Interactions of phase equilibria, jet fluid dynamics and mass transfer during supercritical antisolvent micronization: The influence of solvents

This work reports the mixing behavior of some organic solvents, used for the supercritical antisolvent technology (SAS), when they are injected into supercritical carbon dioxide. Different mixing characteristics can condition the morphology of the particles produced during the precipitation process. The results, obtained using an elastic light scattering technique, show, that for chloroform and acetone, there is sharp transition from two-phase mixing to single phase jet mixing at pressures larger than the mixture critical pressure of the binary system solvent-carbon dioxide. N-methyl-2-pyrrolidone, ethanol and dimethylsulfoxide show a large transition range between the two-phase mixing regime below the mixture critical pressure and the completely developed one-phase mixing regime above the mixture critical pressure. The transition may cover a pressure range of up to 6 MPa. Mixtures of acetone and dimethylsulfoxide show a mixing behavior that is intermediate between the one of the two pure solvents. The influence of an increase of temperature on the mixing behavior was analyzed for dimethylsulfoxide only; the transition range moved to higher pressures according to the corresponding shift of the mixture critical pressure of the binary system with temperature. A practical indication is, that it is very difficult or even impossible to produce spherical microparticles by SAS, if solvents with a sharp transition between the two-phase and the one-phase mixing regime are used. (C) 2012 Elsevier B.V. All rights reserved.