PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Ioana Sovago; Matthias J Gutmann; J Grant Hill; Hans Martin Senn; Lynne H Thomas; Chick C Wilson; Louis J Farrugia Journal: Cryst Growth Des Date: 2014-01-17 Impact factor: 4.076