Validation of a new pertinent packing coefficient to estimate flow properties of pharmaceutical powders at a very early development stage, by comparison with mercury intrusion and classical flowability methods

摘要

The present study compares four characterisation techniques, such as packing and rearrangement under pressure methods or shear cell measurement methods, used to evaluate powder flow properties. The reduction of the powder bed volume under low pressures is analysed using mercury porosimetry and two compressibility methods (uniaxial press and volumenometer). Flow functions, deduced from shear cell measurements, are determined using a Johanson Indicizer(TM) Tester. The examination of the reduction of the powder bed volume leads to new parameters such as the packing coefficient (C-t) and the volume of mercury intruded (V-hg). The packing coefficient appears to be a reliable approximation of powder flow properties, whatever cohesive or free flowing : it is actually well correlated with shear cell measurements and it is more accurate than classical flowability tests recommended by the European Pharmacopoeia. Furthermore, this method is easy to use and consumes a small amount of powders (<1 g). All together, this method is able to give-very early in the development-a quite accurate estimation of powder flow properties of new drug substances. This may be very helpful for an early determination of the optimum particle granulometry or for a rapid development of a feasible industrial process. (C) 2001 Kluwer Academic Publishers. [References: 30]