Chemical reactor/compounding vessel fingerprinting: scale-up/down considerations for homogeneous and heterogeneous mixing using computational fluid dynamics

Abstract The compounding process is a part of the preparation of a pharmaceutical drug product and is governed by the hydrodynamic characteristics inside the industrial mixing vessel. For the development of a small-scale model of the vessel that would mimic mixing on the industrial-level, these characteristics should be replicated. An appropriate design can be obtained by considering computational fluid dynamics (CFD) calculations, which acknowledge the geometric specifics and fluid behavior in the system. For the appropriate scale-down model design, the mixing process of the fluid inside the industrial compounding vessel was evaluated as well as the movement of the particles that undergo dissolution. The calculated fluid velocities along the streamlines and particle relative velocities along their trajectories provided a description that is specific for a given system. This particular vessel fingerprint can be used for evaluating the suitability of the developed design. Tracer tests were also performed in order to assess the rate of the homogenization process in the large and small scale vessels for the case of a local change of concentration, which occurs upon the addition of substances/excipients. By taking into account the calculated particle slip velocities, the dissolution of particles was modeled by acknowledging the dissolution kinetics and mass transfer. Finally, the designed scale-down mixing vessel was fabricated and tested.