{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:31:32Z","timestamp":1760059892304,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nepafenac is an anti-inflammatory drug used in ophthalmology, marketed as a suspension due to its low aqueous solubility. A solution formulation could provide better bioavailability than suspension and facilitate single unit doses, avoiding the use of preservatives which are required to maintain sterility in multidose packaging. In this study, solubilization of nepafenac was achieved in the presence of randomly methylated \u03b2-cyclodextrin (RAMEB) and the actual complexation was assessed by NMR and phase-solubility studies. It was also found that the addition of hydrophilic polymers plays an important role in allowing increased solubilization of nepafenac at the same cyclodextrin concentration. Compared to complexes of nepafenac with other cyclodextrins, only 5% RAMEB was sufficient to solubilize 0.3% (w\/v) nepafenac, enabling for the first time the development of an ophthalmic solution that proved chemically and physically stable for 12 months at 25 \u00b0C. The formulated solutions of nepafenac were tested for cytotoxicity on human corneal epithelial cells (HCE-2) and the results suggest their potential as a valuable and safe alternative to the commercially available 0.3% (w\/v) suspension of the drug.<\/jats:p>","DOI":"10.3390\/molecules30153090","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T14:22:44Z","timestamp":1753280564000},"page":"3090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergic Effect of Methyl-\u03b2-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic Solution"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0669-9387","authenticated-orcid":false,"given":"Maria Grazia","family":"Saita","sequence":"first","affiliation":[{"name":"MEDIVIS, Via Carnazza 34 C, 95030 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3971-0315","authenticated-orcid":false,"given":"Fabiola","family":"Spitaleri","sequence":"additional","affiliation":[{"name":"MEDIVIS, Via Carnazza 34 C, 95030 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Mangano","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danilo","family":"Aleo","sequence":"additional","affiliation":[{"name":"MEDIVIS, Via Carnazza 34 C, 95030 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7564-0692","authenticated-orcid":false,"given":"Angela","family":"Patti","sequence":"additional","affiliation":[{"name":"CNR\u2014Institute of Biomolecular Chemistry, Via Paolo Gaifami 18, 95126 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1023\/A:1007049015148","article-title":"Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. assessment of anti-inflammatory efficacy","volume":"24","author":"Gamache","year":"2000","journal-title":"Inflammation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.jcrs.2007.05.015","article-title":"In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac","volume":"33","author":"Walters","year":"2007","journal-title":"J. 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