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Predicting the Solubility of Pharmaceutical Cocrystals in Solvent/Anti-Solvent Mixtures
Linda Lange1, Stefan Heisel2, Gabriele Sadowski3
1Department of Chemical and Biochemical Engineering, Laboratory of Thermodynamics, TU Dortmund University, Emil-Figge-Str. 70, D-44227 Dortmund, Germany. Linda.Lange@bci.tu-dortmund.de.
Abstract:
In this work, the solubilities of pharmaceutical cocrystals in solvent/anti-solvent systems were predicted using PC-SAFT in order to increase the efficiency of cocrystal formation processes. Modeling results and experimental data were compared for the cocrystal system nicotinamide/succinic acid (2:1) in the solvent/anti-solvent mixtures ethanol/water, ethanol/acetonitrile and ethanol/ethyl acetate at 298.15 K and in the ethanol/ethyl acetate mixture also at 310.15 K. The solubility of the investigated cocrystal slightly increased when adding small amounts of anti-solvent to the solvent, but drastically decreased for high anti-solvent amounts. Furthermore, the solubilities of nicotinamide, succinic acid and the cocrystal in the considered solvent/anti-solvent mixtures showed strong deviations from ideal-solution behavior. However, by accounting for the thermodynamic non-ideality of the components, PC-SAFT is able to predict the solubilities in all above-mentioned solvent/anti-solvent systems in good agreement with the experimental data.
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