Dimensionless entropy of fusion as a simple criterion to predict agglomeration in the supercritical antisolvent process

The aim of this work was to understand the agglomeration phenomenon and to predict the agglomeration behavior of materials in the supercritical antisolvent (SAS) process. Carbon dioxide-induced melting point depression is believed to be one of the major causes of the formation of agglomerates during the SAS process. Here, we attempted to observe the CO₂-induced melting behaviors of nine target materials and to recrystallize them in the SAS process. On the basis of the multicomponent Clapeyron equation, which describes the interaction between solute and carbon dioxide, the thermodynamic properties of 32 materials were investigated to correlate melting point depression with the agglomeration phenomenon. In this analysis, the dimensionless entropy of fusion was utilized as a simple criterion to predict agglomeration behavior. The extent of melting point depression was assumed to be inversely proportional to the entropy of fusion of the solute. This assumption enables us to predict the agglomeration behavior of recrystallized pharmaceuticals with dimensionless entropy of fusion during the SAS process. Furthermore, a correlation between the tendency of agglomeration and whether the recrystallized particles have either faceted or nonfaceted form was observed.