Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study

We report on the preparation, characterization, and bioavailability properties of three new crystal forms of ethionamide, an antitubercular agent used in the treatment of drug-resistant tuberculosis. The new adducts were obtained by combining the active pharmaceutical ingredient with three dicarboxy...

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Main Authors:	Simone Bordignon, Paolo Cerreia Vioglio, Elena Amadio, Federica Rossi, Emanuele Priola, Dario Voinovich, Roberto Gobetto, Michele R. Chierotti
Format:	Article
Language:	English
Published:	MDPI AG 2020-08-01
Series:	Pharmaceutics
Subjects:	ethionamide cocrystal solid-state NMR dissolution kryptoracemate salt cocrystal
Online Access:	https://www.mdpi.com/1999-4923/12/9/818

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spelling	doaj-d16fbd5521d241d2936c3cb3052289642020-11-25T03:46:25ZengMDPI AGPharmaceutics1999-49232020-08-011281881810.3390/pharmaceutics12090818Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic StudySimone Bordignon0Paolo Cerreia Vioglio1Elena Amadio2Federica Rossi3Emanuele Priola4Dario Voinovich5Roberto Gobetto6Michele R. Chierotti7Department of Chemistry and NIS Centre, University of Torino, V. Giuria 7, 10125 Torino, ItalyDepartment of Chemistry and NIS Centre, University of Torino, V. Giuria 7, 10125 Torino, ItalyDepartment of Chemistry and NIS Centre, University of Torino, V. Giuria 7, 10125 Torino, ItalyDepartment of Chemistry and NIS Centre, University of Torino, V. Giuria 7, 10125 Torino, ItalyDepartment of Chemistry and NIS Centre, University of Torino, V. Giuria 7, 10125 Torino, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1/via L. Giorgieri 1, 34127 Trieste, ItalyDepartment of Chemistry and NIS Centre, University of Torino, V. Giuria 7, 10125 Torino, ItalyDepartment of Chemistry and NIS Centre, University of Torino, V. Giuria 7, 10125 Torino, ItalyWe report on the preparation, characterization, and bioavailability properties of three new crystal forms of ethionamide, an antitubercular agent used in the treatment of drug-resistant tuberculosis. The new adducts were obtained by combining the active pharmaceutical ingredient with three dicarboxylic acids, namely glutaric, malonic and tartaric acid, in equimolar ratios. Crystal structures were obtained for all three adducts and were compared with two previously reported multicomponent systems of ethionamide with maleic and fumaric acid. The ethionamide-glutaric acid and the ethionamide-malonic acid adducts were thoroughly characterized by means of solid-state NMR (<sup>13</sup>C and <sup>15</sup>N Cross-Polarization Magic Angle Spinning or CPMAS) to confirm the position of the carboxylic proton, and they were found to be a cocrystal and a salt, respectively; they were compared with two previously reported multicomponent systems of ethionamide with maleic and fumaric acid. Ethionamide-tartaric acid was found to be a rare example of kryptoracemic cocrystal. In vitro bioavailability enhancements up to a factor 3 compared to pure ethionamide were assessed for all obtained adducts.https://www.mdpi.com/1999-4923/12/9/818ethionamidecocrystalsolid-state NMRdissolutionkryptoracematesalt cocrystal
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Simone Bordignon Paolo Cerreia Vioglio Elena Amadio Federica Rossi Emanuele Priola Dario Voinovich Roberto Gobetto Michele R. Chierotti
spellingShingle	Simone Bordignon Paolo Cerreia Vioglio Elena Amadio Federica Rossi Emanuele Priola Dario Voinovich Roberto Gobetto Michele R. Chierotti Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study Pharmaceutics ethionamide cocrystal solid-state NMR dissolution kryptoracemate salt cocrystal
author_facet	Simone Bordignon Paolo Cerreia Vioglio Elena Amadio Federica Rossi Emanuele Priola Dario Voinovich Roberto Gobetto Michele R. Chierotti
author_sort	Simone Bordignon
title	Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study
title_short	Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study
title_full	Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study
title_fullStr	Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study
title_full_unstemmed	Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study
title_sort	molecular crystal forms of antitubercular ethionamide with dicarboxylic acids: solid-state properties and a combined structural and spectroscopic study
publisher	MDPI AG
series	Pharmaceutics
issn	1999-4923
publishDate	2020-08-01
description	We report on the preparation, characterization, and bioavailability properties of three new crystal forms of ethionamide, an antitubercular agent used in the treatment of drug-resistant tuberculosis. The new adducts were obtained by combining the active pharmaceutical ingredient with three dicarboxylic acids, namely glutaric, malonic and tartaric acid, in equimolar ratios. Crystal structures were obtained for all three adducts and were compared with two previously reported multicomponent systems of ethionamide with maleic and fumaric acid. The ethionamide-glutaric acid and the ethionamide-malonic acid adducts were thoroughly characterized by means of solid-state NMR (<sup>13</sup>C and <sup>15</sup>N Cross-Polarization Magic Angle Spinning or CPMAS) to confirm the position of the carboxylic proton, and they were found to be a cocrystal and a salt, respectively; they were compared with two previously reported multicomponent systems of ethionamide with maleic and fumaric acid. Ethionamide-tartaric acid was found to be a rare example of kryptoracemic cocrystal. In vitro bioavailability enhancements up to a factor 3 compared to pure ethionamide were assessed for all obtained adducts.
topic	ethionamide cocrystal solid-state NMR dissolution kryptoracemate salt cocrystal
url	https://www.mdpi.com/1999-4923/12/9/818
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Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study

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