Separation processes for organic molecules using SCF Technologies.

Supercritical fluids have been applied for many years for the separation of solutes from solids or solute mixtures in both exploratory and industrial applications. In the pharmaceutical industry the generation of pure solid states without impurities is important as the presence of impurities can result in a change in chemical properties or lead to physical instability. The literature on the separation and purification of solutes from solid matrices and solute mixtures using supercritical fluids, with the main emphasis on pharmaceutically important molecules, is reviewed in this article. Also discussed is the application of supercritical fluids in the control of process impurities such as chemical intermediates and residual solvent and in polymorphic control and chiral resolution. As the generation of organic molecules of pharmaceutical interest with high purity is important in pharmaceuticals this review additionally provides a brief overview of highly selective chemical reactions in supercritical fluids.

Crystallization of pure anhydrous polymorphs of carbamazepine by solution enhanced dispersion with supercritical fluids (SEDS).

Pure anhydrous polymorphs of carbamazepine were prepared by solution-enhanced dispersion with supercritical fluids (SEDS). Crystallization of the polymorphs was studied. Mechanisms are proposed that consider the thermodynamics of carbamazepine, supersaturation in the SEDS process, and the binary phase equilibria of organic solvents and the carbon dioxide antisolvent. alpha-Carbamazepine was crystallized at high supersaturations and low temperatures, beta-carbamazepine crystallized from a methanol-carbon dioxide phase split, and gamma-carbamazepine crystallized via nucleation at high temperatures and low supersaturation.

Polymorph control of sulfathiazole in supercritical CO2.

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.

Resolution of ephedrine in supercritical CO(2): A novel technique for the separation of chiral drugs.

Racemic ephedrine has been resolved by diastereomeric salt formation with mandelic acid using supercritical CO(2) as precipitating agent. Crystallizations were performed using the Solution Enhanced Dispersion by Supercritical Fluids (SEDS) technique. Temperature was varied between 35 and 75 degrees C, and pressures ranged from 100 to 350 bar. Resolution, determined by chiral capillary electrophoresis, is described as a function of temperature and density of the supercritical fluid. A comparison of SEDS-produced material with a conventional resolution method shows that SEDS-crystallized material exhibits identical properties to conventionally crystallized material.