The precipitation of CaCO3 via CO2 bubbling using well-defined membranes was used in this study to produce particles of a variety of structures. Studies into the mechanisms of particle formation via this method are limited and are mainly specific to hollow structures. Using a range of analytical techniques, particles produced with a stagnant bubble and in bubbling systems (crossflow and vertical flow) were investigated. The stagnant bubble work concluded that the particles are produced both in bulk but also at the gas/liquid interface which then fall down and collect at the base of the bubble, whereas in a dynamic system the bubble wake has an important role in precipitation of such particles. Precipitation occurs as the solution pH drops due to CO2 bubbling (acidic gas), and these particles are initially comprised of a solid core. As the pH drops further, these particles transform to ones with a hollow core and the pH plays an important role in controlling the particle shell thickness. Allowing the particles to age in solution allows for transformation of such particles from vaterite to calcite. Finally, the particle structure can also be altered by changing the bubbling set up as having a recirculation loop leading to the formation of particles exhibiting a stacked cube.

Particle–particle interactions impact the processability and performance of drug products. Faceted particulates exhibit distinct surface chemistries that affect their adhesion, causing downstream processing challenges such as poor flow, punch sticking, and compaction. Currently, there is a lack of tools to assist formulators in predicting these challenges based on particle properties. Here, we present a methodology for navigating the energy landscape of interparticle interactions. We used molecular mechanics to calculate the interactions between slabs of molecules representing distinct facets. The workflow enables a rapid assessment of the total energy landscape between interacting particles, providing insight into the effects of different surface chemistries and molecular topologies. Previously, the strongest interaction (lowest energy) was used to calculate the propensity to adhere, but we demonstrate that this does not always predict an accurate description of the likely surface interactions. We chose paracetamol to demonstrate the application of this methodology. The most cohesive facets were (101) and (10-1). Comparing surface interactions between particles allows a ranking of the most energetically compatible surfaces. The significance of this ranking and understanding how surface chemistry can impact interparticle interactions is a step toward assisting formulation decisions and improvements in product performance.