{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T16:05:35Z","timestamp":1774627535602,"version":"3.50.1"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Febuxostat (FEB) is a poorly soluble xanthine oxidase inhibitor, which limits its in vitro dissolution performance. This study aimed to enhance the aqueous solubility and dissolution behavior of FEB through crystal engineering (salt and co-crystal formation) and the development of PEG6000-based amorphous solid dispersions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three FEB salts with p-toluenesulfonic acid (Tos1), tromethamine, and N-methyl-D-glucamine, as well as one FEB co-crystal with acridine (Acd1), were prepared together with their amorphous solid dispersions using PEG6000. Solubility, dissolution, and physical stability were evaluated in water and biorelevant media (FaSSIF). Cytotoxicity was assessed in HepG2 cells, while antioxidant and anti-inflammatory activities were investigated in monosodium urate\u2013stimulated macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>Salt formation significantly improved FEB solubility, with Tos1 increasing solubility from 27\u2009\u00b1\u20092\u00a0\u03bcg\/ml (FEB) to 100\u2009\u00b1\u20092\u00a0\u03bcg\/ml in water and from 316\u2009\u00b1\u20092\u00a0\u03bcg\/ml to 364\u2009\u00b1\u20092\u00a0\u03bcg\/ml in FaSSIF. Incorporation into PEG6000 further enhanced Tos1 solubility to 134\u2009\u00b1\u20092\u00a0\u03bcg\/ml in water and 481\u2009\u00b1\u20092\u00a0\u03bcg\/ml in FaSSIF. In contrast, the Acd1 co-crystal showed limited solubility in water but exhibited slower dissolution, suggesting suitability for sustained-release applications. None of the novel formulations increased cytotoxicity. Tos1 and its PEG6000 dispersion maintained the highest HepG2 cell viability and significantly reduced malondialdehyde levels and intracellular uric acid in macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The combined application of crystal engineering and PEG6000-based amorphous solid dispersions selectively enhances the solubility, dissolution, and in vitro biological performance of febuxostat. This strategy offers a rational approach for optimizing FEB formulations and addressing the limitations associated with poorly soluble drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgag019","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T15:07:28Z","timestamp":1774624048000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrating crystal engineering with PEG6000 conjugation to formulate advanced solid dispersions of febuxostat for gout management"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9101-6571","authenticated-orcid":false,"given":"Doriana T","family":"Ungur","sequence":"first","affiliation":[{"name":"Faculty of Biology and Geology, Doctoral School in Integrative Biology, Babe\u015f-Bolyai University , 5-7 Clinicilor Street, Cluj-Napoca 400006 ,","place":["Romania"]},{"name":"TeraCrystal SRL , 67-103 Donat Street, Cluj-Napoca 400293 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