Interactions of phase equilibria, jet fluid dynamics and mass transfer during supercritical antisolvent micronization: The influence of solvents I. De Marco a , O. Knauer b , F. Cice a , A. Braeuer b,⇑ , E. Reverchon a,⇑ a Department of Industrial Engineering, University of Salerno, Via Ponte Don Melillo 1, 84084 Fisciano, Salerno, Italy b Lehrstuhl für Technische Thermodynamik, Erlangen Graduate School in Advanced Optical Technologies (SAOT), Universität Erlangen-Nürnberg, Paul-Gordan-Straße 6, 91052 Erlangen, Germany highlights " Observation of jet behavior in the supercritical antisolvent process. " Elastic light scattering technique used to visualize different mixing behaviors depending on the kind of solvent. " Interpretation of the difficulty of produce particular morphologies using some solvents. article info Article history: Received 3 April 2012 Received in revised form 19 June 2012 Accepted 29 June 2012 Available online 6 July 2012 Keywords: Supercritical antisolvent process Elastic light scattering Phase behavior Mixing behavior Particle nucleation Micronization abstract 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 characteris- tics 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 dimethyl- sulfoxide 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. Ó 2012 Elsevier B.V. All rights reserved. 1. Introduction Supercritical antisolvent (SAS) precipitation has been success- fully used to micronize many compounds belonging to different categories, such as pharmaceuticals, superconductors, coloring matters, explosives, polymers and biopolymers [1–4]. To describe the SAS process, three aspects and their interactions have to be considered, which are: 1. the fluid dynamics of the injected solution in contact with supercritical carbon dioxide (scCO 2 ); 2. high pressure vapor liquid equilibria (VLEs) of the system formed by solute, solvent and antisolvent; 3. mass transfer to and from the injected solution, that causes the generation of the solute particles. From a fluid dynamic point of view, some authors studied the behavior of the solution injected into pressurized CO 2 [5–8]. Lengs- feld et al. [5] classified the mixing mechanism as ‘‘gas-like’’ when completely miscible conditions were realized in the SAS precipita- tor. This behavior is attributed to the rapid disappearance of the interfacial tension between the injected solution and the bulk CO 2 phase at supercritical conditions. Dukhin et al. [6] introduced two characteristic times and their competition to describe the appearance of one-phase or multi-phase mixing after jet break- up. One is the jet break-up time s jb that quantifies time between 1385-8947/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.cej.2012.06.129 ⇑ Corresponding authors. Fax: +49 9131 85 25851 (A. Braeuer), fax: +39 89 964057 (E. Reverchon). E-mail addresses: andreas.braeuer@aot.uni-erlangen.de (A. Braeuer), ereverchon@ unisa.it (E. Reverchon). Chemical Engineering Journal 203 (2012) 71–80 Contents lists available at SciVerse ScienceDirect Chemical Engineering Journal journal homepage: www.elsevier.com/locate/cej