(253f) Particle Cohesion Measurement and Simulation for Pharmaceutical Powder Manufacturing

Particle cohesion and adhesion interactions have far-ranging impacts on the manufacturing of particulate solids in the pharmaceutical industry. The ability to measure and model these interactions can aid material selection, improve the design of process equipment, and increase the accuracy of various process simulations and models. To date, research in this area has consisted mainly of adhesion measurements between particles and substrates. While this aids in characterizing the adhesive interaction between powder particles and process equipment surfaces (substrates), it does little to characterize the cohesive interactions between the particles themselves. Colloidal probe microscopy (CPM) using an atomic force microscope (AFM) was used to examine particle-particle cohesion interactions between individual silicon dioxide particles. One particle was immobilized on a silicon substrate, and the other was mounted as a probe on a tipless AFM cantilever. The force of cohesion was measured in various locations across the surface of the substrate-mounted particle. Since CPM measurements detect forces and cantilever deflections normal to the cantilever face, it was hypothesized that the configuration of the particles relative to each other could affect the measured force of cohesion. If the force of interaction is not normal to the cantilever face, the measured force of interaction can be reduced or enhanced as a result of cantilever torsional bending. This effect was observed when the probe particle and substrate-mounted particle interacted in an off-center configuration. When the force of cohesion was predicted using a model that accounted for the effect of particle geometry and cantilever torsion, the predicted values showed good agreement with the measured data. The results confirmed that both the geometry of the particles and torsion of the AFM cantilever can affect the measured cohesion. A protocol for conducting this style of cohesion measurement was developed to minimize these effects. Surface roughness and particle geometry were measured using an AFM and scanning electron microscope, respectively. Based on the observed interaction forces, the new protocol for measuring interparticle interactions, and the roughness and geometry of the interacting particles, the van der Waals force of cohesion between particles was characterized and simulated using a predictive model.