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 CO₂-philic antisolvents and compressed CO₂ suggest that a similar demixing mechanism dominates microparticle formation at these operating conditions.