Dry powder blending is a very important industrial and physical process used in the production of numerous pharmaceutical dosage forms such as tablets, capsules, and dry powder aerosols. Key aspects of this unit operation are process monitoring and control. Process control is particularly difficult due to the complexity of particle-particle interactions, which arise from the adhesion/cohesion characteristics of interfaces and morphological characteristics such as particle size, shape, and dispersity. The effects of such characteristics need to be understood in detail in order to correlate individual particle properties to bulk powder properties.

The present dissertation numerically and experimentally quantifies the mixing process to rationalize particle-particle interactions. In particular, near infrared spectroscopy (NIRS) was used to non-invasively characterize in real-time the blending processes and thus investigate the dynamics of blending under different operating conditions. A novel image analysis technique was developed to quantify the scale of segregation from images obtained non-destructively via near infrared chemical imaging (NIR-CI). Although NIR-CI data acquisition times are too long for real-time data collection, NIR-CI has an advantage, in that it provides the spatial distribution of the drug. Therefore, NIRS and NIR-CI are complementary techniques for investigating the complex process of blending dry powders and assessing end-product quality. Additionally, the discrete element method was used to investigate the effect of powder cohesion on the packing fraction. Simulations indicated an exponential relationship between the random loose packing fraction and cohesive forces. Specifically, the packing fraction decreased asymptotically with increased ratio of cohesive force to particle weight. Thus, increasing this force ratio above a critical value has negligible impact on the packing fraction. Such result directly impacts the Hausner ratio flowability measurement, which is directly related to the packing fraction.

Two commonly used tests were compared to assess their utility: the rotational split-cell shear cell test and the Hausner ratio. The Hausner ratio proved to be better suited for characterizing the flowability of unconsolidated powders than the splitring shear cell. Results demonstrate that the optimal flowability test depends on the powder properties and the environment under which flow will be induced.