Abramov, Yuriy A. and Loschen, Christoph and Klamt, Andreas (2012) Rational coformer or solvent selection for pharmaceutical cocrystallization or desolvation. JOURNAL OF PHARMACEUTICAL SCIENCES, 101 (10). pp. 3687-3697. ISSN 0022-3549,
Full text not available from this repository. (Request a copy)Abstract
It is demonstrated that the fluid-phase thermodynamics theory conductor-like screening model for real solvents (COSMO-RS) as implemented in the COSMOtherm software can be used for accurate and efficient screening of coformers for active pharmaceutical ingredient (API) cocrystallization. The excess enthalpy, Hex, between an APIcoformer mixture relative to the pure components reflects the tendency of those two compounds to cocrystallize. Thus, predictive calculations may be performed with decent effort on a large set of molecular data in order to identify potentially new cocrystal systems. In addition, it is demonstrated that COSMO-RS theory allows reasonable ranking of coformers for API solubility improvement. As a result, experiments may be focused on those coformers, which have an increased probability of cocrystallization, leading to the largest improvement of the API solubility. In a similar way as potential coformers are identified for cocrystallization, solvents that do not tend to form solvates may be determined based on the highest Hexs with the API. The approach was successfully tested on tyrosine kinase inhibitor axitinib, which has a propensity to form relatively stable solvated structures with the majority of common solvents, as well as on thiophanate-methyl and thiophanate-ethyl benzimidazole fungicides, which form channel solvates. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:36873697, 2012
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PYRIDINE HYDROGEN-BONDS; CO-CRYSTAL; SUPRAMOLECULAR SYNTHONS; PHYSICOCHEMICAL PROPERTIES; QUANTUM-CHEMISTRY; ACID; PREDICTION; MELOXICAM; SOLUBILITY; PROPERTY; cocrystals; solvates; desolvation; crystallization; in silico modeling; crystal engineering; solubility; COSMO-RS; excess enthalpy |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 May 2020 07:15 |
| Last Modified: | 06 May 2020 07:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18053 |
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