Investigation of crystallization mechanisms for polymorphic and habit control from the Supercritical AntiSolvent process

Abstract

In this work, the Supercritical AntiSolvent (SAS) process has been used to generate micronized crystals of Sulfathiazole (STZ) from different organic solutions, namely acetone, acetonitrile, tetrahydrofuran and acetic acid. The flow rates of CO2 (2–21gmin−1) and of the organic solution (0.19–6mLmin−1), as well as STZ concentration in the organic solution (20–70% under the saturation), have been varied to identify the conditions leading to powders exhibiting only one polymorphic form. Pressure (10MPa) and temperature (313K) have been kept constant. In this paper, thermodynamic and hydrodynamic aspects are discussed so as to rationalize the obtained crystal characteristics and provide a new way to control the SAS process applied to drug pre-formulation. The influence of the organic solvent nature on both the polymorphic form and the habit of generated crystals, has been particularly discussed.