{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:20:32Z","timestamp":1790418032835,"version":"4.1.0"},"reference-count":107,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Cyclodextrins (CDs) are cyclic oligosaccharides that emerged as industrial excipients in the early 1970s and are currently found in at least 130 marketed pharmaceutical products, in addition to numerous other consumer products. Although CDs have been the subject of close to 100,000 publications since their discovery, and although their structure and properties appear to be trivial, CDs are constantly surprising investigators by their unique physicochemical properties. In aqueous solutions, CDs are solubilizing complexing agents of poorly soluble drugs while they can also act as organic cosolvents like ethanol. CDs and their complexes self-assemble in aqueous solutions to form both nano- and microparticles. The nanoparticles have diameters that are well below the wavelength of visible light; thus, the solutions appear to be clear. However, the nanoparticles can result in erroneous conclusions and misinterpretations of experimental results. CDs can act as penetration enhancers, increasing drug permeation through lipophilic membranes, but they do so without affecting the membrane barrier. This review is an account of some of the unexpected results the authors have encountered during their studies of CDs as pharmaceutical excipients.<\/jats:p>","DOI":"10.3390\/ma16062223","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T01:31:41Z","timestamp":1678411901000},"page":"2223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Anomalous Properties of Cyclodextrins and Their Complexes in Aqueous Solutions"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9439-1553","authenticated-orcid":false,"given":"Thorsteinn","family":"Loftsson","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4074-9182","authenticated-orcid":false,"given":"H\u00e1kon Hrafn","family":"Sigurdsson","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7114-8991","authenticated-orcid":false,"given":"Phatsawee","family":"Jansook","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phyathai Road, Pathumwan, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2006.10.044","article-title":"Cyclodextrins and their pharmaceutical applications","volume":"329","author":"Loftsson","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1248\/cpb.52.900","article-title":"Design and evaluation of cyclodextrin-based drug formulation","volume":"52","author":"Uekama","year":"2004","journal-title":"Chem. Pharm. Bull."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1556\/066.2021.00051","article-title":"Cyclodextrin in starchy foods","volume":"50","author":"Fenyvesi","year":"2021","journal-title":"Acta Aliment."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3311\/PPch.21222","article-title":"Recent list of cyclodextrin-containing drug products","volume":"67","author":"Szent","year":"2023","journal-title":"Period. Polytech. Chem. Eng."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/polysaccharides3010001","article-title":"Cyclodextrins: Structural, Chemical, and Physical Properties, and Applications","volume":"3","author":"Poulson","year":"2022","journal-title":"Polysaccharides"},{"key":"ref_6","first-page":"536","article-title":"Sur la fermentation de la f\u00e9cule par l\u2019action du ferment butyrique","volume":"112","author":"Villiers","year":"1891","journal-title":"Compt. Rend. Acad. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cramer, F. (1954). Einschlussverbindungen, Springer.","DOI":"10.1007\/978-3-642-49192-4"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1007\/s10311-020-01170-y","article-title":"Outstanding contribution of Professor Jozsef Szejtli to cyclodextrin applications in foods, cosmetics, drugs, chromatography and biotechnology: A review","volume":"19","author":"Crini","year":"2021","journal-title":"Environ. Chem. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"117620","DOI":"10.1016\/j.carbpol.2021.117620","article-title":"Contributions of Dexter French (1918\u20131981) to cycloamylose\/cyclodextrin and starch science","volume":"257","author":"Crini","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10940","DOI":"10.1021\/cr500081p","article-title":"Review: A History of Cyclodextrins","volume":"114","author":"Crini","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Krabicova, I., Appleton, S.L., Tannous, M., Hoti, G., Caldera, F., Pedrazzo, A.R., Cecone, C., Cavalli, R., and Trotta, F. (2020). History of cyclodextrin nanosponges. Polymers, 12.","DOI":"10.3390\/polym12051122"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1007\/s10311-020-01156-w","article-title":"130 years of cyclodextrin discovery for health, food, agriculture, and the industry: A review","volume":"19","author":"Fourmentin","year":"2021","journal-title":"Environ. Chem. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119396","DOI":"10.1016\/j.ijpharm.2020.119396","article-title":"Sulfobutylether-\u03b2-cyclodextrin","volume":"583","author":"Stella","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Saokham, P., Muankaew, C., Jansook, P., and Loftsson, T. (2018). Solubility of Cyclodextrins and Drug\/Cyclodextrin Complexes. Molecules, 23.","DOI":"10.3390\/molecules23051161"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s10847-020-01029-3","article-title":"Pharmaceutical applications of cyclodextrins and their derivatives","volume":"98","author":"Dhiman","year":"2020","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ejpb.2022.07.007","article-title":"Cyclodextrin-based delivery systems in parenteral formulations: A critical update review","volume":"178","author":"Ferreira","year":"2022","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.drudis.2015.11.016","article-title":"Cyclodextrins in pharmaceutical formulations II: Solubilization, binding constant, and complexation efficiency","volume":"21","author":"Jambhekar","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_18","first-page":"3788","article-title":"Pharmaceutical applications of cyclodextrins","volume":"16","author":"Zhao","year":"2016","journal-title":"Xiandai Shengwuyixue Jinzhan"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.drudis.2015.11.017","article-title":"Cyclodextrins in pharmaceutical formulations I: Structure and physicochemical properties, formation of complexes, and types of complex","volume":"21","author":"Jambhekar","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(98)00052-0","article-title":"Mechanisms of drug release from cyclodextrin complexes","volume":"36","author":"Stella","year":"1999","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_21","first-page":"117","article-title":"Phase Solubility Techniques","volume":"4","author":"Higuchi","year":"1965","journal-title":"Adv. Anal. Chem. Instrum."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.carres.2005.11.004","article-title":"Solubility of cyclomaltooligosaccharides (cyclodextrins) in H2O and D2O: A comparative study","volume":"341","author":"Sabadini","year":"2006","journal-title":"Carbohydr. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1002\/jps.23077","article-title":"Cyclodextrins as functional excipients: Methods to enhance complexation efficiency","volume":"101","author":"Loftsson","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_24","first-page":"175","article-title":"Chapter 3. Complexation","volume":"Volume 3","author":"Riley","year":"1991","journal-title":"Takero Higuchi: A Memorial Tribute"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12385","DOI":"10.1021\/acs.chemrev.7b00259","article-title":"How Water\u2019s Properties Are Encoded in Its Molecular Structure and Energies","volume":"117","author":"Brini","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10694","DOI":"10.1021\/acs.chemrev.6b00765","article-title":"Water Dynamics in the Hydration Shells of Biomolecules","volume":"117","author":"Laage","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1021\/acs.accounts.8b00258","article-title":"Surface Water as a Mediator and Reporter of Adhesion at Aqueous Interfaces","volume":"51","author":"Jarisz","year":"2018","journal-title":"Acc. Chem. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ijpharm.2007.08.049","article-title":"Physicochemical properties of water and its effect on drug delivery\u2014A commentary","volume":"354","author":"Loftsson","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_29","unstructured":"Chaplin, M. (2023, February 10). Water Structure and Science. Available online: http:\/\/www1.lsbu.ac.uk\/water\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"22867","DOI":"10.1021\/jp309744s","article-title":"Simulated Structure and Nonlinear Vibrational Spectra of Water Next to Hydrophobic and Hydrophilic Solid Surfaces","volume":"116","author":"Roy","year":"2012","journal-title":"J. Phys. Chem. C"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1146\/annurev-chembioeng-120919-114657","article-title":"Water Structure and Properties at Hydrophilic and Hydrophobic Surfaces","volume":"11","author":"Monroe","year":"2020","journal-title":"Annu. Rev. Chem. Biomol. Eng."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1002\/cbdv.200900112","article-title":"In silico Prediction of Human Oral Absorption Based on QSAR Analyses of PAMPA Permeability","volume":"6","author":"Akamatsu","year":"2009","journal-title":"Chem. Biodivers."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1002\/jps.21762","article-title":"Analysis of unstirred water layer in in vitro permeability experiments","volume":"98","author":"Korjamo","year":"2009","journal-title":"J. Pharm. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1111\/j.2042-7158.2011.01279.x","article-title":"Pharmaceutical applications of cyclodextrins: Effects on drug permeation through biological membranes","volume":"63","author":"Loftsson","year":"2011","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_35","first-page":"363","article-title":"Drug permeation through biomembranes: Cyclodextrins and the unstirred water layer","volume":"67","author":"Loftsson","year":"2012","journal-title":"Pharmazie"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25655","DOI":"10.1021\/acsomega.0c02760","article-title":"Molecular View into the Cyclodextrin Cavity: Structure and Hydration","volume":"5","author":"Sandilya","year":"2020","journal-title":"ACS Omega"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Soe, H.M.S.H., Maw, P.D., Loftsson, T., and Jansook, P. (2022). Current Overview of Cyclodextrin-Based Nanocarriers for Enhanced Antifungal Delivery. Pharmaceutics, 15.","DOI":"10.3390\/ph15121447"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1021\/cr970022c","article-title":"Introduction and General Overview of Cyclodextrin Chemistry","volume":"98","author":"Szejtli","year":"1998","journal-title":"Chem. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/BF01053637","article-title":"Aggregation of cyclodextrins: An explanation of the abnormal solubility of \u03b2-cyclodextrin","volume":"13","author":"Coleman","year":"1992","journal-title":"J. Incl. Phenom. Mol. Recognit. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1002\/jrs.5372","article-title":"Hydration properties and water structure in aqueous solutions of native and modified cyclodextrins by UV Raman and Brillouin scattering","volume":"49","author":"Bottari","year":"2018","journal-title":"J. Raman Spectrosc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/nrd1576","article-title":"Cyclodextrin-based pharmaceutics: Past, present and future","volume":"3","author":"Davis","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1016\/j.xphs.2016.04.034","article-title":"\u201cBack to the Future\u201d: A New Look at Hydroxypropyl Beta-Cyclodextrins","volume":"105","author":"Malanga","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1016\/j.xphs.2016.01.019","article-title":"Self-assembly of cyclodextrins and their complexes in aqueous solutions","volume":"105","author":"Ryzhakov","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ijpharm.2019.02.004","article-title":"Self-association of cyclodextrins and cyclodextrin complexes in aqueous solutions","volume":"560","author":"Loftsson","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.micron.2007.06.017","article-title":"Cyclodextrin-based aggregates and characterization by microscopy","volume":"39","author":"He","year":"2008","journal-title":"Micron"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Fourmentin, S., Crini, G., and Lichtfouse, E. (2018). Cyclodextrin Fundamentals, Reactivity and Analysis, Springer Nature Switzerland AG.","DOI":"10.1007\/978-3-319-76159-6"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1023\/A:1023065823358","article-title":"The aggregation of cyclodextrins as studied by photon correlation spectroscopy","volume":"44","author":"Rodriguez","year":"2002","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ijpharm.2009.11.035","article-title":"Self-assembled cyclodextrin aggregates and nanoparticles","volume":"387","author":"Messner","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1246\/bcsj.56.3556","article-title":"Viscosity B-cofficients, apparent molar volumes, and activity coefficients for \u03b1- and \u03b3-cyclodextrins in aqueous solutions","volume":"56","author":"Miyajima","year":"1983","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1021\/la052878f","article-title":"Self-assembly of \u03b2-cyclodextrin in water. Part 1: Cryo-TEM and dynamic and static light scattering","volume":"22","author":"Bonini","year":"2006","journal-title":"Langmuir"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/star.19930450508","article-title":"Properties and Structure of Aqueous Solutions of Hydroxypropyl-beta-Cyclodextrin","volume":"45","year":"1993","journal-title":"Starch-St\u00e4rke"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jcis.2006.05.065","article-title":"Micrometer-sized rodlike structure formed by the secondary assembly of cyclodextrin nanotube","volume":"302","author":"Wu","year":"2006","journal-title":"J. Colloid Interface Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1034\/j.1600-0420.2002.800205.x","article-title":"Aqueous eye drops containing drug\/cyclodextrin nanoparticles deliver therapeutic drug concentrations to both anterior and posterior segment","volume":"80","author":"Loftsson","year":"2021","journal-title":"Acta Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.xphs.2020.10.026","article-title":"Cyclodextrins in Parenteral Formulations","volume":"110","author":"Loftsson","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1002\/jps.10226","article-title":"Self-association and cyclodextrin solubilization of drugs","volume":"91","author":"Loftsson","year":"2002","journal-title":"J. Pharm. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1023\/A:1023079322024","article-title":"Self Association and Cyclodextrin Solubilization of NSAIDs","volume":"44","author":"Magnusdottir","year":"2002","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.ijpharm.2017.05.024","article-title":"Soluble 1:1 complexes and insoluble 3:2 complexes\u2014Understanding the phase-solubility diagram of hydrocortisone and \u03b3-cyclodextrin","volume":"531","author":"Madsen","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1007\/s00289-017-2203-z","article-title":"Influence of hydrophilic polymers addition into cinnarizine-\u03b2-cyclodextrin complexes on drug solubility, drug liberation behaviour and drug permeability","volume":"75","author":"Singh","year":"2018","journal-title":"Polym. Bull."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.ijpharm.2017.02.037","article-title":"A study of the aggregation of cyclodextrins: Determination of the critical aggregation concentration, size of aggregates and thermodynamics using isodesmic and K2\u2013K models","volume":"521","author":"Do","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ijpharm.2013.06.058","article-title":"A permeation method for detection of self-aggregation of doxorubicin in aqueous environment","volume":"454","author":"Fulop","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s10847-006-9247-2","article-title":"The complexation efficiency","volume":"57","author":"Loftsson","year":"2007","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e17776\/1","DOI":"10.1590\/s2175-97902019000117776","article-title":"Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles","volume":"55","author":"Rodrigues","year":"2019","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ijpharm.2005.05.042","article-title":"Evaluation of cyclodextrin solubilization of drugs","volume":"302","author":"Loftsson","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/jps.20047","article-title":"Self-Association of Cyclodextrins and Cyclodextrin Complexes","volume":"93","author":"Loftsson","year":"2004","journal-title":"J. Pharm. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1081\/DDC-120016689","article-title":"Examination of 19F-NMR as a Tool for Investigation of Drug-Cyclodextrin Complexes","volume":"29","author":"Loftsson","year":"2003","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1248\/cpb.26.3477","article-title":"Determination of the stability constants for inclusion complexes of cyclodextrins with various drug molecules by high performance liquid chromatography","volume":"26","author":"Uekama","year":"1978","journal-title":"Chem. Pharm. Bull."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S0731-7085(98)00139-3","article-title":"Characterization of the complexation of diflunisal with hydroxypropyl-\u03b2-cyclodextrin","volume":"19","author":"Ugwu","year":"1999","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0928-0987(98)00035-9","article-title":"Studies on the interaction of diflunisal ion with cyclodextrins using ion-selective electrode potentiometry","volume":"7","author":"Sideris","year":"1999","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"35196","DOI":"10.1021\/acsomega.1c05420","article-title":"Polymers as Versatile Players in the Stabilization, Capping, and Design of Inorganic Nanostructures","volume":"6","author":"Aguilar","year":"2021","journal-title":"ACS Omega"},{"key":"ref_70","unstructured":"Shvets, A. (2020). Theory of Colloidal Stabilization by Unattached Polymers, Cornell University Library."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cis.2008.10.001","article-title":"Polymer\u2013vesicle association","volume":"147\u2013148","author":"Antunes","year":"2009","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.cej.2010.07.035","article-title":"Enhanced solubilization of phenanthrene in Triton X-100 solutions by the addition of small amounts of chitosan","volume":"163","author":"Chatterjee","year":"2010","journal-title":"Chem. Eng. J."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Attwood, D., and Florence, A.T. (1983). Surfactant Systems. Their Chemistry, Pharmacy and Biology, Springer.","DOI":"10.1007\/978-94-009-5775-6"},{"key":"ref_74","unstructured":"Goddard, E.D., and Ananthapadmanabhan, K.P. (1992). Interactions of Surfactants with Polymers and Proteins, CRC."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"118712","DOI":"10.1016\/j.carbpol.2021.118712","article-title":"In silico formulation prediction of drug\/cyclodextrin\/polymer ternary complexes by machine learning and molecular modeling techniques","volume":"275","author":"Li","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Chadha, R., Bala, M., Goyal, P., Chadha, K., and Karan, M. (2015). Role of Polymers in Ternary Drug Cyclodextrin Complexes, Scrivener Publishing LLC.","DOI":"10.1002\/9781119041450.ch12"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0378-5173(94)90155-4","article-title":"The effect of water-soluble polymers on drug-cyclodextrin complexation","volume":"110","author":"Loftsson","year":"1994","journal-title":"Int. J. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3109\/03639049609069348","article-title":"The influence of water-soluble polymers and pH on hydroxylpropyl-\u03b2-cyclodextrin complexation of drugs","volume":"22","author":"Loftsson","year":"1996","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2022038870","article-title":"Cyclodextrin-Based Supramolecular Ternary Complexes: Emerging Role of Ternary Agents on Drug Solubility, Stability, and Bioavailability","volume":"39","author":"Suvarna","year":"2022","journal-title":"Crit. Rev. Ther. Drug Carr. Syst."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5974","DOI":"10.1021\/cr9000622","article-title":"CD-based polymeric rotaxanes","volume":"109","author":"Harada","year":"2009","journal-title":"Chem. Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0378-5173(97)00371-2","article-title":"The effect of water-soluble polymers on the aqueous solubility and complexing abilities of \u03b2-cyclodextrin","volume":"163","author":"Loftsson","year":"1998","journal-title":"Int. J. Pharm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1023\/A:1008094702632","article-title":"Interaction of hydroxy acids with beta-cyclodextrin","volume":"33","author":"Fenyvesi","year":"1999","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1520-6017(200001)89:1<1::AID-JPS1>3.0.CO;2-W","article-title":"Drug\/cyclodextrin\/hydroxy acid multicomponent systems. Properties and pharmaceutical applications","volume":"89","author":"Redenti","year":"2000","journal-title":"J. Pharm. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0378-5173(03)00334-X","article-title":"The effects of organic salts on the cyclodextrin solubilization of drugs","volume":"262","author":"Loftsson","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_85","first-page":"681","article-title":"Complex formation","volume":"Volume 1","author":"Allen","year":"2013","journal-title":"Remington, the Science and Practice of Pharmacy"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1016\/j.xphs.2022.04.015","article-title":"Cyclodextrins and Drug Membrane Permeation: Thermodynamic Considerations","volume":"111","author":"Sripetch","year":"2022","journal-title":"J. Pharm. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"113711","DOI":"10.1016\/j.jpba.2020.113711","article-title":"Corona Charged Aerosol Detector in studying retention and \u03b2-cyclodextrin complex stability using RP-HPLC","volume":"193","author":"Djajic","year":"2021","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/jphp.12427","article-title":"Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug\/cyclodextrin complexes","volume":"68","author":"Loftsson","year":"2016","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1177\/0192623307310945","article-title":"Cyclodextrins","volume":"36","author":"Stella","year":"2008","journal-title":"Toxicol. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11095-019-2701-9","article-title":"Mucins are Involved in the Intestinal Permeation of Lipophilic Drugs in the Proximal Region of Rat Small Intestine","volume":"36","author":"Miyazaki","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nrgastro.2013.35","article-title":"The gastrointestinal mucus system in health and disease","volume":"10","author":"Johansson","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ijpharm.2007.04.029","article-title":"Effect of the unstirred water layer on permeability enhancement by hydrophilic cyclodextrins","volume":"342","author":"Brewster","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1002\/jps.20992","article-title":"Effects of cyclodextrins on drug delivery through biological membranes","volume":"96","author":"Loftsson","year":"2007","journal-title":"J. Pharm. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ejps.2017.12.014","article-title":"The effect of 2-hydroxypropyl-\u03b2-cyclodextrin on the intestinal permeation through mucus","volume":"114","author":"Stappaerts","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"120494","DOI":"10.1016\/j.ijpharm.2021.120494","article-title":"In vitro-in vivo correlation in the effect of cyclodextrin on oral absorption of poorly soluble drugs","volume":"600","author":"Aihara","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ejpb.2022.08.009","article-title":"Modelling drug diffusion through unstirred water layers allows real-time quantification of free\/loaded drug fractions and release kinetics from colloidal-based formulations","volume":"178","author":"Tzanova","year":"2022","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jconrel.2021.05.020","article-title":"Nasal biocompatible powder of Geraniol oil complexed with cyclodextrins for neurodegenerative diseases: Physicochemical characterization and in vivo evidences of nose to brain delivery","volume":"335","author":"Truzzi","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ijpharm.2013.05.013","article-title":"Drug precipitation inhibitors in supersaturable formulations","volume":"453","author":"Xu","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"6323","DOI":"10.1021\/acs.cgd.2c00787","article-title":"Solution Stability of Pharmaceutical Cocrystals","volume":"22","author":"Alvani","year":"2022","journal-title":"Cryst. Growth Des."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/jphp.12927","article-title":"Approaches to increase mechanistic understanding and aid in the selection of precipitation inhibitors for supersaturating formulations\u2014A PEARRL review","volume":"71","author":"Price","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2006.07.011","article-title":"A century of dissolution research: From Noyes and Whitney to the Biopharmaceutics Classification System","volume":"321","author":"Dokoumetzidis","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1248\/cpb.55.1466","article-title":"Improvement of Dissolution Properties of a New Helicobacter pylori Eradicating Agent (TG44) by Inclusion Complexation with \u03b2-Cyclodextrin","volume":"55","author":"Anzai","year":"2007","journal-title":"Chem. Pharm. Bull."},{"key":"ref_103","first-page":"25","article-title":"Preparation of solid drug\/cyclodextrin complexes of acidic and basic drugs","volume":"59","author":"Loftsson","year":"2004","journal-title":"Pharmazie"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/jps.2600800421","article-title":"Oversaturated Solutions of Drug in Hydroxypropylcyclodextrins: Parenteral Preparation of Pancratistatin","volume":"80","author":"Davignon","year":"1991","journal-title":"J. Pharm. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/jps.22750","article-title":"Supersaturating Drug Delivery Systems: Fast is Not Necessarily Good Enough","volume":"101","author":"Augustijns","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1016\/j.xphs.2021.07.002","article-title":"Stabilization of the Metastable \u03b1\u2013Form of Indomethacin Induced by the Addition of 2-Hydroxypropyl-\u03b2-Cyclodextrin, Causing Supersaturation (Spring) and Its Sustaining Deployment (Parachute)","volume":"110","author":"Shimizu","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ejps.2008.02.007","article-title":"Comparative interaction of 2-hydroxypropyl-\u03b2-cyclodextrin and sulfobutylether-\u03b2-cyclodextrin with itraconazole: Phase-solubility behavior and stabilization of supersaturated drug solutions","volume":"34","author":"Brewster","year":"2008","journal-title":"Eur. J. Pharm. Sci."}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/16\/6\/2223\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:51:42Z","timestamp":1760122302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/16\/6\/2223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,10]]},"references-count":107,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ma16062223"],"URL":"https:\/\/doi.org\/10.3390\/ma16062223","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,10]]}}}