{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:18:07Z","timestamp":1790252287735,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union Recovery and Resilience Facility and the budget of the Republic of Latvia","award":["RSU-ZG-2024\/1-0033"],"award-info":[{"award-number":["RSU-ZG-2024\/1-0033"]}]},{"name":"European Union Recovery and Resilience Facility and the budget of the Republic of Latvia","award":["5.2.1.1.i.0\/2\/24\/I\/CFLA\/005"],"award-info":[{"award-number":["5.2.1.1.i.0\/2\/24\/I\/CFLA\/005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Eutectic solvents have become a viable choice to create innovative pharmaceutical technologies within the framework of the green chemistry approach. Despite the growing applicative interest, a general gap remains in the pharmaceutical sector regarding thorough and systematic research of their properties and useful applications. In this work, eutectic solvents have been prepared from choline chloride and polyols (sorbitol, xylitol, mannitol, and isomalt) at different molar ratios (1:1, 2:3, and 3:2), characterised, and used for the solubility enhancement of poorly water-soluble drugs (ibuprofen and naproxen) as well as the potential drug candidate apigenin. The interactions between the eutectic solvent components were investigated by DSC, FTIR, and refractive index methods. In all eutectic solvents, the water content detected by Karl Fischer titration and loss on drying was less than 3%. Solubility studies, carried out using the shake-flask method, showed significant solubility enhancement of the following: ibuprofen: ~152-fold increase, naproxen: ~144-fold increase, and apigenin: ~188-fold increase. These findings highlighted the great potential of eutectic solvents as solubility enhancers in the development of novel and more effective drug delivery systems.<\/jats:p>","DOI":"10.3390\/ijms27073110","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:22:36Z","timestamp":1774858956000},"page":"3110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Green Innovative Approach for Solubility Enhancement of Poorly Water-Soluble Drugs Using Choline Chloride\u2013Polyol Eutectic Solvents"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0169-3027","authenticated-orcid":false,"given":"Liga","family":"Petersone","sequence":"first","affiliation":[{"name":"Leading Research Group, Faculty of Pharmacy, R\u012bga Stradi\u0146\u0161 University, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4307-4198","authenticated-orcid":false,"given":"Rihards","family":"Mahinovs","sequence":"additional","affiliation":[{"name":"Leading Research Group, Faculty of Pharmacy, R\u012bga Stradi\u0146\u0161 University, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9413-2355","authenticated-orcid":false,"given":"Zolt\u00e1n M\u00e1rk","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Leading Research Group, Faculty of Pharmacy, R\u012bga Stradi\u0146\u0161 University, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8771-3470","authenticated-orcid":false,"given":"Valentyn","family":"Mohylyuk","sequence":"additional","affiliation":[{"name":"Leading Research Group, Faculty of Pharmacy, R\u012bga Stradi\u0146\u0161 University, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"144850","DOI":"10.1016\/j.jclepro.2025.144850","article-title":"Seventy-two shades of environmental sustainability in healthcare: A holistic framework proposal","volume":"493","author":"Asperti","year":"2025","journal-title":"J. Clean. Prod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1002\/bse.4077","article-title":"Greening the Pharmaceutical Supply Chain","volume":"34","author":"Belal","year":"2024","journal-title":"Bus. Strategy Environ."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jeli\u0144ski, T., Przyby\u0142ek, M., Mianowana, M., Misiak, K., and Cysewski, P. (2024). Deep Eutectic Solvents as Agents for Improving the Solubility of Edaravone: Experimental and Theoretical Considerations. Molecules, 29.","DOI":"10.3390\/molecules29061261"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155011","DOI":"10.1016\/j.cej.2024.155011","article-title":"Hydrophobic deep eutectic solvents as novel media for the recycling of waste photovoltaic modules","volume":"498","author":"Yang","year":"2024","journal-title":"Chem. Eng. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.molliq.2015.01.052","article-title":"Solubility of naproxen in 2-propanol + water mixtures at various temperatures","volume":"206","author":"Mohammadzade","year":"2015","journal-title":"J. Mol. Liq."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1039\/D5PM00171D","article-title":"Eutectic formulations in pharmaceutical development: A comprehensive review of modulation strategies","volume":"2","author":"Sultana","year":"2025","journal-title":"RSC Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kumari, L., Choudhari, Y., Patel, P., Gupta, G.D., Singh, D., Rosenholm, J.M., Bansal, K.K., and Kurmi, B.D. (2023). Advancement in Solubilization Approaches: A Step towards Bioavailability Enhancement of Poorly Soluble Drugs. Life, 13.","DOI":"10.3390\/life13051099"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, J., Li, M., Duan, L., Lin, Y., Cui, X., Yang, Y., and Wang, C. (2022). Deep Eutectic Systems as Novel Vehicles for Assisting Drug Transdermal Delivery. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14112265"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e29783","DOI":"10.1016\/j.heliyon.2024.e29783","article-title":"Pharmaceutical applications of therapeutic deep eutectic systems (THEDES) in maximising drug delivery","volume":"10","author":"Javed","year":"2024","journal-title":"Heliyon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1080\/03639040802587799","article-title":"Polyols as filler-binders for disintegrating tablets prepared by direct compaction","volume":"35","author":"Bolhuis","year":"2009","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Poka, M.S., Milne, M., Wessels, A., and Aucamp, M. (2023). Sugars and Polyols of Natural Origin as Carriers for Solubility and Dissolution Enhancement. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15112557"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"226","DOI":"10.36961\/si14095","article-title":"Polyols\u2014More than sweeteners","volume":"138","author":"Radeloff","year":"2013","journal-title":"Zuckerind. Sugar Ind."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Horv\u00e1th, Z.M., Kukuls, K., Frolova, A.J., \u017dogota, M., Buczkowska, E.M., P\u0113tersone, L., and Mohylyuk, V. (2025). Effervescent Tablet Preparation by Twin-Screw Melt Granulation with Sorbitol as a Melt Binder. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17050676"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"119742","DOI":"10.1016\/j.molliq.2022.119742","article-title":"Hydrogen bonds in aqueous choline chloride solutions by DFT calculations and X-ray scattering","volume":"362","author":"Chai","year":"2022","journal-title":"J. Mol. Liq."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10355","DOI":"10.1021\/acssuschemeng.8b01687","article-title":"Design of Functional Therapeutic Deep Eutectic Solvents Based on Choline Chloride and Ascorbic Acid","volume":"6","author":"Silva","year":"2018","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106913","DOI":"10.1016\/j.catcom.2024.106913","article-title":"The choline chloride-based DES as a capable and new catalyst for the synthesis of benzopyranophenazinecarbonitriles","volume":"187","author":"Monem","year":"2024","journal-title":"Catal. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112268","DOI":"10.1016\/j.fct.2021.112268","article-title":"Tanacetum vulgare L. (Tansy) as an effective bioresource with promising pharmacological effects from natural arsenal","volume":"153","author":"Ak","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"120937","DOI":"10.1016\/j.molliq.2022.120937","article-title":"Characterization of eutectic mixtures of sugars and sugar-alcohols for cryopreservation","volume":"371","author":"Joules","year":"2023","journal-title":"J. Mol. Liq."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ibrahim, A., Tshibangu, M.M., Coquelet, C., and Espitalier, F. (2025). Ternary Choline Chloride-Based Deep Eutectic Solvents: A Review. ChemEngineering, 9.","DOI":"10.3390\/chemengineering9040084"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1023\/A:1018947113238","article-title":"Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: A mathematical model","volume":"10","author":"Oh","year":"1993","journal-title":"Pharm. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1023\/A:1016212804288","article-title":"A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability","volume":"12","author":"Amidon","year":"1995","journal-title":"Pharm. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8497","DOI":"10.1039\/D4GC00532E","article-title":"Deep eutectic solvents towards green polymeric materials","volume":"26","author":"Weerasinghe","year":"2024","journal-title":"Green Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"123605","DOI":"10.1016\/j.molliq.2023.123605","article-title":"Deep eutectic solvents: A long\u2013term approach to chemical synthesis and separation","volume":"393","author":"Verma","year":"2024","journal-title":"J. Mol. Liq."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1080\/10837450.2020.1735414","article-title":"Deep eutectic solvents for pharmaceutical formulation and drug delivery applications","volume":"25","author":"Emami","year":"2020","journal-title":"Pharm. Dev. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"123171","DOI":"10.1016\/j.molliq.2023.123171","article-title":"Exploring the potential of deep eutectic solvents in pharmaceuticals: Challenges and opportunities","volume":"390","author":"Shah","year":"2023","journal-title":"J. Mol. Liq."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Quodbach, J., Preis, E., Karkossa, F., Winck, J., Finke, J.H., and Steiner, D. (2025). Novel Strategies for the Formulation of Poorly Water-Soluble Drug Substances by Different Physical Modification Strategies with a Focus on Peroral Applications. Pharmaceuticals, 18.","DOI":"10.3390\/ph18081089"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100189","DOI":"10.1016\/j.sampre.2025.100189","article-title":"The complex world of eutectic solvents: Guidelines for a correct characterization and use in sample preparation","volume":"14","author":"Bosco","year":"2025","journal-title":"Adv. Sample Prep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s42004-024-01116-3","article-title":"Estimating the phase diagrams of deep eutectic solvents within an extensive chemical space","volume":"7","author":"Fajar","year":"2024","journal-title":"Commun. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1021\/acs.jchemed.0c00204","article-title":"Construction of a Room-Temperature Eutectic Binary Phase Diagram by Use of Differential Scanning Calorimetry","volume":"97","author":"Joos","year":"2020","journal-title":"J. Chem. Educ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15317","DOI":"10.1021\/acssuschemeng.0c05518","article-title":"Eutectic Mixtures Based on Polyalcohols as Sustainable Solvents: Screening and Characterization","volume":"8","author":"Silva","year":"2020","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18712","DOI":"10.1021\/acssuschemeng.0c08288","article-title":"Physicochemical Properties of Choline Chloride-Based Deep Eutectic Solvents with Polyols: An Experimental and Theoretical Investigation","volume":"8","author":"Biernacki","year":"2020","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Palmelund, H., Rantanen, J., and L\u00f6bmann, K. (2021). Deliquescence Behavior of Deep Eutectic Solvents. Appl. Sci., 11.","DOI":"10.3390\/app11041601"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"113347","DOI":"10.1016\/j.molliq.2020.113347","article-title":"The study of extent of interactions between components of natural deep eutectic solvents in the presence of water through isopiestic investigations","volume":"311","author":"Shekaari","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e202300669","DOI":"10.1002\/cssc.202300669","article-title":"Deep Eutectic Solvents: An Eco-friendly Design for Drug Engineering","volume":"16","author":"Oyoun","year":"2023","journal-title":"ChemSusChem"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1021\/mp049938f","article-title":"Physical Stability and Solubility Advantage from Amorphous Celecoxib:\u2009 The Role of Thermodynamic Quantities and Molecular Mobility","volume":"1","author":"Gupta","year":"2004","journal-title":"Mol. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.xphs.2016.05.001","article-title":"Interrelationships Between Structure and the Properties of Amorphous Solids of Pharmaceutical Interest","volume":"106","author":"Zografi","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6684","DOI":"10.1038\/s41467-023-42267-6","article-title":"Defying decomposition: The curious case of choline chloride","volume":"14","author":"Avila","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"123563","DOI":"10.1016\/j.molliq.2023.123563","article-title":"Structure and interactions in reline (1:2 Choline chloride\u2014Urea mixture) according to quantum chemical calculations and molecular dynamics simulation","volume":"393","author":"Krestyaninov","year":"2024","journal-title":"J. Mol. Liq."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"044308","DOI":"10.1063\/5.0052569","article-title":"A comprehensive computational and principal component analysis on various choline chloride-based deep eutectic solvents to reveal their structural and spectroscopic properties","volume":"155","author":"Rain","year":"2021","journal-title":"J. Chem. Phys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"138427","DOI":"10.1016\/j.cplett.2021.138427","article-title":"Theoretical investigation of supramolecular hydrogen-bonded choline chloride-based deep eutectic solvents using density functional theory","volume":"769","author":"Naseem","year":"2021","journal-title":"Chem. Phys. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.molliq.2018.10.150","article-title":"Deep eutectic solvents formed by quaternary ammonium salts and aprotic organic compound succinonitrile","volume":"274","author":"Yang","year":"2019","journal-title":"J. Mol. Liq."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"115381","DOI":"10.1016\/j.jpba.2023.115381","article-title":"Measurement of Moisture Content in Pharmaceutical Tablets by Handheld Near-Infrared Spectrometer: Adopting Quality by Design Approach to Analytical Method Lifecycle Management","volume":"229","author":"Patel","year":"2023","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.foodchem.2017.06.046","article-title":"Water activity in liquid food systems: A molecular scale interpretation","volume":"237","author":"Maneffa","year":"2017","journal-title":"Food Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"123728","DOI":"10.1016\/j.molliq.2023.123728","article-title":"Acidity and pH of DES-like mixtures and the possibilities of their determination","volume":"394","year":"2024","journal-title":"J. Mol. Liq."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"118031","DOI":"10.1016\/j.molliq.2021.118031","article-title":"Tuning refractive index of deep eutectic solvents","volume":"348","author":"Chen","year":"2022","journal-title":"J. Mol. Liq."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"115843","DOI":"10.1016\/j.molliq.2021.115843","article-title":"Refractive index prediction of deep eutectic solvents by molecular approaches","volume":"332","author":"Khajeh","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"25582","DOI":"10.1021\/acsomega.3c03502","article-title":"Refractive Index of 48 Neat Deep Eutectic Solvents and of Selected Mixtures: Effect of Temperature, Hydrogen-Bonding Donors, Hydrogen-Bonding Acceptors, Mole Ratio, and Water","volume":"8","author":"Luan","year":"2023","journal-title":"ACS Omega"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.molliq.2017.11.054","article-title":"The friction theory for modeling the viscosities of deep eutectic solvents using the CPA and PC-SAFT equations of state","volume":"249","author":"Haghbakhsh","year":"2018","journal-title":"J. Mol. Liq."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1002\/cphc.200400190","article-title":"Application of Hole Theory to the Viscosity of Ionic and Molecular Liquids","volume":"5","author":"Abbott","year":"2004","journal-title":"ChemPhysChem"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1021\/acs.jced.3c00706","article-title":"Choline Chloride- and Organic Acids-Based Deep Eutectic Solvents: Exploring Chemical and Thermophysical Properties","volume":"69","author":"Pinho","year":"2024","journal-title":"J. Chem. Eng. Data"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.molliq.2017.04.052","article-title":"Design, synthesis and properties of acidic deep eutectic solvents based on choline chloride","volume":"236","author":"Cui","year":"2017","journal-title":"J. Mol. Liq."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ijardar, S.P., Singh, V., and Gardas, R.L. (2022). Revisiting the Physicochemical Properties and Applications of Deep Eutectic Solvents. Molecules, 27.","DOI":"10.3390\/molecules27041368"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"113992","DOI":"10.1016\/j.molliq.2020.113992","article-title":"Sugar-based natural deep eutectic solvents as potential absorbents for NH3 capture at elevated temperatures and reduced pressures","volume":"317","author":"Li","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sarragu\u00e7a, M.C., Ribeiro, P.R.S., Nunes, C., and Seabra, C.L. (2022). Solids Turn into Liquids-Liquid Eutectic Systems of Pharmaceutics to Improve Drug Solubility. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030279"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.powtec.2014.05.044","article-title":"Experimental study of the viscosity of suspensions: Effect of solid fraction, particle size and suspending liquid","volume":"266","author":"Konijn","year":"2014","journal-title":"Powder Technol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Trombino, S., Siciliano, C., Procopio, D., Curcio, F., Lagan\u00e0, A.S., Di Gioia, M.L., and Cassano, R. (2022). Deep Eutectic Solvents for Improving the Solubilization and Delivery of Dapsone. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14020333"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Nica, M.-A., Anu\u021ba, V., Nicolae, C.A., Popa, L., Ghica, M.V., Coco\u0219, F.-I., and Dinu-P\u00eervu, C.-E. (2024). Exploring Deep Eutectic Solvents as Pharmaceutical Excipients: Enhancing the Solubility of Ibuprofen and Mefenamic Acid. Pharmaceuticals, 17.","DOI":"10.3390\/ph17101316"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8295","DOI":"10.1039\/D4SC02089H","article-title":"Semi-crystalline polymers with supramolecular synergistic interactions: From mechanical toughening to dynamic smart materials","volume":"15","author":"Shi","year":"2024","journal-title":"Chem. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6848","DOI":"10.1021\/acs.est.0c06803","article-title":"Effect of Water pH on the Uptake of Acidic (Ibuprofen) and Basic (Propranolol) Drugs in a Fish Gill Cell Culture Model","volume":"55","author":"Chang","year":"2021","journal-title":"Environ. Sci. Technol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"127544","DOI":"10.1016\/j.molliq.2025.127544","article-title":"Understanding the Solubility behaviour of Ibuprofen and Xylitol in Natural Deep Eutectic Systems through Hansen Solubility Parameters and Physicochemical Properties","volume":"428","author":"Fernandes","year":"2025","journal-title":"J. Mol. Liq."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101617","DOI":"10.1016\/j.imu.2025.101617","article-title":"Structural modification of Naproxen; physicochemical, spectral, medicinal, and pharmacological evaluation","volume":"53","author":"Farque","year":"2025","journal-title":"Inform. Med. Unlocked"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jpba.2005.11.029","article-title":"Simultaneous effect of cyclodextrin complexation, pH, and hydrophilic polymers on naproxen solubilization","volume":"42","author":"Cirri","year":"2006","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zhang, X.-R., Wu, B.-L., Han, J.-J., and Li, J.-Q. (2024). Simultaneous Improvement in Dissolution Behavior and Oral Bioavailability of Naproxen via Salt Formation. Crystals, 14.","DOI":"10.3390\/cryst14121104"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Thomas, S.D., Jha, N.K., Jha, S.K., Sadek, B., and Ojha, S. (2023). Pharmacological and Molecular Insight on the Cardioprotective Role of Apigenin. Nutrients, 15.","DOI":"10.3390\/nu15020385"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1021\/js960383s","article-title":"Evaluation of properties of apigenin and [G-3H] apigenin and analytic method development","volume":"86","author":"Li","year":"1997","journal-title":"J. Pharm. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"104327","DOI":"10.1016\/j.jddst.2023.104327","article-title":"Ibuprofen solubility and cytotoxic study of deep eutectic solvents formed by xylitol, choline chloride and water","volume":"82","author":"Lomba","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"113508","DOI":"10.1016\/j.fluid.2022.113508","article-title":"Experimental determination and correlation of naproxen solubility in biodegradable low-toxic betaine-based deep eutectic solvents and water mixtures at 293.15 K to 313.15 K","volume":"560","author":"Jafari","year":"2022","journal-title":"Fluid Phase Equilibria"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3110\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:28:10Z","timestamp":1774859290000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,29]]},"references-count":67,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27073110"],"URL":"https:\/\/doi.org\/10.3390\/ijms27073110","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,29]]}}}