A systematic comparison of four pharmacopoeial methods for measuring powder flowability

Powder flow is one of the crucial factors affecting several pharmaceutical manufacturing processes. Problems due to insufficient powder flow reduce production process efficiency and cause suboptimum product quality. The U. S. Pharmacopoeia has specified four methods to evaluate the flowability of pharmaceutical powders, including angle of repose (AoR), compressibility index (CI) and Hausner ratio (HR), Flow through an orifice, and shear cell. Comparison within and between those methods with 21 powders (covering a wide range of flowability) was performed in this study. Strong correlation was observed between fixed base cone AoR, and fixed height cone AoR (R-2 = 0.939). CI and HR values calculated from a tapped density tester (meeting USP standards), manual tapping, and Geopyc (R) correlated strongly (R-2 > 0.9). AoR, CI/HR, minimum diameter for flowing through an orifice (dmin), and shear cell results generally correlate strongly for materials with flowability worse than Avicel (R) PH102. Both shear cell and CI/HR methods can reliably distinguish powders exhibiting poor flow. For materials with good flow, the ability to distinguish powders follows the order of AoR approximate to CI/HR > shear cell > dmin. The systematic comparison of the four common methods provides useful information to guide the selection of methods for future powder flow characterization. Given the limitations observed in all four methods, we recommend that multiple techniques should be used, when possible, to more holistically characterize the flowability of a wide range of powders.