Loschen, Christoph and Klamt, Andreas (2018) Cocrystal Ternary Phase Diagrams from Density Functional Theory and Solvation Thermodynamics. CRYSTAL GROWTH & DESIGN, 18 (9). pp. 5600-5608. ISSN 1528-7483, 1528-7505
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Several solid-liquid ternary phase diagrams consisting of an active ingredient, an excipient (coformer), and a solvent have been computed by means of density functional theory and COSMO-RS solvation thermodynamics. In all these ternary systems, cocrystal formation occurs; furthermore, the active ingredient and coformer are capable of forming strong, concerted hydrogen bonds in solution. The formation of such exceptionally strong bonds in solution has been taken into account by the introduction of an additional binary interaction parameter. This approach leads to a good agreement with experimental data using a minimum set of fit parameters. Quantum-chemically computed interaction enthalpies between solutes are of similar magnitude as the optimized interaction parameters and computed free energies in solution corroborate the existence of a significant population of aggregated drug-coformer complexes. The outlined procedure provides detailed insights into solvation and solubility enhancement effects at the molecular level. Those findings may be of use for example for solvent screening applications for ternary systems in order to support pharmaceutical process development work.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COSMO-RS; SOLVENT SELECTION; SOLUBILITY; POLYMORPHS; ENERGY; APPROXIMATION; COMPLEXATION; EQUILIBRIUM; PREDICTION; STABILITY; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Jan 2020 15:38 |
| Last Modified: | 08 Jan 2020 15:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13904 |
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