Novel multicomponent crystal forms of artesunate

Madu, Shadrack J., Wang, Ke, Fábián, László and Li, Mingzhong (2025) Novel multicomponent crystal forms of artesunate. CrystEngComm. ISSN 1466-8033

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Abstract

Artesunate (ATS), a BCS class II drug widely used for anti-malaria therapy, exhibits not only poor solubility but also poor stability. This study aimed to discover novel multicomponent crystal forms of ATS with improved physicochemical properties. Screening of 117 coformer candidates using mechanochemical solvent drop grinding (SDG) or solvent evaporation (SE) resulted in discovering five novel multicomponent crystal forms of ATS with 4-aminobenzoic acid (ABA), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,2-di(pyridine-4-yl)ethane (DPE), 1,10-phenanthroline (PHEN) and urea (URE). Based on the ΔpKa rule, FTIR results and structure analyses, these solids are cocrystals except DABCO. Additionally, ATS–URE cocrystals can be crystallised as different solvate forms, including methanol, ethanol, and acetonitrile. Interestingly two crystal forms of 2 : 1 ATS–DABCO have been discovered, i.e., form 1 is cocrystal and form 2 is salt. The crystal structures of these multicomponent ATS crystals were determined by single crystal X-ray diffraction and characterised by powder X-ray diffraction, Fourier transform infrared spectroscopy and different thermal analytical techniques (i.e., differential scanning calorimetry, thermogravimetric analysis and hot stage microscopy). It has been shown that some of the multicomponent ATS crystals can significantly improve the in vitro dissolution performance of ATS and its stability in solution. Unfortunately, the solid-state stability study shows that these multicomponent crystals do not exhibit better stability than the raw ATS under the conditions studied. In conclusion, the discovery of more multicomponent crystals of ATS with improved physiochemical properties (e.g., solubility and/or stability) could help to enhance its therapeutic efficacy.

Item Type:	Article
Additional Information:	Data availability: Data supporting this article have been included as part of the Supporting Materials. Crystal structures have been deposited in the Cambridge Structural Database (CSD) with CCDC deposition numbers 2427253 – 2427258.
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
UEA Research Groups:	Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
Depositing User:	LivePure Connector
Date Deposited:	29 Oct 2025 16:31
Last Modified:	03 Nov 2025 00:59
URI:	https://ueaeprints.uea.ac.uk/id/eprint/100846
DOI:	10.1039/D5CE00279F

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