On-line in-situ characterization of CO₂ RESS processes for benzoic acid, cholesterol and aspirin

Rapid expansions of supercritical solutions (RESS) of benzoic acid, cholesterol and aspirin in supercritical CO₂ have been used to investigate the influence of a systematic variation of the pre-expansion temperature and pressure, the distance from the RESS nozzle and the amount of added co-solvent on properties like the average particle diameter D_av and the width of the particle size distribution σ. The properties of the CO₂ expansion have been characterized by a 1-dimensional flow-field model using the Span–Wagner equation of state. Particle detection was performed on-line and in-situ using laser-based three wavelength extinction measurements (3-WEM). For benzoic acid we found a decrease in D_av with increasing pre-expansion pressure, and an increase in D_av with increasing pre-expansion temperature. This is probably due to a lower mass flow rate, which is associated with a lower pre-expansion pressure or higher pre-expansion temperature. This in turn results in a longer residence time in the expansion region and thus a longer particle growth time. Furthermore, a decrease in pre-expansion pressure or an increase in pre-expansion temperature is associated with a decrease in saturation, corresponding to an increase in the critical particle radius and a decrease in the nucleation rate. The size of the benzoic acid particles ranged from about 100 to 500 nm. In addition, we found no obvious correlation between D_av and the distance from the RESS nozzle for benzoic acid and aspirin particles. The particle size was roughly 350 nm and 160 nm for these two solutes, respectively. Obviously, the particle growth processes have already ceased not too far away from the Mach disc. In addition, for cholesterol expansions in CO₂ there was no correlation between the amount and type of co-solvent added. Particle sizes of ∼100 nm were obtained for methanol, ethanol and isopropanol co-solvents. This is most likely due the low solubility of cholesterol in supercritical CO₂, compared with molecules such as benzoic acid, which results in a change of D_av which is too small to be detected using 3-WEM.