Model-guided Flow Enhancements of Fine Pharmaceutical Powders Via Dry Particle Coating: Linking Particle-Scale with Bulk-Scale Through Granular Bond Number

Dry coating of fine pharmaceutical powders with nano-sized flow aids has been shown to enhance their bulk properties and processability, greatly facilitating direct compression tablet manufacturing. Here, a model-based understanding of cohesion reduction due to dry coating is presented to provide industrial adoption guidelines. It is shown that, unlike existing single-asperity contact models, our multi-asperity particle contact model explains the effect of the amount of silica, the predominant role of the particle surface roughness, and insufficient flowability enhancements through conventional blending. Our model, coupled with two other models, is used for the determination of the amount and type of guest particles. These models provide an estimate of reduced cohesion as a function of particle size, particle density, asperity size, surface area coverage, and dispersive surface energy. Cohesion is nondimensionalized by using the granular Bond number with the hope of linking the particle scale properties with bulk-scale properties such as flowability, bulk density, and powder agglomeration. Experimental results show that when done properly, dry coating led to significant bulk property enhancements such that 10μm powders attained flowability, fluidizability, and dispersibility as good as 100μm powders; qualitatively agreeing with the model-predicted dramatic reduction in Bond number.