title: Predicting the Solubility of Pharmaceutical Cocrystals in Solvent/Anti-Solvent Mixtures.
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.
authors.affiliation: Department 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.
authors.forename: Linda
authors.initials: L
authors.lastname: Lange
authors.affiliation: Department of Chemical and Biochemical Engineering, Laboratory of Thermodynamics, TU Dortmund University, Emil-Figge-Str. 70, D-44227 Dortmund, Germany. Stefan.Heisel@bci.tu-dortmund.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Heisel
authors.affiliation: Department of Chemical and Biochemical Engineering, Laboratory of Thermodynamics, TU Dortmund University, Emil-Figge-Str. 70, D-44227 Dortmund, Germany. Gabriele.Sadowski@bci.tu-dortmund.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sadowski
mesh_terms: D000097:Acetonitriles / Q000737:chemistry*; D003460:Crystallization; D000431:Ethanol / Q000737:chemistry*; D008958:Models, Molecular; D009536:Niacinamide / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D012997:Solvents; D019802:Succinic Acid / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000097:Acetonitriles; D012997:Solvents; D014867:Water; D009536:Niacinamide; D000431:Ethanol; D019802:Succinic Acid; C032159:acetonitrile
keywords: cocrystal; crystal engineering; phase diagram; solubility; solvent mixtures; thermodynamics