PA, Alan R. Silverman, Pharmaceutical Commercialization Technology, Merck & Co., Inc., West Point, PA, Kristin J. Ploeger, Pharmaceutical Commercialization Technology, Merck & Co, Lansdale, PA and Edward J. Smith, Merck & Co., Inc., West Point, PA

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 (vTOB) 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 vTOB represents a compromise between the two.  Together, these analyses led to a unique experimental design for a 500 kg scale developmental drug product campaign.

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See more of this Session: Pharmaceutical Process Development & Pilot Plants
See more of this Group/Topical: Process Development Division