Novel Polymorph of Favipiravir—An Antiviral Medication
Various solid forms of pharmaceutically important compounds exhibit different physical properties and bioactivity; thus, knowledge of the structural landscape and prediction of spontaneous polymorph transformations for an active pharmaceutical ingredient is of practical value for the pharmaceutical...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/2/139 |
| _version_ | 1827598893883326464 |
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| author | Alexander S. Goloveshkin Alexander A. Korlyukov Anna V. Vologzhanina |
| author_facet | Alexander S. Goloveshkin Alexander A. Korlyukov Anna V. Vologzhanina |
| author_sort | Alexander S. Goloveshkin |
| collection | DOAJ |
| description | Various solid forms of pharmaceutically important compounds exhibit different physical properties and bioactivity; thus, knowledge of the structural landscape and prediction of spontaneous polymorph transformations for an active pharmaceutical ingredient is of practical value for the pharmaceutical industry. By recrystallization from ethyl acetate, a novel polymorph of 6-fluoro-3-hydroxypyrazine-2-carboxamide (trademark favipiravir, RNA polymerase inhibitor) was obtained and characterized using differential scanning calorimetry (DSC), infra-red spectroscopy and powder X-ray diffraction (XRD) analysis. The favipiravir molecule in two polymorphs realizes similar H-bonding motifs, but the overall H-bonded networks differ. Based on periodic density functional theory calculations, the novel tetragonal polymorph with two interpenetrated H-bonded networks is slightly less stable than the orthorhombic one with the <b>zst</b> topology of the underlying H-bonded net that is in accord with experimentally observed powder XRD patterns of slow conversion of the tetragonal phase to the orthorhombic one. However, topological analysis of net relations revealed that no transformations can be applied to convert H-bonded networks in the experimental unit cells, and DSC data indicate no solid-state reactions at heating. |
| first_indexed | 2024-03-09T04:01:24Z |
| format | Article |
| id | doaj.art-55163b9ec5fe4e5d9d834e3ec1d0e6c3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T04:01:24Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-55163b9ec5fe4e5d9d834e3ec1d0e6c32023-12-03T14:12:10ZengMDPI AGPharmaceutics1999-49232021-01-0113213910.3390/pharmaceutics13020139Novel Polymorph of Favipiravir—An Antiviral MedicationAlexander S. Goloveshkin0Alexander A. Korlyukov1Anna V. Vologzhanina2A. N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, 28 Vavilova str, 119991 Moscow, RussiaA. N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, 28 Vavilova str, 119991 Moscow, RussiaA. N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, 28 Vavilova str, 119991 Moscow, RussiaVarious solid forms of pharmaceutically important compounds exhibit different physical properties and bioactivity; thus, knowledge of the structural landscape and prediction of spontaneous polymorph transformations for an active pharmaceutical ingredient is of practical value for the pharmaceutical industry. By recrystallization from ethyl acetate, a novel polymorph of 6-fluoro-3-hydroxypyrazine-2-carboxamide (trademark favipiravir, RNA polymerase inhibitor) was obtained and characterized using differential scanning calorimetry (DSC), infra-red spectroscopy and powder X-ray diffraction (XRD) analysis. The favipiravir molecule in two polymorphs realizes similar H-bonding motifs, but the overall H-bonded networks differ. Based on periodic density functional theory calculations, the novel tetragonal polymorph with two interpenetrated H-bonded networks is slightly less stable than the orthorhombic one with the <b>zst</b> topology of the underlying H-bonded net that is in accord with experimentally observed powder XRD patterns of slow conversion of the tetragonal phase to the orthorhombic one. However, topological analysis of net relations revealed that no transformations can be applied to convert H-bonded networks in the experimental unit cells, and DSC data indicate no solid-state reactions at heating.https://www.mdpi.com/1999-4923/13/2/139active pharmaceutical ingredientquantum theory “atoms in molecules”polymorphismpowder X-ray diffractionperiodic density functional theory calculations |
| spellingShingle | Alexander S. Goloveshkin Alexander A. Korlyukov Anna V. Vologzhanina Novel Polymorph of Favipiravir—An Antiviral Medication Pharmaceutics active pharmaceutical ingredient quantum theory “atoms in molecules” polymorphism powder X-ray diffraction periodic density functional theory calculations |
| title | Novel Polymorph of Favipiravir—An Antiviral Medication |
| title_full | Novel Polymorph of Favipiravir—An Antiviral Medication |
| title_fullStr | Novel Polymorph of Favipiravir—An Antiviral Medication |
| title_full_unstemmed | Novel Polymorph of Favipiravir—An Antiviral Medication |
| title_short | Novel Polymorph of Favipiravir—An Antiviral Medication |
| title_sort | novel polymorph of favipiravir an antiviral medication |
| topic | active pharmaceutical ingredient quantum theory “atoms in molecules” polymorphism powder X-ray diffraction periodic density functional theory calculations |
| url | https://www.mdpi.com/1999-4923/13/2/139 |
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