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Flow Function of Pharmaceutical Powders at Low-Stress Conditions Can Be Inferred Using a Simple Flow-Through-Orifice
Xingcheng Zhou1, Ewa Nauka1, Ajit Narang1
1Small Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, California 94080.
Abstract:
Multiple pharmaceutical powder processes operate at stresses lower than utilized in typical lab-scale shear cell testing. To bridge this gap, we developed a method to determine intrinsic powder flow properties, in particular, flow function (FFc), under such low stresses. A simple, commercially-available flow-through-orifice device (Flodex™ apparatus) was selected. By developing a theoretical framework using Jenike's radial stress field analysis, the major principal stress and FFc of the tested powder can be derived from the otherwise empirical "Flodex" experiment. This method was applied to 10 distinct pharmaceutical powders. The major principal stresses associated with the test were estimated to be in the order of 100 Pa, significantly lower than what is achievable using shear cell-based methods. The resulting FFc values are generally consistent with the data extrapolated from ring shear testing. We showed that for pharmaceutical powders, FFc decreases with decreasing consolidation stress, but the values are always greater than 1. Therefore, the threshold for poor/acceptable flowability (by FFc) should be used with caution at low-stress conditions. Through this work, we showed that by integrating the radial stress field theory with a simple flow-through-orifice experiment, intrinsic powder flow properties under low stresses could be reliably determined.
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