Selective production of polymorphs and pseudomorphs using supercritical fluid crystallization from aqueous solutions

A number of supercritical fluid technologies are known to enable the selective production of polymorphs, only by changing the process conditions. These techniques use either supercritical CO₂ or organics as solvent. In this work, the precipitation of small organic molecules from aqueous solution was studied using a mixture of supercritical CO₂ and ethanol as drying medium and as anti-solvent. Glycine, which has three polymorphs, was precipitated by a direct spraying process. By simple manipulation of the flow rates, the process could be tuned to selectively precipitate either pure α- or β-glycine. When increasing the ethanol concentration in the system, the precipitation of the metastable β-glycine was preferred over the precipitation of α-glycine. Small portions of γ-glycine could be found when choosing slow drying conditions. The same process route was applicable to selectively precipitate pseudomorphs as well. Increasing the ethanol concentration in the extractant phase favored the precipitation of phenylalanine anhydrate over the monohydrate form. The study shows that the supercritical fluid crystallization process has significant potential for the selective production of polymorphs and pseudomorphs of water soluble compounds into small particles in a single step.