{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T02:09:25Z","timestamp":1778638165997,"version":"3.51.4"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T00:00:00Z","timestamp":1545177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/DTP\/04567\/2016"],"award-info":[{"award-number":["UID\/DTP\/04567\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/MULTI\/00612\/2013"],"award-info":[{"award-number":["UID\/MULTI\/00612\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The development of effective forms to incorporate poorly soluble drugs into delivery systems remains a problem. Thus, it is important to find alternatives such as finding excipients that increase drug solubility. Ionic liquids (ILs), particularly choline-based ILs, have been studied as solubility enhancers in drug delivery systems. Nonetheless, to acknowledge this property as a functionality, it needs to be proven at non-toxic concentrations. Hence, herein two choline-amino acid ILs were studied as functional excipients by evaluating their influence on the solubility of the poorly water-soluble ferulic acid and rutin, while considering their safety. The solubility of the drugs was always higher in the presence of the ILs than in water. Ionic liquids did not affect the radical scavenging activity of the drugs or the cell viability. Moreover, stable oil-in-water (O\/W) emulsions were prepared containing each drug and the ILs, allowing a significantly higher drug loading. Globally, our results suggest that choline-based ILs may act as green functional excipients, since at non-toxic concentrations they considerably improve drug solubility\/loading, without influencing the antioxidant activity of the drugs, the cell viability, or the stability of the formulations.<\/jats:p>","DOI":"10.3390\/pharmaceutics10040288","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T12:12:44Z","timestamp":1545221564000},"page":"288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Choline-Amino Acid Ionic Liquids as Green Functional Excipients to Enhance Drug Solubility"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5964-2062","authenticated-orcid":false,"given":"Rita","family":"Caparica","sequence":"first","affiliation":[{"name":"CBIOS-Universidade Lus\u00f3fona\u2019s Research Center for Biosciences &amp; Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"},{"name":"Department of Biomedical Sciences, University of Alcal\u00e1, Ctra. Madrid-Barcelona Km. 33.600, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3129-6495","authenticated-orcid":false,"given":"Ana","family":"J\u00falio","sequence":"additional","affiliation":[{"name":"CBIOS-Universidade Lus\u00f3fona\u2019s Research Center for Biosciences &amp; Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"},{"name":"Department of Biomedical Sciences, University of Alcal\u00e1, Ctra. Madrid-Barcelona Km. 33.600, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9197-3024","authenticated-orcid":false,"given":"Andr\u00e9 Rolim","family":"Baby","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, 580 Prof. Lineu Prestes Av., Bl. 15, S\u00e3o Paulo, SP 05508-900, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9876-9015","authenticated-orcid":false,"given":"Maria Eduarda Machado","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"given":"Ana Sofia","family":"Fernandes","sequence":"additional","affiliation":[{"name":"CBIOS-Universidade Lus\u00f3fona\u2019s Research Center for Biosciences &amp; Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5604-6142","authenticated-orcid":false,"given":"Jo\u00e3o Guilherme","family":"Costa","sequence":"additional","affiliation":[{"name":"CBIOS-Universidade Lus\u00f3fona\u2019s Research Center for Biosciences &amp; Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"},{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5150-9910","authenticated-orcid":false,"given":"T\u00e2nia","family":"Santos de Almeida","sequence":"additional","affiliation":[{"name":"CBIOS-Universidade Lus\u00f3fona\u2019s Research Center for Biosciences &amp; Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.drudis.2011.11.007","article-title":"Bridging solubility between drug discovery and development","volume":"17","author":"Di","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, X., Xing, H., Zhao, Y., and Ma, Z. (2018). Pharmaceutical dispersion techniques for dissolution and bioavailability enhancement of poorly water-soluble drugs. 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