Mechanisms controlling supercritical antisolvent precipitate morphology

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 μm range, hollow expanded microparticles with diameters between about 10 and 200 μm, 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.