Interactions of phase equilibria,jet fluid dynamics and mass transfer during supercritical antisolvent micronization

Supercritical antisolvent (SAS) precipitation has been successfully used in the micronization of several compounds. Nevertheless, the role of high-pressure vapor–liquid equilibria, jet fluid dynamics and mass transfer in determining particle size and morphology is still debated. In this work, CO₂ has been adopted as supercritical antisolvent and elastic light has been used to acquire information on jet fluid dynamics using thin wall injectors for the investigation of the liquid solvents acetone and DMSO at operating conditions of 40 °C in the pressure range between 6 and 16 MPa. The results show that two-phase mixing after jet break-up is the phenomenon that characterizes the jet fluid dynamics at subcritical conditions. When SAS is performed at supercritical conditions a transition between multi-phase and single-phase mixing is observed by increasing the operating pressure. Single-phase mixing is due to the very fast disappearance of the interfacial tension between the liquid solvent and the fluid phase in the precipitator. The transition between these two phenomena depends on the operating pressure, but also on the viscosity and the surface tension of the solvent. Indeed, single-phase mixing has been observed for acetone very near the mixture critical point, whereas DMSO showed a progressive transition for pressures of about 12 MPa.In the second part of the work, a solute was added to DMSO to study the morphology of the microparticles formed during SAS precipitation at the different process conditions, to find a correlation between particle morphology and the observed jet. Expanded microparticles were obtained working at subcritical conditions; whereas spherical microparticles were obtained operating at supercritical conditions up to the pressure where the transition between multi- and single-phase mixing was observed. Nanoparticles were obtained operating far above the mixture critical pressure. The observed particle morphologies have been explained considering the interplay among high-pressure phase equilibria, fluid dynamics and mass transfer during the precipitation process.