Supercritical Fluid Processing for Nanoparticle Fabrication

Supercritical fluid processing harnesses the unique properties of fluids at temperatures and pressures above their critical points to produce nanoparticles with precise control over size, morphology and composition. Among available media, supercritical carbon dioxide (scCO₂) is most widely used owing to its tunable density, low toxicity and facile removal. Key techniques include rapid expansion of supercritical solutions (RESS), where a solute-laden supercritical solution is depressurised to precipitate fine particles, and the supercritical antisolvent (SAS) method, in which scCO₂ extracts solvent from a solute solution to induce nanoparticle formation. These processes enable narrow size distributions, minimal solvent residues and adjustable surface characteristics, making them highly attractive for pharmaceuticals, catalysts and advanced materials. Recent advances have focused on integrating inline monitoring, computational fluid dynamics and multivariate process optimisation to ensure reproducibility at scale. Applications span drug delivery systems with enhanced bioavailability, polymeric carriers for controlled release and functional metal or metal-oxide nanostructures for sensing and energy storage. The global significance lies in reduced environmental footprint, streamlined downstream processing and consistent product quality, supporting regulatory demands for green and continuous manufacturing.

Research from Nature Portfolio

Recent studies have reported the solubility of pantoprazole sodium sesquihydrate in scCO₂ across a range of temperatures (308–338 K) and pressures (12–27 MPa), demonstrating that refined thermodynamic models can predict nanoparticle yield and guide process design for acid-labile APIs. Another investigation explored the solubility of ketoconazole in both binary scCO₂ systems and ternary mixtures with menthol cosolvent, revealing that small amounts of cosolvent dramatically enhance drug loading and permit finer control over particle size. A separate work assessed decitabine solubility under supercritical conditions using gravimetric techniques and various semi-empirical correlations, highlighting a crossover pressure effect on temperature-dependent solubility and underpinning a Quality-by-Design framework for continuous oral dosage manufacture.

Supercritical Fluid Processing for Nanoparticle Fabrication publication trend

The graph below shows the total number of articles in supercritical fluid processing for nanoparticle fabrication across all publications each year (not limited to Nature Index journals).

Technical terms

Supercritical fluid: A substance at temperature and pressure above its critical point, exhibiting combined liquid-like density and gas-like diffusivity, used to manipulate solute solubility and precipitation.

Supercritical carbon dioxide (scCO₂): Carbon dioxide maintained above 31.1 °C and 7.38 MPa, valued for its inertness, low critical conditions and easy removal from products.

Rapid expansion of supercritical solutions (RESS): A nanoparticle formation method where a solute is dissolved in a supercritical fluid and then rapidly depressurised to precipitate particles.

Supercritical antisolvent (SAS): A technique in which scCO₂ acts as an antisolvent to extract liquid solvent from a solute solution, inducing controlled nucleation and growth of nanoparticles.

Cosolvent: A secondary solvent added to a supercritical fluid to enhance the solubility of polar or high-molecular-weight solutes and adjust particle morphology.

References

1. Solubility measurement and thermodynamic modeling of pantoprazole sodium sesquihydrate in supercritical carbon dioxide. Scientific Reports (2022).
2. Solubility of Ketoconazole (antifungal drug) in SC-CO2 for binary and ternary systems: measurements and empirical correlations. Scientific Reports (2021).
3. Experimental and thermodynamic modeling decitabine anti cancer drug solubility in supercritical carbon dioxide. Scientific Reports (2021).
4. Measurement and modeling of dapagliflozin propanediol monohydrate (an anti-diabetes medicine) solubility in supercritical CO2: Evaluation of new model. Journal of CO2 Utilization (2024).
5. Experimental measurement and thermodynamic modeling of Chlorothiazide solubility in supercritical carbon dioxide. Case Studies in Thermal Engineering (2023).
6. Nanoparticles and Nanocrystals by Supercritical CO2-Assisted Techniques for Pharmaceutical Applications: A Review. Applied Sciences (2021).