Development and optimization of an LED-based particle image velocimetry methodology for dynamic powder flowability in pharmaceutical manufacturing.

Conventional static flowability tests lack the sensitivity to capture process-relevant powder dynamics. This study developed and optimized an LED-based particle image velocimetry (PIV) system for real-time, non-invasive characterization of powder dynamic flowability during blending. Three PIV parameters, illumination intensity, CLAHE window size, and interrogation window size, were systematically optimized; optimal conditions (65,125 lx; 16 px CLAHE; 32 px) yielded reproducible velocity vector fields. The system was applied to six excipients: three MCC grades (AvicelⓇ PH-102, PH-112, PROSOLVⓇ SMCC 50) and three lactose-based powders (CellactoseⓇ 80, TablettoseⓇ 80, MicroceLacⓇ 100), with complementary FT4 powder rheometer measurements. Multi-parametric analysis encompassing velocity magnitude, vorticity, shear strain rate, stretching deformation rate, and correlation coefficient across spatially defined regions of interest revealed powder-specific flow dynamics. Among MCC grades, PROSOLVⓇ SMCC 50 showed the highest velocity (0.99 px/frame), while AvicelⓇ PH-102 and PH-112 were comparable (0.32 px/frame each) yet differed 6-9-fold in blade-region vorticity and shear strain rate, representing mechanistic differences not discernible by static Carr's index. Among lactose-based powders sharing similar static classifications, PIV revealed distinct velocity profiles: MicroceLacⓇ 100 (0.78), CellactoseⓇ 80 (0.71), and TablettoseⓇ 80 (0.51 px/frame). FT4 cohesion and unconfined yield strength inversely correlated with PIV velocity (r = -0.97), corroborating the PIV-derived flowability rankings, whereas basic flowability energy did not predict blending performance, confirming that confined-condition metrics do not capture process-relevant dynamics. These results establish LED-based PIV as a practical, multi-dimensional flowability characterization tool, complementary to powder rheometry, with direct relevance to excipient selection and process design in pharmaceutical manufacturing.