{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T18:27:17Z","timestamp":1783535237800,"version":"3.55.0"},"reference-count":25,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"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>Imiquimod (IMQ) has been successfully formulated to date mainly as semi-solid lipophilic formulations for topical application. In this study, we investigated the solubility of IMQ in solvents suitable for developing innovative formulations in the form of powder obtained, for instance, by spray drying; thus, water, ethanol, methanol, acetone, acetonitrile, and dimethyl sulfoxide were tested at different temperatures. Temperature variations, stirring intensity, and the contact time between IMQ and the solvent greatly affected the evaluation of IMQ equilibrium solubility. The attainment of the solid\u2013liquid equilibrium requires 13 days starting from solid IMQ and 2 days from a cooled-down supersaturated IMQ solution. A correlation between IMQ solubility and the solubility parameters of solvents was not found. IMQ solutions in water, ethanol, methanol, acetonitrile, and dimethyl sulfoxide were neither ideal nor regular. The Scatchard\u2013Hildebrand equation does not apply to IMQ solutions because of association phenomena due to intermolecular hydrogen bonds and\/or \u03c0-stacking, as supported by the hyperchromic effect that was very pronounced in highly polar solvents, such as water, with the increase in temperature. Finally, IMQ solubility values measured in acetone cannot be considered reliable due to the reaction with the solvent, leading to the formation of new molecules.<\/jats:p>","DOI":"10.3390\/pharmaceutics16020282","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T06:00:25Z","timestamp":1708063225000},"page":"282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Imiquimod Solubility in Different Solvents: An Interpretative Approach"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5566-7828","authenticated-orcid":false,"given":"Daisy","family":"Sorgi","sequence":"first","affiliation":[{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9688-6760","authenticated-orcid":false,"given":"Andrea","family":"Sartori","sequence":"additional","affiliation":[{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3758-5164","authenticated-orcid":false,"given":"Saveria","family":"Germani","sequence":"additional","affiliation":[{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosita Nicolella","family":"Gentile","sequence":"additional","affiliation":[{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3160-9586","authenticated-orcid":false,"given":"Annalisa","family":"Bianchera","sequence":"additional","affiliation":[{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3857-7476","authenticated-orcid":false,"given":"Ruggero","family":"Bettini","sequence":"additional","affiliation":[{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"key":"ref_1","first-page":"1300","article-title":"Imiquimod: A Review of off-Label Clinical Applications","volume":"10","author":"David","year":"2011","journal-title":"J. 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