Abstract
Non-steroidal anti-inflammatory drugs, such as diclofenac, are gaining attention as repurposed compounds for the treatment of multi-drug resistant tuberculosis. In this study, salts combining diclofenac with clofazimine, are prepared by solvent crystallization and by liquid-assisted grinding. Diclofenac anion possesses an H-bond acceptor which can strongly interact with protic solvent molecules. In this context, selected solvents (protic, aprotic and solvents with increasing molecular volume) are screened in order to investigate solvent impact on crystallization of solvated or unsolvated salt of clofazimine with diclofenac in 1 : 1 ratio. Five solvated salts and one unsolvated salt were successfully crystallized. The ability of the diclofenac anion to interact with a protic molecule is also exploited in order to crystallize a cocrystal of salt with drug : drug ratio different from 1 : 1. Structures of two solvated cocrystal of salts (with acetonitrile and ethylacetate) and two polymorphs of an unsolvated cocrystal of salt combining clofazimine with diclofenac in 1 : 2 ratios are determined.
Original language | English |
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Pages (from-to) | 185-201 |
Number of pages | 17 |
Journal | CrystEngComm |
Volume | 23 |
Issue number | 1 |
Early online date | 17 Nov 2020 |
DOIs | |
Publication status | Published - 7 Jan 2021 |
Funding
This work was performed on XRD and TA equipments from the PC2 platform at the University of Namur. This research used resources of the “Plateforme Technologique de Calcul Intensif (PTCI)” (http://www.ptci.unamur.be) located at the University of Namur, Belgium, which is supported by the FNRS-FRFC, the Walloon Region, and the University of Namur (Conventions No. 2.5020.11, GEQ U.G006.15, 1610468, and RW/GEQ2016). The PTCI is member of the “Consortium des Équipements de Calcul Intensif (CÉCI)” (http://www.cecihpc. be). M. P. thanks the ERASMUS mobility program for the financial support and Prof S. Guccione. L. B. thanks the FRS-FNRS for the funding (research fellow grant). The authors would like to thank Natalia Tumanova for her invaluable advice on editing and formulation of the article.
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Dive into the research topics of 'Taking advantage of solvate formation to modulate drug-drug ratio in clofaziminium diclofenac salts'. Together they form a unique fingerprint.Student theses
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Drug-drug cocrystallization or salt formation as an alternative to combination drugs: A case study on clofazimine
BODART, L. (Author), Wouters, J. (Supervisor), Olivier, Y. (President), Aerts, L. (Jury), Leyssens, T. (Jury), Tumanov, N. (Jury) & APRILE, C. (Jury), 20 Sept 2021Student thesis: Doc types › Doctor of Sciences
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