283287 Characterization of Powder Mixing From Bench Scale to Commercial Scale with a Kinetic Model and NIR

Wednesday, October 31, 2012
Hall B (Convention Center )
Weixian Shi, Commercial Oral Technology & Operations, Bristol-Myers Squibb, New Brunswick, NJ, Rhye Hamey, PD, Bristol-Myers Squibb, New Brunswick, NJ and Dimuthu A. Jayawickrama, Analytical and Bioanalytical Development, Bristol-Myers Squibb, New Brunswick, NJ

The current study presents a method to characterize powder mixing and provides quantitative prediction of mixing performance upon scaling up.  The method unified a kinetic model (presented in 2010 Annual meeting) and a NIR on-line measurement model of a key ingredient (an active pharmaceutical ingredient or API, Compound X). Using this method, we quantified the driving force for mixing, or the shear energy, at various manufacturing scales. The quantification confirmed that that the shear energy increased upon scaling up from the bench scale to the pilot scale and to the commercial scale. Additionally, we monitored changes in the resistance for mixing, or cohesive energy, of Compound X at commercial scales with the same method. The variation in the cohesive energy of Compound X reflected the batch-to-batch fluctuation in the powder properties when the API was manufactured.  With the current method and a small sample from a new batch of API, we can predict the impact of such variation on the mixing performance of the new batch of API at various scales.   The cohesive energy of the new batch of API is measured at the bench scale and then plugged into the kinetic model with the shear energy at the scale of interest for prediction. The assumptions are 1) cohesive energy is an intrinsic material property and is scale independent; 2) shear energy is scale dependent but constant if mixing is operated with the same process parameters and formulation.

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