Microparticles precipitation using supercritical CO2 as an antisolvent: role of thermal effects and phase equilibria

Abstract

This thesis deals with the micronization of compounds using supercritical fluids. Among the different techniques the supercritical antisolvent (SAS) method was chosen because of the unique properties of materials micronized using supercritical carbon dioxide as an antisolvent. The reasons for this study are twofold: the need for further study of SAS processes in order to correctly design and scale-up them and the need for further development of pharmaceuticals micronizations. Our preliminary study about the role of thermal effects in the SAS precipitation of antibiotics using NMP as solvent has been extended obtaining heat of mixing (excess enthalpy) data for CO2 + organic solvent systems typically used in these micronizations. The interaction between the excess enthalpies and phase equilibria in the SAS precipitation chamber has been elucidated. Pharmaceuticals micronizations using these solvents and CO2 as antisolvent have been carried out and the role of SAS parameters has been analyzed paying special attention to the temperature and pressure conditions, phase equilibria and the heat evolved when the supercritical fluid and the solution are mixed. Two pharmaceuticals have been micronized as pure substances forming micro and nanoparticles and as composite microparticles.