Modeling and characterization of intra-vial heterogeneity of lyophilized products using X-ray computed tomography.

This paper proposes a systematic work process for the rapid determination of the mass transfer resistance to vapour flow through the dry layer, which couples mathematical modelling and 3D non-destructive X-ray imaging to reconstruct the internal structure of lyophilised samples. This method was validated for mannitol-based formulations using various freezing protocols. This stepwise approach can then be used to design both freezing and primary drying step allowing lyophilisation professionals, on the one side, to reduce intra-vial heterogeneity and, on the other side, to optimize the drying step.