Analysis of Powder Properties of Pharmaceutical Excipients Using a Constant-Volume Shear Tester

Abstract

Powders used in pharmaceuticals require good flowability. The angle of repose and compressibility index are often used to measure the flowability of pharmaceutical powders. However, confirming the relationship between external forces and flowability for smooth powder handling is necessary. Therefore, we measured pharmaceutical excipient powder using a lower cell direct movable constant-volume shear tester and evaluated the powder's physical properties. In this study, we utilized microcrystalline cellulose, widely used as a pharmaceutical excipient and developed in many grades with different physical properties such as particle shape. We measured the shear parameters that describe the characteristic friction and cohesion properties of each microcrystalline cellulose grade. We found that the relative compression ratio (RCR) correlated with the angle of repose. Differences in the shape of the powder yield locus were observed among the grades, and the ratio of the upward convex area of the powder yield locus curve (APC) was defined as the value that quantified these differences. Furthermore, to clarify the relationship between the particle shape parameters (e.g., particle size distribution and shape) and shear parameters, we analyzed these factors using partial least squares regression. RCR was correlated with linearity and was significantly influenced by particle shape. Accurate prediction formulas were also calculated for the stress transmission and relaxation ratios. There was no correlation with the individual shape parameters, and these are considered that is involved in a complex combination. In APC, in addition to the shape parameters used in this study, bulk density had a significant effect.

Keywords: microcrystalline cellulose; partial least square regression; powder yield locus; shear test.