On the Selection of Limiting Hydrodynamic Conditions for the Supercritical AntiSolvent (SAS) Process

Abstract

The Supercritical AntiSolvent (SAS) technique (which is also referred to as ASES, PCA, or SEDS in the literature) is a promising means of overcoming the low bioavailability found in some active pharmaceutical compounds (APIs). By determining the thermodynamic properties of the phases involved in the process, and applying empirical equations (operations with dimensionless numbers), it has been possible to estimate the different disintegration regimes of the jet when an N-methyl-pyrrolidone (NMP)−ampicillin solution is injected into the CO2-pressurized chamber under pressure (P), temperature (T), and flow rate (QL) conditions in the following ranges: P = 80−180 bar, T = 308−328 K, QL = 1−5 mL/min. The application of the empirical hydrodynamics model highlights the existence of significant mechanisms that stabilize the liquid jet, and it shows that there are limiting hydrodynamic conditions that must be overcome to direct the process toward the formation of uniform spherical nanoparticles and the achievement of higher yields.