Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

Manin, Alex N.; Surov, Artem O.; Churakov, Andrei V.; Perlovich, German L.

doi:10.3390/cryst5040650

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Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

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Department 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, Russia

Department of Chemistry, Lomonosov Moscow State University, 1-3 Leninskiye gory, Moscow 119991, Russia

Department 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, Russia

Author to whom correspondence should be addressed.

Academic Editors: Sitaram Velaga and Helmut Cölfen

Crystals 2015, 5(4), 650-669; https://doi.org/10.3390/cryst5040650

Received: 27 October 2015 / Revised: 20 November 2015 / Accepted: 1 December 2015 / Published: 4 December 2015

(This article belongs to the Special Issue Pharmaceutical Cocrystals)

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Abstract

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. View Full-Text

Keywords: arbidol; umifenovir; pharmaceutical salts; zwitterion; cocrystal; X-ray diffraction; conformation analysis; dissolution

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Manin, A.N.; Surov, A.O.; Churakov, A.V.; Perlovich, G.L. Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids. Crystals 2015, 5, 650-669. https://doi.org/10.3390/cryst5040650

AMA Style

Manin AN, Surov AO, Churakov AV, Perlovich GL. Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids. Crystals. 2015; 5(4):650-669. https://doi.org/10.3390/cryst5040650

Chicago/Turabian Style

Manin, Alex N., Artem O. Surov, Andrei V. Churakov, and German L. Perlovich. 2015. "Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids" Crystals 5, no. 4: 650-669. https://doi.org/10.3390/cryst5040650

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Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

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