Solute solubility as criterion for the appearance of amorphous particle precipitation or crystallization in the supercritical antisolvent (SAS) process

Two different supercritical antisolvent (SAS) systems, one precipitating system and one crystallizing system, have been compared in their process behavior in dependence on the solute solubility. The SAS system YAc/DMSO/CO2, which is composed of yttrium acetate (YAc) as solute, dimethylsulfoxide (DMSO) as solvent and carbon dioxide (CO2) as antisolvent, precipitates amorphous particles. The SAS system PCM/EtOH/CO2, which is composed of paracetamol (PCM) as solute, ethanol (EtOH) as solvent and CO2 as antisolvent, crystallizes crystals. Applying in situ elastic and inelastic light scattering it was measured that for the precipitating SAS system YAc/DMSO/CO2 the supersaturation at the location of first particle generation (LFPG) is up to four orders of magnitude larger than for the crystallizing SAS system PCM/EtOH/CO2. This discrepancy correlates with the saturation solubilities of the solutes which found to be approximately four orders of magnitude larger for the crystallizing system than for the precipitating system, investigated by elastic light scattering. Hence, the saturation solubility of the solute in mixtures of solvents and antisolvents could be identified as the indirect classification criterion to distinguish between amorphous precipitating and crystallizing SAS systems. Furthermore, it is shown that for the crystallizing SAS system crystals may be generated from either a supercritical or a liquid phase which is in contrast to the widespread SAS opinion that crystals only can be formed in the liquid phase.