Polymorph control of sulfathiazole in supercritical CO2

Sulfathiazole was used to investigate polymorph control in liquid and supercritical CO2. Conventional techniques require a variety of solvents and techniques to produce different polymorphs. The present approach involves precipitation from an organic solution with liquid or supercritical CO2 using the SEDS process.

Sulfathiazole was precipitated from methanol or acetone solutions. Experiments were carried out within a temperature range of 0-120 degrees C. Composition of the fluid phase was varied between x(CO2) = 0.27-0.99. Pressure was constant at 200 bar. Samples obtained were analyzed using SEM, DSC, and XRPD.

Pure polymorphs were obtained at different temperatures and flow rate ratios of CO2/solvent. With methanol Form I, III, and IV and their mixtures could be crystallized. With acetone Form I or a mixture of Form I and amorphous sulfathiazole was obtained. The fluid composition was used as a control parameter to define the process areas (T-x diagram) where the pure forms or mixtures of different forms could be obtained.

The experiments enabled the relationship between flow and temperature for each polymorph to be determined. The crystallization method developed proved to be a simple and efficient technique for reproducible and consistent isolation of sulfathiazole polymorphs.