Measurements of the phase behavior of ternary systems of interest to the GAS process: II. The system CO2 + methanol + prednisolone

In this work, the phase behavior of the ternary system carbon dioxide + methanol + prednisolone has been studied experimentally. For this purpose, carbon dioxide has been chosen as the anti-solvent gas, methanol as the organic solvent, and prednisolone as the model drug that should be micronized using the GAS process. In each experiment, a solution of prednisolone in methanol was expanded using carbon dioxide as the anti-solvent. A synthetic method was used for measuring bubble point curves, and the solid (prednisolone)–liquid boundaries. Three-phase equilibrium data of solid (prednisolone)–liquid–vapor were obtained from the intersection of the two-phase isopleths vapor–liquid and solid–liquid. Results are reported for this ternary system at carbon dioxide concentrations ranging from 13.1 to 48.4 mol%, and within temperature and pressure ranges of 293.1–367.0 K and 2.4–9.9 MPa, respectively.In one of the mixtures it was observed that the concentration of carbon dioxide has a great effect on the phase behavior of the solution: at lower concentrations, carbon dioxide has a co-solvency effect, therefore, increasing the carbon dioxide concentration decreases the precipitation temperature. However, at higher concentrations, carbon dioxide acts as an anti-solvent, thus precipitation temperature increases with increasing carbon dioxide concentration. Also, it is shown that at a proper temperature, it is possible to precipitate most of the dissolved solute with small changes in pressure.

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► Carbon dioxide has a great effect on the phase behavior of the studied solution.
► At lower concentrations, carbon dioxide has a co-solvency effect.
► At higher concentrations, carbon dioxide acts as an anti-solvent.
► It is shown that at a proper temperature, it is possible to precipitate most of the dissolved solute with small changes in pressure.