Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids
Salts of the antiviral drug arbidol (umifenovir) (Arb) with maleate (Mlc) and fumarate (Fum) anions have been obtained, and their crystal structures have been described. The crystal structure of arbidol maleate has been redetermined by single crystal X-ray diffraction at 180K. A new arbidol cocrysta...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2015-12-01
|
| Series: | Crystals |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2073-4352/5/4/650 |
| _version_ | 1818040365722107904 |
|---|---|
| author | Alex N. Manin Artem O. Surov Andrei V. Churakov German L. Perlovich |
| author_facet | Alex N. Manin Artem O. Surov Andrei V. Churakov German L. Perlovich |
| author_sort | Alex N. Manin |
| collection | DOAJ |
| description | Salts of the antiviral drug arbidol (umifenovir) (Arb) with maleate (Mlc) and fumarate (Fum) anions have been obtained, and their crystal structures have been described. The crystal structure of arbidol maleate has been redetermined by single crystal X-ray diffraction at 180K. A new arbidol cocrystal in zwitterion form with succinic acid (Suc) has also been found and characterized. The arbidol zwitterion was not previously seen in any of the drug crystal forms, and the [Arb + Suc] cocrystal seems to be the first found instance. Analysis of the conformational preferences of the arbidol molecule in the crystal structures has shown that it adopts two types of conformations, namely “open” and “closed” ones. Thermal stability of the arbidol salts and cocrystal have been analyzed by means of differential scanning calorimetry, thermogravimetric, and mass-spectrometry analysis. The dissolution study of the arbidol salts and cocrystal performed in aqueous buffer solutions with pH 1.2 and 6.8 has shown that both the salts and the cocrystal dissolve incongruently to form an arbidol hydrochloride monohydrate at pH 1.2 and an arbidol base at pH 6.8, respectively. The cocrystal reaches the highest solubility level in both pH 1.2 and pH 6.8 solutions. |
| first_indexed | 2024-12-10T08:13:22Z |
| format | Article |
| id | doaj.art-5c2da10d3415400bac49eaa2eac07aaf |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-12-10T08:13:22Z |
| publishDate | 2015-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-5c2da10d3415400bac49eaa2eac07aaf2022-12-22T01:56:31ZengMDPI AGCrystals2073-43522015-12-015465066910.3390/cryst5040650cryst5040650Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic AcidsAlex N. Manin0Artem O. Surov1Andrei V. Churakov2German L. Perlovich3Department of Physical Chemistry of Drugs, Institution of Russian Academy of Sciences, G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, Ivanovo 153045, RussiaDepartment of Physical Chemistry of Drugs, Institution of Russian Academy of Sciences, G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, Ivanovo 153045, RussiaDepartment of Crystal Chemistry and X-ray Diffraction Analysis, Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Leninskii Prospekt 31, Moscow 119991, RussiaDepartment of Physical Chemistry of Drugs, Institution of Russian Academy of Sciences, G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, Ivanovo 153045, RussiaSalts of the antiviral drug arbidol (umifenovir) (Arb) with maleate (Mlc) and fumarate (Fum) anions have been obtained, and their crystal structures have been described. The crystal structure of arbidol maleate has been redetermined by single crystal X-ray diffraction at 180K. A new arbidol cocrystal in zwitterion form with succinic acid (Suc) has also been found and characterized. The arbidol zwitterion was not previously seen in any of the drug crystal forms, and the [Arb + Suc] cocrystal seems to be the first found instance. Analysis of the conformational preferences of the arbidol molecule in the crystal structures has shown that it adopts two types of conformations, namely “open” and “closed” ones. Thermal stability of the arbidol salts and cocrystal have been analyzed by means of differential scanning calorimetry, thermogravimetric, and mass-spectrometry analysis. The dissolution study of the arbidol salts and cocrystal performed in aqueous buffer solutions with pH 1.2 and 6.8 has shown that both the salts and the cocrystal dissolve incongruently to form an arbidol hydrochloride monohydrate at pH 1.2 and an arbidol base at pH 6.8, respectively. The cocrystal reaches the highest solubility level in both pH 1.2 and pH 6.8 solutions.http://www.mdpi.com/2073-4352/5/4/650arbidolumifenovirpharmaceutical saltszwitterioncocrystalX-ray diffractionconformation analysisdissolution |
| spellingShingle | Alex N. Manin Artem O. Surov Andrei V. Churakov German L. Perlovich Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids Crystals arbidol umifenovir pharmaceutical salts zwitterion cocrystal X-ray diffraction conformation analysis dissolution |
| title | Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids |
| title_full | Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids |
| title_fullStr | Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids |
| title_full_unstemmed | Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids |
| title_short | Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids |
| title_sort | crystal structures thermal analysis and dissolution behavior of new solid forms of the antiviral drug arbidol with dicarboxylic acids |
| topic | arbidol umifenovir pharmaceutical salts zwitterion cocrystal X-ray diffraction conformation analysis dissolution |
| url | http://www.mdpi.com/2073-4352/5/4/650 |
| work_keys_str_mv | AT alexnmanin crystalstructuresthermalanalysisanddissolutionbehaviorofnewsolidformsoftheantiviraldrugarbidolwithdicarboxylicacids AT artemosurov crystalstructuresthermalanalysisanddissolutionbehaviorofnewsolidformsoftheantiviraldrugarbidolwithdicarboxylicacids AT andreivchurakov crystalstructuresthermalanalysisanddissolutionbehaviorofnewsolidformsoftheantiviraldrugarbidolwithdicarboxylicacids AT germanlperlovich crystalstructuresthermalanalysisanddissolutionbehaviorofnewsolidformsoftheantiviraldrugarbidolwithdicarboxylicacids |