Generation of microparticles using CO2 and CO2-philic antisolvents

Precipitation using a compressed antisolvent (PCA) is a demonstrated technology for generation of monodisperse ultrafine particles. Microparticle precipitation using CO2-philic antisolvents was studied with the ultimate goal of developing fundamental approaches to tailor microparticle generation. The ability to micronize small solutes and polymeric systems using CO2-philic liquid antisolvents is compared to precipitation with compressed CO2 and traditional antisolvents. Analogies are made between PCA and CO2-philic antisolvent precipitation based on thermodynamic driving forces and the dynamics of the spray process. Analysis of the interfacial gradient energies of the miscible solvent-antisolvent systems indicates that the spray process is dominated by turbulent mixing and not atomization. The similar microparticle morphologies of amorphous and semicrystalline poly(lactic acid) (PLA) obtained using liquid CO(2)(-)philic antisolvents and compressed CO2 suggest that a similar demixing mechanism dominates microparticle formation at these operating conditions.