Bulk Characterization of Pharmaceutical Powders by Low-Pressure Compression II: Effect of Method Settings and Particle Size

The aim of the present study was to investigate the effect of punch and die diameter, sample size, compression speed, and particle size on two low-pressure compression-derived parameters; the compressed density and the Walker w parameter. The excellent repeatability of the low-pressure compression method allowed small effects of variations in punch and die diameter and sample size to be demonstrated on a high significance level. Changing the compression speed, however, did not cause a significant effect in the compressed density, whereas a decrease in w was seen. The effect of particle size was studied by compressing and tapping different grades of calcium carbonate, lactose, and microcrystalline cellulose. The low-pressure compression-derived parameters were compared to tapped densities and to Compressibility Indexes obtained by tapping volumetry. Even though the relationship between particle size and the low-pressure compression-derived parameters appeared to be more complicated, a similar trend was observed. It was concluded that the low-pressure compression method provides a useful alternative to the more sample-consuming methods providing flow-related information.