Laser analyses of mixture formation and the influence of solute on particle precipitation in the SAS process

Laser based Raman and elastic light scattering measurements were performed to study the process of mixture formation and the influence of the solute paracetamol onto the phase behaviour of the pseudo-binary system ethanol/CO2 in the supercritical antisolvent process. From the Raman based technique, mole fraction and partial density distributions of CO2 were obtained. The mole fraction distributions indicate a rapid mixture formation with fast supersaturation of the solute. At the same time, the increase of the CO2 partial density at conditions considerably above the mixture critical point (MCP) indicate a change from a homogeneous supercritical to a multi-phase subcritical flow. This phase change goes along with particle precipitation. Thus, the results of our investigations proof, why past approaches failed to generate amorphous paracetamol nanoparticles with the system paracetamol/ethanol/CO2 above the MCP. Process parameters like injection pressure (20.0–35.0 MPa), chamber pressure of CO2 (7.5–17.5 MPa), temperature (313–333 K) and solute concentration (0–5 wt%) were varied.

Graphical abstractWe report on the process of mixture formation and the influence of the solute paracetamol onto the phase behaviour and the precipitation mechanism of the system paracetamol/ethanol/CO2. So far, amorphous paracetamol nanoparticles never have been produced, since the mixing process appears as a multi-phase mixing process by the addition of the solute paracetamol even at supercritical conditions. An advanced optical setup is used for investigating the different process parameters like injection and chamber pressure, temperature and solute concentration.Figure optionsDownload full-size imageDownload as PowerPoint slide