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

• Published in: The Journal of supercritical fluids Vol. 50; no. 3; pp. 265 - 275
• Main Authors: Dowy, S., Braeuer, A., Reinhold-López, K., Leipertz, A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-10-2009
• Subjects: Elastic light scattering; Ethanol; Mixing behaviour; Paracetamol; Particle nucleation; Phase behaviour; Raman scattering; SAS; Supercritical antisolvent process; Supercritical antisolvent process; Particle nucleation; Paracetamol; Mixing behaviour; SAS; Ethanol; Raman scattering; Elastic light scattering; Phase behaviour
• ISSN: 0896-8446; 1872-8162
• DOI: 10.1016/j.supflu.2009.06.018

We 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/CO
2. 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.
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/CO
2 in the supercritical antisolvent process. From the Raman based technique, mole fraction and partial density distributions of CO
2 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 CO
2 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/CO
2 above the MCP. Process parameters like injection pressure (20.0–35.0
MPa), chamber pressure of CO
2 (7.5–17.5
MPa), temperature (313–333
K) and solute concentration (0–5
wt%) were varied.