Chemical Engineering Journal 169 (2011) 358–370 Contents lists available at ScienceDirect Chemical Engineering Journal journal homepage: www.elsevier.com/locate/cej Mechanisms controlling supercritical antisolvent precipitate morphology Ernesto Reverchon a,b,∗ , Iolanda De Marco a a Department of Industrial Engineering (Chemical Engineering Section), University of Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy b NANO MATES, Research Centre for Nanomaterials and Nanotechnology, University of Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy article info Article history: Received 22 October 2010 Received in revised form 9 February 2011 Accepted 25 February 2011 Keywords: Supercritical antisolvent process Mixing behavior Jet break-up Particle formation mechanisms abstract Supercritical antisolvent precipitation (SAS) has been successfully used to micronize several kinds of materials. A great variety of morphologies, such as nanoparticles with mean diameters in the 30–200 nm range, spherical microparticles in the 0.25–20 m range, hollow expanded microparticles with diameters between about 10 and 200 m, and crystals with various habits and micrometric dimensions have been frequently obtained. However, a comprehensive analysis of the mechanisms that control the attainment of the different particle size and morphologies has not been proposed, yet. In this work, the interactions among high-pressure vapor–liquid equilibria, surface tension variations, jet fluid dynamics, mass transfer, nucleation and growth are indicated as the responsible for the observed SAS morphologies. The possible particle formation mechanisms are indicated and discussed on the basis of the experimental results. Liquid jet break-up and surface tension vanishing at supercritical conditions are indicated as the processes in competition to produce spherical microparticles or nanoparticles. Two possible mechanisms can be involved in crystals formation: (1) droplets drying followed by a fast crystallization kinetics, that can led to the formation of crystals with a spherical predominant shape; (2) the precipitation from an expanded liquid phase that can led to crystals with various habits and dimensions, depending on the interactions with the liquid solvent used. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Supercritical carbon dioxide (SC-CO 2 ) based techniques, like rapid expansion of supercritical solutions (RESS), supercritical assisted atomization (SAA) and supercritical antisolvent techniques (GAS and SAS) have been extensively used to micronize compounds belonging to several categories [1–4]. However, the most used pro- cess is the supercritical antisolvent (SAS) precipitation, that has been successfully used to process pharmaceuticals, superconduc- tors, colouring matters, explosives, polymers and biopolymers, as indicated in some reviews [5,6]. Several particle morphologies have been recurrently obtained by SAS: nanoparticles with mean diameters in the 30–200 nm range, microparticles in the 0.25–20 m range, expanded hollow microparticles (sometimes defined as balloons) with diameters between about 10 and 200 m and crystals with micrometric dimensions and various habits [1,2,5]. The effect of the SAS operating parameters, such as pressure, temperature, concentration in the liquid solution and carbon diox- ide molar fraction, on particle size (PS) and particle size distribution (PSD) was studied by several authors [7–15]. But, until now, only ∗ Corresponding author. Fax: +39 89 964057. E-mail address: ereverchon@unisa.it (E. Reverchon). some papers discussed about the precipitation mechanisms, the interactions of fluid dynamics, surface tension variations, mass transfer, vapor liquid equilibria (VLEs), nucleation and growth mechanisms involved in this process [13,16–23]. An interpretation of the SAS process taking into account gas mixing was proposed by Lengsfeld et al. [24], that studied the liquid surface tension evolution and disappearance, in jets of immiscible, partially miscible and miscible fluids injected into sub- critical or supercritical antisolvent. They determined whether the jets atomize into droplets or evolve as a gaseous plume. In the case of miscible fluids (liquid and CO 2 mixture above the mix- ture critical point), they observed that liquid droplets never form, because the surface tension vanishes before that the jet break-up occurs. Successively, Sarkari et al. [13], Dukhin et al. [25], Badens et al. [26], Gokhale et al. [27], and Obrzut et al. [28] studied the jet atomization in pressurized gases, observing that turbulent single-phase mixing dominates at completely developed supercrit- ical conditions. It was also observed that the transition between multi-phase (formation of droplets after jet break-up) and single- phase mixing (no formation of droplets) takes place at pressures slightly above the mixture critical pressure (MCP). Due to the non-equilibrium conditions during mixing, a dynamic (transient) interfacial tension exists that decreases and disappears in the time lag between the inlet of the liquid and its transformation in a gas mixture. 1385-8947/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.cej.2011.02.064