(26b) Impact of Powder Composition on Processing-Relevant Properties of Pharmaceutical Materials: An Experimental Study

In this work, we studied the influence of powder composition on packing density and other processing-relevant properties of binary mixtures, including powder flowability. Binary mixtures of pharmaceutical powders with different particle diameter ratios, α and varying fractions of large and small particles were analyzed systematically. Mixtures of three excipients and one API with different composition (2, 5, 10, 30, 50, 70, 90, 95 and 98 %wt.) were prepared in a Turbula mixer. Powders with different properties and particle size distribution were chosen, in order to obtain three binary mixtures with different size ratios. Then, macroscopic powder properties including bulk (poured) and tapped density (BD and TD) were measured. A powder rheometer was used to measure the flow function coefficient (ffc), cohesion, compressibility and permeability of the binary mixtures. We considered experimentally three classes of binary mixtures, which are characterized by two critical ratios of particle diameter: the critical size ratio of entrance (α_c) and the critical size ratio of replacement (α_r), where α_c = 0.154 and α_r = 0.741. Below the critical size ratio of entrance (α_c), the particle asymmetry (ratio between large and small particle diameters) is high and small particles can fill the voids between larger ones. Below the critical size ratio of replacement (α_r), the particles asymmetry is low and small particles cannot Above α_r, the particles are more or less symmetric in size and overall packing structure does not change by mixing the particles. Our experiments show that there is a non-linear and non-monotonic dependence of all relevant properties on composition for powder mixtures that have an α < α_r. This non-linear behavior is even more significant for strongly asymmetric binary mixtures with α < α_c. We argue that this behavior is related to the composition dependence of random packing of particulate systems. Our results have relevance to pharmaceutical particle processing operations where constant powder mixture properties are needed to ensure quality standards are met; such operations include capsule or die filling during tableting, and the continuous feeding of powders via screw feeders. Our results suggest that for pharmaceutical particle processing operations, where constant powder mixture properties are a prerequisite for process robustness, the diameter ratio of API and excipient particles, a should not be smaller than α_r = 0.741.