Novel methodology to assess and predict segregation risk in a continuous direct compression via mini-batch blending...

A methodology to assess and predict powder segregation in a Continuous Direct Compression via Mini-Batch Blending (cDC via MBB) process was developed using a representative test rig. A total of 44 formulations, including active pharmaceutical ingredients (APIs) and excipients at drug loads ranging from 5% to 40%, were investigated to span a broad material property space. Segregation behaviour was quantified using particle size distributions derived from samples collected along the rig outlet. A multivariate analysis identified a strong correlation between segregation intensity (SID₅₀) and the flow function coefficient (ffc). Based on this observation, an empirical linear relationship was established linking segregation tendency to flowability. To provide a pharmaceutically relevant measure, a secondary model was developed using chemical assay data, where segregation was quantified as the change in standard deviation of API concentration (Δstd) between the inlet and outlet of the rig. This model relates segregation behaviour to two measurable bulk properties: flow function coefficient and bulk density. The proposed approach provides a practical framework for early-stage assessment of segregation risk in cDC processes using limited material quantities. While the model is specific to the studied system, the methodology may be applicable to other powder handling processes subject to further validation.