{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T02:02:04Z","timestamp":1784858524635,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Niclosamide, an anthelmintic drug included in the World Health Organization Model List of Essential Medicines, has recently attracted attention for drug repurposing applications. Its strong tendency to form solvates and hydrates also makes it an attractive candidate for solid-state investigations. This study aimed to evaluate mechanochemical screening as a tool for solvate discovery and to characterize the resulting solid forms. Methods: Mechanochemical screening was performed using twelve selected solvents commonly employed in pharmaceutical research and solid-state investigations and compared with slurry experiments. The obtained phases were characterized by PXRD, DSC, TGA, FTIR, HSM, and SEM. The crystal structure of the new phase was solved from PXRD data and validated by DFT calculations. Stability and kinetic solubility studies were conducted to assess the properties of the identified solid forms. Results: The screening demonstrated the effectiveness of mechanochemistry as a rapid and resource-efficient approach for identifying solvate-forming solvents. Comprehensive characterization clarified the influence of the selected solvents on the solid-state landscape of niclosamide and their relationship with previously reported phases. A new 2-pyrrolidone solvate was discovered and structurally characterized as a triclinic P-1 phase with a 1:1 niclosamide:2-pyrrolidone stoichiometry. The new solvate exhibited distinctive thermal behavior, remained stable for at least 18 months, and showed mechanical robustness under compression. Furthermore, it displayed delayed conversion to niclosamide HA monohydrate in water and enhanced resistance to solid-state transformation under humid conditions. Conclusions: Mechanochemical screening represents an efficient strategy for exploring the solvate landscape of niclosamide. The newly discovered 2-pyrrolidone solvate combines structural stability and favorable solid-state performance, highlighting its potential relevance for future pharmaceutical development.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080906","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:18:51Z","timestamp":1784855931000},"page":"906","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unlocking Niclosamide Solid Forms via Mechanochemistry: Discovery of a 2-Pyrrolidone Solvate"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6541-4883","authenticated-orcid":false,"given":"Ilenia","family":"D\u2019Abbrunzo","sequence":"first","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Rizzetto","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-5804","authenticated-orcid":false,"given":"Lara","family":"Gigli","sequence":"additional","affiliation":[{"name":"Area Science Park Elettra-Sincrotrone Trieste, S.S. 14 Km 163.5 Basovizza, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0288-3233","authenticated-orcid":false,"given":"Nicola","family":"Demitri","sequence":"additional","affiliation":[{"name":"Area Science Park Elettra-Sincrotrone Trieste, S.S. 14 Km 163.5 Basovizza, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4348-9569","authenticated-orcid":false,"given":"Francesca","family":"Argentieri","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3700-7903","authenticated-orcid":false,"given":"Mauro","family":"Stener","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-2700","authenticated-orcid":false,"given":"Nadia","family":"Passerini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, University of Bologna, V. S. Donato 19\/2, 40127 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5766-4014","authenticated-orcid":false,"given":"Beatrice","family":"Perissutti","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.cellsig.2017.04.001","article-title":"Niclosamide: Beyond an Antihelminthic Drug","volume":"41","author":"Chen","year":"2018","journal-title":"Cell. 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