Supercritical CO2‑Assisted Solvent Atomization through a Two-Fluid Nozzle: CFD Modeling and Experimental Characterization of the Near-Field Region

Abstract

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 real-time 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.