{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T21:11:56Z","timestamp":1787865116452,"version":"build-2784847793"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The aim of this study is to investigate the solubility of methyldopa in supercritical carbon dioxide. Solubility was examined at temperatures of 338, 328, 318, and 308\u00a0K, in both the presence and absence of a co-solvent. Specifically, ethanol was evaluated as a co-solvent. Semi-empirical and empirical approaches, as well as the Peng-Robinson equation, were applied to analyze the experimental data. The mole fraction (solubility) of methyldopa was found to range from 0.078\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup> (0.21\u00a0g\/l) to 1.082\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup> (3.38\u00a0g\/l) in the binary system and from 0.405\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup> (1.38\u00a0g\/l) to 3.143\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup> (11.33\u00a0g\/l) as well as from 1.225\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup> (4.60\u00a0g\/l) to 8.979\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup> (34.94\u00a0g\/l) at 1 and 3\u00a0mol % respectively. The findings indicated that incorporating a co-solvent, particularly ethanol, resulted in a substantial enhancement in solubility. The maximum enhancement was recorded in the methyldopa-ethanol-CO<jats:sub>2<\/jats:sub> system at 12\u00a0MPa and 338\u00a0K, where the solubility was found to be 15.70 times higher than in pure supercritical carbon dioxide. The models employed for data evaluation exhibited robust correlations with the experimental outcomes. Among these models, the Soltani-Mazloumi model exhibited the strongest correlation with the experimental solubility data.<\/jats:p>","DOI":"10.1038\/s41598-025-15596-3","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T22:38:26Z","timestamp":1755038306000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enhancing methyldopa solubility via green supercritical fluid techniques using ethanol co-solvent"],"prefix":"10.1038","volume":"15","author":[{"given":"Hadil Faris","family":"Alotaibi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suleiman Ibrahim","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asokan","family":"Vasudevan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suranjana V.","family":"Mayani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhas","family":"Ballal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munthar Kadhim","family":"Abosaoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhayveer","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhashree","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atreyi","family":"Pramanik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"15596_CR1","doi-asserted-by":"publisher","first-page":"110196","DOI":"10.1016\/j.biopha.2020.110196","volume":"127","author":"M Wici\u0144ski","year":"2020","unstructured":"Wici\u0144ski, M., Malinowski, B., Puk, O., Socha, M. & S\u0142upski, M. Methyldopa as an inductor of postpartum depression and maternal blues: A review. Biomed. Pharmacother. 127, 110196. https:\/\/doi.org\/10.1016\/j.biopha.2020.110196 (2020).","journal-title":"Biomed. Pharmacother."},{"key":"15596_CR2","doi-asserted-by":"publisher","first-page":"221","DOI":"10.2165\/00003088-198207030-00003","volume":"7","author":"E Myhre","year":"1982","unstructured":"Myhre, E., Rugstad, H. E. & Hansen, T. Clinical pharmacokinetics of Methyldopa. Clin. Pharmacokinet. 7, 221\u2013233. https:\/\/doi.org\/10.2165\/00003088-198207030-00003 (1982).","journal-title":"Clin. Pharmacokinet."},{"key":"15596_CR3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ajps.2014.08.005","volume":"10","author":"VB Junyaprasert","year":"2015","unstructured":"Junyaprasert, V. B. & Morakul, B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J. Pharm. Sci. 10, 13\u201323. https:\/\/doi.org\/10.1016\/j.ajps.2014.08.005 (2015).","journal-title":"Asian J. Pharm. Sci."},{"key":"15596_CR4","first-page":"304","volume":"9","author":"P Khadka","year":"2014","unstructured":"Khadka, P. et al. Pharmaceutical particle technologies: an approach to improve drug solubility, dissolution and bioavailability. Asian J. Pharm. Sci. 9, 304\u2013316 (2014).","journal-title":"Asian J. Pharm. Sci."},{"key":"15596_CR5","doi-asserted-by":"publisher","first-page":"28","DOI":"10.4172\/jbb.1000027","volume":"2","author":"YS Krishnaiah","year":"2010","unstructured":"Krishnaiah, Y. S. Pharmaceutical technologies for enhancing oral bioavailability of poorly soluble drugs. J. Bioequiv Availab. 2, 28\u201336 (2010).","journal-title":"J. Bioequiv Availab."},{"key":"15596_CR6","doi-asserted-by":"crossref","unstructured":"Esfandiari, N. & Sajadian, S. A. CO2 utilization as gas antisolvent for the pharmaceutical micro and nanoparticle production: A review. Arabian J. Chemistry, 104164 (2022).","DOI":"10.1016\/j.arabjc.2022.104164"},{"key":"15596_CR7","doi-asserted-by":"crossref","unstructured":"Kankala, R. K., Xu, P. Y., Chen, B. Q., Wang, S. B. & Chen, A. Z. Supercritical fluid (SCF)-assisted fabrication of carrier-free drugs: an eco-friendly welcome to active pharmaceutical ingredients (APIs). Advanced Drug Delivery Reviews, 113846 (2021).","DOI":"10.1016\/j.addr.2021.113846"},{"key":"15596_CR8","doi-asserted-by":"crossref","unstructured":"Padrela, L. et al. Supercritical carbon dioxide-based technologies for the production of drug nanoparticles\/nanocrystals\u2013A comprehensive review. Advanced Drug Delivery Reviews (2018).","DOI":"10.1016\/j.addr.2018.07.010"},{"key":"15596_CR9","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.energy.2014.07.044","volume":"77","author":"\u017d Knez","year":"2014","unstructured":"Knez, \u017d. et al. Industrial applications of supercritical fluids: A review. Energy 77, 235\u2013243 (2014).","journal-title":"Energy"},{"key":"15596_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.supflu.2018.11.007","author":"G Sodeifian","year":"2018","unstructured":"Sodeifian, G., Sajadian, S. A., Ardestani, N. S. & Razmimanesh, F. Production of Loratadine drug nanoparticles using ultrasonic-assisted rapid expansion of supercritical solution into aqueous solution (US-RESSAS). J. Supercrit. Fluids. https:\/\/doi.org\/10.1016\/j.supflu.2018.11.007 (2018).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR11","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.supflu.2015.05.013","volume":"107","author":"A Fattahi","year":"2016","unstructured":"Fattahi, A. et al. Preparation and characterization of Simvastatin nanoparticles using rapid expansion of supercritical solution (RESS) with trifluoromethane. J. Supercrit. Fluids. 107, 469\u2013478 (2016).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.supflu.2016.06.001","volume":"116","author":"M T\u00fcrk","year":"2016","unstructured":"T\u00fcrk, M. & Bolten, D. Polymorphic properties of micronized mefenamic acid, nabumetone, Paracetamol and tolbutamide produced by rapid expansion of supercritical solutions (RESS). J. Supercrit. Fluids. 116, 239\u2013250 (2016).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR13","doi-asserted-by":"publisher","first-page":"117899","DOI":"10.1016\/j.molliq.2021.117899","volume":"346","author":"G Sodeifian","year":"2022","unstructured":"Sodeifian, G., Alwi, R. S., Razmimanesh, F. & Abadian, M. Solubility of dasatinib monohydrate (anticancer drug) in supercritical CO2: experimental and thermodynamic modeling. J. Mol. Liq. 346, 117899 (2022).","journal-title":"J. Mol. Liq."},{"key":"15596_CR14","doi-asserted-by":"publisher","first-page":"114539","DOI":"10.1016\/j.molliq.2020.114539","volume":"322","author":"M Pishnamazi","year":"2021","unstructured":"Pishnamazi, M. et al. Chloroquine (antimalaria medication with anti SARS-CoV activity) solubility in supercritical carbon dioxide. J. Mol. Liq. 322, 114539 (2021).","journal-title":"J. Mol. Liq."},{"key":"15596_CR15","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.jiec.2018.01.017","volume":"62","author":"N Wichianphong","year":"2018","unstructured":"Wichianphong, N. & Charoenchaitrakool, M. Statistical optimization for production of mefenamic acid\u2013nicotinamide cocrystals using gas anti-solvent (GAS) process. J. Ind. Eng. Chem. 62, 375\u2013382 (2018).","journal-title":"J. Ind. Eng. Chem."},{"key":"15596_CR16","doi-asserted-by":"publisher","first-page":"106165","DOI":"10.1016\/j.supflu.2023.106165","volume":"206","author":"F Arabgol","year":"2024","unstructured":"Arabgol, F., Amani, M., Ardestani, N. S. & Sajadian, S. A. Experimental and thermodynamic investigation of Gemifloxacin solubility in supercritical CO2 for the production of nanoparticles. J. Supercrit. Fluids. 206, 106165 (2024).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR17","doi-asserted-by":"crossref","unstructured":"Ansari, E., Honarvar, B., Sajadian, S. A., Aboosadi, Z. A. & Azizi, M. Solubility of Aripiprazole in supercritical carbon dioxide: Experimental and modeling evaluations. (2023).","DOI":"10.21203\/rs.3.rs-2823895\/v1"},{"key":"15596_CR18","doi-asserted-by":"publisher","first-page":"113880","DOI":"10.1016\/j.fluid.2023.113880","volume":"574","author":"RS Alwi","year":"2023","unstructured":"Alwi, R. S. et al. Experimental study and thermodynamic modeling of clonazepam solubility in supercritical carbon dioxide. Fluid. Phase. Equilibria. 574, 113880. https:\/\/doi.org\/10.1016\/j.fluid.2023.113880 (2023).","journal-title":"Fluid. Phase. Equilibria"},{"key":"15596_CR19","doi-asserted-by":"publisher","first-page":"113677","DOI":"10.1016\/j.fluid.2022.113677","volume":"566","author":"B Honarvar","year":"2023","unstructured":"Honarvar, B., Sajadian, S. A., Rojas, A., Galotto, M. J. & Jouyban, A. Solubility and thermodynamic modeling of sildenafil citrate in supercritical carbon dioxide. Fluid. Phase. Equilibria. 566, 113677. https:\/\/doi.org\/10.1016\/j.fluid.2022.113677 (2023).","journal-title":"Fluid. Phase. Equilibria"},{"key":"15596_CR20","doi-asserted-by":"publisher","first-page":"119467","DOI":"10.1016\/j.molliq.2022.119467","volume":"360","author":"N Esfandiari","year":"2022","unstructured":"Esfandiari, N. & Sajadian, S. A. Solubility of lacosamide in supercritical carbon dioxide: an experimental analysis and thermodynamic modeling. J. Mol. Liq. 360, 119467 (2022).","journal-title":"J. Mol. Liq."},{"key":"15596_CR21","doi-asserted-by":"publisher","first-page":"112422","DOI":"10.1016\/j.fluid.2019.112422","volume":"507","author":"G Sodeifian","year":"2020","unstructured":"Sodeifian, G., Sajadian, S. A. & Derakhsheshpour, R. Experimental measurement and thermodynamic modeling of Lansoprazole solubility in supercritical carbon dioxide: application of SAFT-VR EoS. Fluid. Phase. Equilibria. 507, 112422 (2020).","journal-title":"Fluid. Phase. Equilibria"},{"key":"15596_CR22","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1021\/acs.jced.9b01069","volume":"65","author":"G Sodeifian","year":"2020","unstructured":"Sodeifian, G., Saadati Ardestani, N., Sajadian, S. A., Golmohammadi, M. R. & Fazlali, A. Prediction of solubility of sodium valproate in supercritical carbon dioxide: experimental study and thermodynamic modeling. J. Chem. Eng. Data. 65, 1747\u20131760 (2020).","journal-title":"J. Chem. Eng. Data"},{"key":"15596_CR23","doi-asserted-by":"crossref","unstructured":"Sodeifian, G., Razmimanesh, F. & Sajadian, S. A. Solubility measurement of a chemotherapeutic agent (Imatinib mesylate) in supercritical carbon dioxide: assessment of new empirical model. The J. Supercritical Fluids (2019).","DOI":"10.1016\/j.supflu.2019.01.006"},{"key":"15596_CR24","doi-asserted-by":"publisher","first-page":"107050","DOI":"10.1016\/j.jct.2023.107050","volume":"182","author":"G Sodeifian","year":"2023","unstructured":"Sodeifian, G., Nasri, L., Razmimanesh, F. & Nooshabadi, M. A. Solubility of ibrutinib in supercritical carbon dioxide (Sc-CO2): data correlation and thermodynamic analysis. J. Chem. Thermodyn. 182, 107050 (2023).","journal-title":"J. Chem. Thermodyn."},{"key":"15596_CR25","doi-asserted-by":"publisher","first-page":"7758","DOI":"10.1038\/s41598-022-11887-1","volume":"12","author":"G Sodeifian","year":"2022","unstructured":"Sodeifian, G., Garlapati, C., Razmimanesh, F. & Nateghi, H. Solubility measurement and thermodynamic modeling of Pantoprazole sodium sesquihydrate in supercritical carbon dioxide. Sci. Rep. 12, 7758 (2022).","journal-title":"Sci. Rep."},{"key":"15596_CR26","doi-asserted-by":"publisher","first-page":"113954","DOI":"10.1016\/j.molliq.2020.113954","volume":"317","author":"M Pishnamazi","year":"2020","unstructured":"Pishnamazi, M. et al. Measuring solubility of a chemotherapy-anti cancer drug (busulfan) in supercritical carbon dioxide. J. Mol. Liq. 317, 113954 (2020).","journal-title":"J. Mol. Liq."},{"key":"15596_CR27","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.fluid.2015.12.017","volume":"411","author":"XQ Bian","year":"2016","unstructured":"Bian, X. Q., Zhang, Q., Du, Z. M., Chen, J. & Jaubert, J. N. A five-parameter empirical model for correlating the solubility of solid compounds in supercritical carbon dioxide. Fluid. Phase. Equilibria. 411, 74\u201380 (2016).","journal-title":"Fluid. Phase. Equilibria"},{"key":"15596_CR28","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1063\/1.555893","volume":"20","author":"KD Bartle","year":"1991","unstructured":"Bartle, K. D., Clifford, A., Jafar, S. & Shilstone, G. Solubilities of solids and liquids of low volatility in supercritical carbon dioxide. J. Phys. Chem. Ref. Data. 20, 713\u2013756 (1991).","journal-title":"J. Phys. Chem. Ref. Data"},{"key":"15596_CR29","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/S0378-3812(99)00154-5","volume":"158","author":"J M\u00e9ndez-Santiago","year":"1999","unstructured":"M\u00e9ndez-Santiago, J. & Teja, A. S. The solubility of solids in supercritical fluids. Fluid. Phase. Equilibria. 158, 501\u2013510 (1999).","journal-title":"Fluid. Phase. Equilibria"},{"key":"15596_CR30","doi-asserted-by":"publisher","first-page":"4767","DOI":"10.1021\/ie000339u","volume":"39","author":"J Mendez-Santiago","year":"2000","unstructured":"Mendez-Santiago, J. & Teja, A. S. Solubility of solids in supercritical fluids: consistency of data and a new model for cosolvent systems. Ind. Eng. Chem. Res. 39, 4767\u20134771 (2000).","journal-title":"Ind. Eng. Chem. Res."},{"key":"15596_CR31","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1021\/ie00080a036","volume":"27","author":"JM Del Valle","year":"1988","unstructured":"Del Valle, J. M. & Aguilera, J. M. An improved equation for predicting the solubility of vegetable oils in supercritical carbon dioxide. Ind. Eng. Chem. Res. 27, 1551\u20131553 (1988).","journal-title":"Ind. Eng. Chem. Res."},{"key":"15596_CR32","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.tca.2009.12.004","volume":"500","author":"C Garlapati","year":"2010","unstructured":"Garlapati, C. & Madras, G. New empirical expressions to correlate solubilities of solids in supercritical carbon dioxide. Thermochim Acta. 500, 123\u2013127 (2010).","journal-title":"Thermochim Acta"},{"key":"15596_CR33","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/0896-8446(88)90005-8","volume":"1","author":"SK Kumar","year":"1988","unstructured":"Kumar, S. K. & Johnston, K. P. Modelling the solubility of solids in supercritical fluids with density as the independent variable. J. Supercrit. Fluids. 1, 15\u201322 (1988).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR34","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/S0021-9673(00)01120-1","volume":"910","author":"JC Gonz\u00e1lez","year":"2001","unstructured":"Gonz\u00e1lez, J. C., Vieytes, M. R., Botana, A. M., Vieites, J. M. & Botana, L. M. Modified mass action law-based model to correlate the solubility of solids and liquids in entrained supercritical carbon dioxide. J. Chromatogr. A. 910, 119\u2013125 (2001).","journal-title":"J. Chromatogr. A"},{"key":"15596_CR35","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.supflu.2016.05.015","volume":"116","author":"G Sodeifian","year":"2016","unstructured":"Sodeifian, G., Sajadian, S. A. & Ardestani, N. S. Optimization of essential oil extraction from launaea acanthodes boiss: utilization of supercritical carbon dioxide and cosolvent. J. Supercrit. Fluids. 116, 46\u201356 (2016).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR36","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.supflu.2013.11.017","volume":"93","author":"A Tabernero","year":"2014","unstructured":"Tabernero, A., de Melo, S. V., Mammucari, R., del Valle, E. M. & Foster, N. Modelling solubility of solid active principle ingredients in sc-CO 2 with and without cosolvents: A comparative assessment of semiempirical models based on chrastil\u2019s equation and its modifications. J. Supercrit. Fluids. 93, 91\u2013102 (2014).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR37","doi-asserted-by":"publisher","first-page":"3359","DOI":"10.1021\/je500345n","volume":"59","author":"C Tang","year":"2014","unstructured":"Tang, C., Guan, Y. X., Yao, S. J. & Zhu, Z. Q. Solubility of dexamethasone in supercritical carbon dioxide with and without a cosolvent. J. Chem. Eng. Data. 59, 3359\u20133364 (2014).","journal-title":"J. Chem. Eng. Data"},{"key":"15596_CR38","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.supflu.2010.09.002","volume":"55","author":"MH Hosseini","year":"2010","unstructured":"Hosseini, M. H., Alizadeh, N. & Khanchi, A. R. Effect of menthol as solid cosolvent on the solubility enhancement of clozapine and lamorigine in supercritical CO2. J. Supercrit. Fluids. 55, 14\u201322 (2010).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR39","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1021\/je8003673","volume":"53","author":"CC Tsai","year":"2008","unstructured":"Tsai, C. C., Lin, H. & Lee, M. J. Solubility of CI disperse Violet 1 in supercritical carbon dioxide with or without cosolvent. J. Chem. Eng. Data. 53, 2163\u20132169 (2008).","journal-title":"J. Chem. Eng. Data"},{"key":"15596_CR40","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0896-8446(03)00116-5","volume":"30","author":"Z Huang","year":"2004","unstructured":"Huang, Z., Kawi, S. & Chiew, Y. Solubility of cholesterol and its esters in supercritical carbon dioxide with and without cosolvents. J. Supercrit. Fluids. 30, 25\u201339 (2004).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR41","doi-asserted-by":"publisher","first-page":"114165","DOI":"10.1016\/j.fluid.2024.114165","volume":"585","author":"A Rojas","year":"2024","unstructured":"Rojas, A. et al. Solubility of Oxazepam in supercritical carbon dioxide: experimental and modeling. Fluid. Phase. Equilibria. 585, 114165. https:\/\/doi.org\/10.1016\/j.fluid.2024.114165 (2024).","journal-title":"Fluid. Phase. Equilibria"},{"key":"15596_CR42","doi-asserted-by":"publisher","first-page":"114284","DOI":"10.1016\/j.fluid.2024.114284","volume":"590","author":"M Askarizadeh","year":"2025","unstructured":"Askarizadeh, M., Esfandiari, N., Honarvar, B., Sajadian, S. A. & Azdarpour, A. Solubility of Teriflunomide in supercritical carbon dioxide and co-solvent investigation. Fluid. Phase. Equilibria. 590, 114284. https:\/\/doi.org\/10.1016\/j.fluid.2024.114284 (2025).","journal-title":"Fluid. Phase. Equilibria"},{"key":"15596_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-021-87243-6","volume":"11","author":"G Sodeifian","year":"2021","unstructured":"Sodeifian, G., Sajadian, S. A., Razmimanesh, F. & Hazaveie, S. M. Solubility of ketoconazole (antifungal drug) in SC-CO2 for binary and ternary systems: measurements and empirical correlations. Sci. Rep. 11, 1\u201313 (2021).","journal-title":"Sci. Rep."},{"key":"15596_CR44","doi-asserted-by":"publisher","unstructured":"Soltani, S. & Mazloumi, S. H. A new empirical model to correlate solute solubility in supercritical carbon dioxide in presence of co-solvent. Chem. Eng. Res. Des. 125 https:\/\/doi.org\/10.1016\/j.cherd.2017.07.006 (2017).","DOI":"10.1016\/j.cherd.2017.07.006"},{"key":"15596_CR45","doi-asserted-by":"publisher","unstructured":"Garlapati, C. & Madras, G. Solubilities of solids in supercritical fluids using dimensionally consistent modified solvate complex models. Fluid Phase Equilib. 283 https:\/\/doi.org\/10.1016\/j.fluid.2009.05.013 (2009).","DOI":"10.1016\/j.fluid.2009.05.013"},{"key":"15596_CR46","doi-asserted-by":"publisher","unstructured":"Jouyban, A., Khoubnasabjafari, M. & Chan, H. K. Modeling the entrainer effects on solubility of solutes in supercritical carbon dioxide. Chem. Pharm. Bull. 53 https:\/\/doi.org\/10.1248\/cpb.53.290 (2005).","DOI":"10.1248\/cpb.53.290"},{"key":"15596_CR47","doi-asserted-by":"publisher","first-page":"3016","DOI":"10.1021\/j100212a041","volume":"86","author":"J Chrastil","year":"1982","unstructured":"Chrastil, J. Solubility of solids and liquids in supercritical gases. J. Phys. Chem. 86, 3016\u20133021 (1982).","journal-title":"J. Phys. Chem."},{"key":"15596_CR48","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.cherd.2017.07.006","volume":"125","author":"S Soltani","year":"2017","unstructured":"Soltani, S. & Mazloumi, S. H. A new empirical model to correlate solute solubility in supercritical carbon dioxide in presence of co-solvent. Chem. Eng. Res. Des. 125, 79\u201387 (2017).","journal-title":"Chem. Eng. Res. Des."},{"key":"15596_CR49","doi-asserted-by":"publisher","first-page":"2734","DOI":"10.1016\/j.cherd.2014.01.026","volume":"92","author":"SB Hozhabr","year":"2014","unstructured":"Hozhabr, S. B., Mazloumi, S. H. & Sargolzaei, J. Correlation of solute solubility in supercritical carbon dioxide using a new empirical equation. Chem. Eng. Res. Des. 92, 2734\u20132739 (2014).","journal-title":"Chem. Eng. Res. Des."},{"key":"15596_CR50","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1248\/cpb.53.290","volume":"53","author":"A Jouyban","year":"2005","unstructured":"Jouyban, A., Khoubnasabjafari, M. & Chan, H. K. Modeling the entrainer effects on solubility of solutes in supercritical carbon dioxide. Chem. Pharm. Bull. 53, 290\u2013295 (2005).","journal-title":"Chem. Pharm. Bull."},{"key":"15596_CR51","doi-asserted-by":"publisher","unstructured":"Immirzi, A. & Perini, B. Prediction of density in organic crystals. Acta Crystallogr. Sect. A. 33 https:\/\/doi.org\/10.1107\/S0567739477000448 (1977).","DOI":"10.1107\/S0567739477000448"},{"key":"15596_CR52","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/s41598-024-84263-w","volume":"15","author":"AF Wali","year":"2025","unstructured":"Wali, A. F. et al. Determination of the solubility of Methyldopa in supercritical carbon dioxide for drug delivery applications: thermal analysis. Sci. Rep. 15, 923 (2025).","journal-title":"Sci. Rep."},{"key":"15596_CR53","doi-asserted-by":"publisher","first-page":"3870","DOI":"10.1038\/s41598-025-86004-z","volume":"15","author":"SA Sajadian","year":"2025","unstructured":"Sajadian, S. A. et al. Mesalazine solubility in supercritical carbon dioxide with and without cosolvent and modeling. Sci. Rep. 15, 3870. https:\/\/doi.org\/10.1038\/s41598-025-86004-z (2025).","journal-title":"Sci. Rep."},{"key":"15596_CR54","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1002\/ceat.202300449","volume":"47","author":"SA Sajadian","year":"2024","unstructured":"Sajadian, S. A., Esfandiari, N., Ardestani, S., Amani, N., Est\u00e9vez, L. A. & M. & Measurement and modeling of the solubility of Mebeverine hydrochloride in supercritical carbon dioxide. Chem. Eng. Technol. 47, 811\u2013821 (2024).","journal-title":"Chem. Eng. Technol."},{"key":"15596_CR55","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1021\/acs.jced.3c00587","volume":"69","author":"SA Sajadian","year":"2024","unstructured":"Sajadian, S. A. et al. Solubility Measurement and Correlation of Alprazolam in Carbon Dioxide with\/without Ethanol at Temperatures from 308 to 338 K and Pressures from 120 to 300 bar. J. Chem. Eng. Data. 69, 1718\u20131730. https:\/\/doi.org\/10.1021\/acs.jced.3c00587 (2024).","journal-title":"J. Chem. Eng. Data"},{"key":"15596_CR56","doi-asserted-by":"publisher","unstructured":"Bazaei, M., Honarvar, B., Esfandiari, N., Sajadian, S. A. & Arab Aboosadi, Z. Preparation of erlotinib hydrochloride nanoparticles (anti-cancer drug) by RESS-C method and investigating the effective parameters. Sci. Rep. 14 https:\/\/doi.org\/10.1038\/s41598-024-64477-8 (2024).","DOI":"10.1038\/s41598-024-64477-8"},{"key":"15596_CR57","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1021\/acs.jced.4c00407","volume":"70","author":"MA Khan","year":"2025","unstructured":"Khan, M. A. et al. Study of Baclofen solubility in supercritical CO2 with and without cosolvents: experimental analysis, thermodynamic evaluation, and machine learning methods. J. Chem. Eng. Data. 70, 953\u2013971. https:\/\/doi.org\/10.1021\/acs.jced.4c00407 (2025).","journal-title":"J. Chem. Eng. Data"},{"key":"15596_CR58","doi-asserted-by":"publisher","first-page":"105990","DOI":"10.1016\/j.supflu.2023.105990","volume":"200","author":"AP Kloc","year":"2023","unstructured":"Kloc, A. P., Danzer, A. & Sadowski, G. Solubility of Naproxen and indomethacin in supercritical carbon dioxide\/ethyl acetate mixtures. J. Supercrit. Fluids. 200, 105990. https:\/\/doi.org\/10.1016\/j.supflu.2023.105990 (2023).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR59","doi-asserted-by":"publisher","first-page":"103212","DOI":"10.1016\/j.csite.2023.103212","volume":"49","author":"AJ Obaidullah","year":"2023","unstructured":"Obaidullah, A. J. Thermodynamic and experimental analysis of drug nanoparticles Preparation using supercritical thermal processing: solubility of Chlorothiazide in different Co-solvents. Case Stud. Therm. Eng. 49, 103212. https:\/\/doi.org\/10.1016\/j.csite.2023.103212 (2023).","journal-title":"Case Stud. Therm. Eng."},{"key":"15596_CR60","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1021\/acs.jced.4c00208","volume":"69","author":"OS Alsawad","year":"2024","unstructured":"Alsawad, O. S. et al. Investigating the influence of cosolvents on the solubility of febuxostat in supercritical CO2: experimental analysis and artificial intelligence study. J. Chem. Eng. Data. 69, 2569\u20132584. https:\/\/doi.org\/10.1021\/acs.jced.4c00208 (2024).","journal-title":"J. Chem. Eng. Data"},{"key":"15596_CR61","doi-asserted-by":"crossref","unstructured":"Abadian, M., Sodeifian, G., Razmimanesh, F. & Zarei Mahmoudabadi, S. Experimental measurement and thermodynamic modeling of solubility of riluzole drug (neuroprotective agent) in supercritical carbon dioxide. Fluid Phase Equilib 567 (2023).","DOI":"10.1016\/j.fluid.2022.113711"},{"key":"15596_CR62","doi-asserted-by":"crossref","unstructured":"Sodeifian, G., Bagheri, H., Arbab Nooshabadi, M., Razmimanesh, F. & Roshanghias, A. Experimental solubility of Fexofenadine hydrochloride (antihistamine) drug in SC-CO2: evaluation of cubic equations of state. J Supercrit Fluids 200 (2023).","DOI":"10.1016\/j.supflu.2023.106000"},{"key":"15596_CR63","doi-asserted-by":"publisher","unstructured":"Askarizadeh, M., Esfandiari, N., Honarvar, B., Ali Sajadian, S. & Azdarpour, A. Binary and ternary approach of solubility of Rivaroxaban for Preparation of developed nano drug using supercritical fluid. Arab. J. Chem. 17 https:\/\/doi.org\/10.1016\/j.arabjc.2024.105707 (2024).","DOI":"10.1016\/j.arabjc.2024.105707"},{"key":"15596_CR64","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1021\/acs.jced.1c00829","volume":"67","author":"B Li","year":"2022","unstructured":"Li, B. et al. Cosolvent effect on the solubility of ammonium benzoate in supercritical carbon dioxide. J. Chem. Eng. Data. 67, 689\u2013694. https:\/\/doi.org\/10.1021\/acs.jced.1c00829 (2022).","journal-title":"J. Chem. Eng. Data"},{"key":"15596_CR65","doi-asserted-by":"crossref","unstructured":"Connelly, J. ICH Q3C impurities: guideline for residual solvents. ICH Qual. Guidelines: Implement. Guide, 199\u2013232 (2017).","DOI":"10.1002\/9781118971147.ch7"},{"key":"15596_CR66","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.supflu.2014.06.022","volume":"94","author":"LM Valenzuela","year":"2014","unstructured":"Valenzuela, L. M., Reveco-Chilla, A. G. & del Valle, J. M. Modeling solubility in supercritical carbon dioxide using quantitative structure\u2013property relationships. J. Supercrit. Fluids. 94, 113\u2013122 (2014).","journal-title":"J. Supercrit. Fluids"},{"key":"15596_CR67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.fluid.2018.10.020","volume":"482","author":"RG Bitencourt","year":"2019","unstructured":"Bitencourt, R. G., Palma, A. M., Coutinho, J. A., Cabral, F. A. & Meirelles, A. J. Prediction of solid solute solubility in supercritical CO2 with cosolvents using the CPA EoS. Fluid. Phase. Equilibria. 482, 1\u201310 (2019).","journal-title":"Fluid. Phase. Equilibria"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-15596-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-15596-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-15596-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T21:24:46Z","timestamp":1757453086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-15596-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,13]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["15596"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-15596-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,13]]},"assertion":[{"value":"16 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29615"}}