Supercritical CO2‑assisted solvent atomization through a two-fluid nozzle: CFD modeling and experimental characterization of the near-field region

Supercritical CO2 (scCO2)-assisted spray drying can be adapted for continuous drug particle production; however, limited research has been reported on modeling its performance while focusing on the trans-critical operation of the employed nozzles. In this context, we closely explore the behavior of the scCO2-assisted atomization process of methanol, an organic solvent widely employed for spray drying of Active Pharmaceutical Ingredients (APIs). To this end, an Eulerian−Lagrangian Computational Fluid Dynamics (CFD) framework using Ansys FLUENT (2024R2) was developed to describe the scCO2-assisted atomization of methanol through a micro-orifice two-fluid nozzle structure, while thermodynamic submodels were integrated via user-defined functions. Experimental validation and calibration within a set of tested conditions were carried out with the aid of realtime laser-diffraction-based droplet/particle sizing methods. Simulations revealed the formation of methanol microdroplets (2−5 μm) in the near-field, a prerequisite for nanoparticle formation further downstream of the nozzle. Semiempirical correlations applicable for the demonstrated range of conditions were proposed for cost-effective process modeling, and guidelines on best practices were outlined. Experimental characterization of the produced droplets matched predictions with an average error not exceeding 10%. Future work will build on the developed methods to simulate atomization of an scCO2−methanol−API solution to offer a cost-effective optimization tool for relevant drug particle production setups.