{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:12:30Z","timestamp":1787958750598,"version":"build-2784847793"},"reference-count":72,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"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>Carvedilol is a poorly water-soluble drug employed to treat chronic heart failure. In this study, we synthesize new carvedilol-etched halloysite nanotubes (HNTs) composites to enhance solubility and dissolution rate. The simple and feasible impregnation method is used for carvedilol loading (30\u201337% weight). Both the etched HNTs (acidic HCl and H2SO4 and alkaline NaOH treatments) and the carvedilol-loaded samples are characterized by various techniques (XRPD, FT-IR, solid-state NMR, SEM, TEM, DSC, and specific surface area). The etching and loading processes do not induce structural changes. The drug and carrier particles are in intimate contact and their morphology is preserved, as demonstrated by TEM images. The 27Al and 13C solid-state NMR and FT-IR findings show that carvedilol interactions involve the external siloxane surface, especially the aliphatic carbons, the functional groups, and, by inductive effect, the adjacent aromatic carbons. All the carvedilol\u2013halloysite composites display enhanced dissolution rate, wettability, and solubility, as compared to carvedilol. The best performances are obtained for the carvedilol\u2013halloysite system based on HNTs etched with HCl 8M, which exhibits the highest value of specific surface area (91 m2 g\u22121). The composites make the drug dissolution independent of the environmental conditions of the gastrointestinal tract and its absorption less variable, more predictable, and independent from the pH of the medium.<\/jats:p>","DOI":"10.3390\/molecules28083405","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T02:09:21Z","timestamp":1681351761000},"page":"3405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synthesis and Characterization of Carvedilol-Etched Halloysite Nanotubes Composites with Enhanced Drug Solubility and Dissolution Rate"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1408-8846","authenticated-orcid":false,"given":"Lauretta","family":"Maggi","sequence":"first","affiliation":[{"name":"Department of Drug Sciences, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Urru","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Physical Chemistry Section & C.S.G.I. (Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase), University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Friuli","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5834-8646","authenticated-orcid":false,"given":"Chiara","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Department of Materials Science, University of Milano-Bicocca, Via Cozzi 55, 20125 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora Maria","family":"Conti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Physical Chemistry Section & C.S.G.I. (Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase), University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1958-2998","authenticated-orcid":false,"given":"Giovanna","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Physical Chemistry Section & C.S.G.I. (Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase), University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1064-7196","authenticated-orcid":false,"given":"Doretta","family":"Capsoni","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Physical Chemistry Section & C.S.G.I. (Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase), University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1021\/cg801039j","article-title":"Solubility Advantage of Pharmaceutical Cocrystals","volume":"9","author":"Good","year":"2009","journal-title":"Cryst. Growth Des."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ijcard.2009.09.543","article-title":"The Relationship of Autonomic Imbalance, Heart Rate Variability and Cardiovascular Disease Risk Factors","volume":"141","author":"Thayer","year":"2010","journal-title":"Int. J. Cardiol."},{"key":"ref_3","first-page":"23","article-title":"Various Techniques for Solubility Enhancement: An Overview","volume":"5","author":"Kumar","year":"2016","journal-title":"Pharma Innov."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hosseini, M.W. (2009). Molecular Networks, Springer. Structure and Bonding.","DOI":"10.1007\/978-3-642-01367-6"},{"key":"ref_5","first-page":"37","article-title":"Polymorphism of Pharmaceutical Molecules: Perspectives on Nucleation","volume":"4","author":"Lu","year":"2010","journal-title":"Front. Chem. Sci. Eng."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1002\/jps.20924","article-title":"Solvent Influences on Metastable Polymorph Lifetimes: Real-Time Interconversions Using Energy Dispersive X-Ray Diffractometry","volume":"96","author":"DeMatos","year":"2007","journal-title":"J. Pharm. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1021\/mp0700054","article-title":"Screening for Pharmaceutical Cocrystal Hydrates via Neat and Liquid-Assisted Grinding","volume":"4","author":"Karki","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/jps.20302","article-title":"Trends in Solubility of Polymorphs","volume":"94","author":"Pudipeddi","year":"2005","journal-title":"J. Pharm. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1021\/cg400331h","article-title":"Molecular Salts of Anesthetic Lidocaine with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study","volume":"13","author":"Braga","year":"2013","journal-title":"Cryst. Growth Des."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6035","DOI":"10.1039\/c2ce25846c","article-title":"Perphenazine\u2013Fumaric Acid Salts with Improved Solubility: Preparation, Physico-Chemical Characterization and in Vitro Dissolution","volume":"14","author":"Bruni","year":"2012","journal-title":"CrystEngComm"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1039\/B512626F","article-title":"Screening for Crystalline Salts via Mechanochemistry","volume":"1","author":"Trask","year":"2006","journal-title":"Chem. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3976","DOI":"10.1021\/cg9001187","article-title":"Understanding and Predicting the Effect of Cocrystal Components and PH on Cocrystal Solubility","volume":"9","author":"Bethune","year":"2009","journal-title":"Cryst. Growth Des."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1002\/jps.23721","article-title":"Preparation and Physicochemical Characterization of Acyclovir Cocrystals with Improved Dissolution Properties","volume":"102","author":"Bruni","year":"2013","journal-title":"J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1039\/b616399h","article-title":"Cocrystal Architecture and Properties: Design and Building of Chiral and Racemic Structures by Solid\u2013Solid Reactions","volume":"136","author":"Jones","year":"2007","journal-title":"Faraday Discuss."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"118639","DOI":"10.1016\/j.ijpharm.2019.118639","article-title":"Complex Methodology for Rational Design of Apremilast-Benzoic Acid Co-Crystallization Process","volume":"570","author":"Ondo","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.ijpharm.2017.08.087","article-title":"Drug Solubilization by Complexation","volume":"531","author":"Loftsson","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"437","DOI":"10.3389\/fbioe.2020.00437","article-title":"Strategies to Obtain Encapsulation and Controlled Release of Small Hydrophilic Molecules","volume":"8","author":"Li","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tran, T.T.D., and Tran, P.H.L. (2019). Nanoconjugation and Encapsulation Strategies for Improving Drug Delivery and Therapeutic Efficacy of Poorly Water-Soluble Drugs. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11070325"},{"key":"ref_19","first-page":"3333","article-title":"Silymarin-Loaded Solid Nanoparticles Provide Excellent Hepatic Protection: Physicochemical Characterization and in Vivo Evaluation","volume":"8","author":"Yang","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Massaro, M., Colletti, C.G., Lazzara, G., and Riela, S. (2018). The Use of Some Clay Minerals as Natural Resources for Drug Carrier Applications. J. Funct. Biomater., 9.","DOI":"10.3390\/jfb9040058"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1039\/c3tb20059k","article-title":"Halloysite Clay Nanotubes as a Ceramic \u201cSkeleton\u201d for Functional Biopolymer Composites with Sustained Drug Release","volume":"1","author":"Abdullayev","year":"2013","journal-title":"J. Mater. Chem. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1039\/C5EN00149H","article-title":"Recent Advance of Halloysite Nanotubes Derived Composites in Water Treatment","volume":"3","author":"Yu","year":"2015","journal-title":"Environ. Sci. Nano"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00604-018-2908-1","article-title":"Halloysite Nanotubes in Analytical Sciences and in Drug Delivery: A Review","volume":"185","author":"Fizir","year":"2018","journal-title":"Mikrochim Acta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.clay.2015.05.001","article-title":"Properties and Applications of Halloysite Nanotubes: Recent Research Advances and Future Prospects","volume":"112\u2013113","author":"Yuan","year":"2015","journal-title":"Appl. Clay Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.cis.2013.10.006","article-title":"Clay Nanotube Encapsulation for Functional Biocomposites","volume":"207","author":"Lvov","year":"2014","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106303","DOI":"10.1016\/j.clay.2021.106303","article-title":"The Relation between Nanotube Diameter, Length and Surface Area and Pore Volume of Multi-Walled Spiral Halloysite Nanotubes: A Theoretical Study","volume":"215","author":"Liu","year":"2021","journal-title":"Appl. Clay Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.micromeso.2015.08.002","article-title":"Physicochemical Characterization of Organosilylated Halloysite Clay Nanotubes","volume":"219","author":"Peixoto","year":"2016","journal-title":"Microporous Mesoporous Mater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"26578","DOI":"10.1021\/acsami.6b09074","article-title":"Enhanced Therapeutic Efficacy of Doxorubicin for Breast Cancer Using Chitosan Oligosaccharide-Modified Halloysite Nanotubes","volume":"8","author":"Yang","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7216","DOI":"10.1021\/nn302328x","article-title":"Enlargement of Halloysite Clay Nanotube Lumen by Selective Etching of Aluminum Oxide","volume":"6","author":"Abdullayev","year":"2012","journal-title":"ACS Nano"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"065705","DOI":"10.1088\/0957-4484\/23\/6\/065705","article-title":"The Stability of Halloysite Nanotubes in Acidic and Alkaline Aqueous Suspensions","volume":"23","author":"White","year":"2012","journal-title":"Nanotechnology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10973-011-1522-9","article-title":"Study of Urea Intercalation into Halloysite by Thermoanalytical and Spectroscopic Techniques","volume":"105","author":"Kurdi","year":"2011","journal-title":"J. Therm. Anal. Calorim."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.jcis.2009.06.058","article-title":"Dehydrated Halloysite Intercalated Mechanochemically with Urea: Thermal Behavior and Structural Aspects","volume":"338","author":"Nicolini","year":"2009","journal-title":"J. Colloid Interface Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1021\/ja210258y","article-title":"Selective Modification of Halloysite Lumen with Octadecylphosphonic Acid: New Inorganic Tubular Micelle","volume":"134","author":"Yah","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12134","DOI":"10.1021\/ja303340f","article-title":"Biomimetic Dopamine Derivative for Selective Polymer Modification of Halloysite Nanotube Lumen","volume":"134","author":"Yah","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.colsurfb.2015.07.021","article-title":"In-Vitro Assessment of Cytotoxicity of Halloysite Nanotubes against HepG2, HCT116 and Human Peripheral Blood Lymphocytes","volume":"135","author":"Ahmed","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Capsoni, D., Lucini, P., Conti, D.M., Bianchi, M., Maraschi, F., De Felice, B., Bruni, G., Abdolrahimi, M., Peddis, D., and Parolini, M. (2022). Fe3O4-Halloysite Nanotube Composites as Sustainable Adsorbents: Efficiency in Ofloxacin Removal from Polluted Waters and Ecotoxicity. Nanomaterials, 12.","DOI":"10.3390\/nano12234330"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1056\/NEJM199812103392407","article-title":"Carvedilol","volume":"339","author":"Frishman","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1056\/NEJM199605233342101","article-title":"The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart Failure. U.S. Carvedilol Heart Failure Study Group","volume":"334","author":"Packer","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1208\/s12249-008-9055-7","article-title":"Carvedilol: Solubilization and Cyclodextrin Complexation: A Technical Note","volume":"9","author":"Loftsson","year":"2008","journal-title":"Aaps Pharmscitech"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sip, S., Paczkowska-Walendowska, M., Rosiak, N., Miklaszewski, A., Graba\u0144ska-Marty\u0144ska, K., Samarzewska, K., and Cielecka-Piontek, J. (2021). Chitosan as Valuable Excipient for Oral and Topical Carvedilol Delivery Systems. Pharmaceuticals, 14.","DOI":"10.3390\/ph14080712"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/B978-0-12-407691-4.00004-6","article-title":"Chapter Four\u2014Carvedilol","volume":"Volume 38","author":"Brittain","year":"2013","journal-title":"Profiles of Drug Substances, Excipients and Related Methodology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"111622","DOI":"10.1016\/j.molliq.2019.111622","article-title":"Equilibrium Solubility and Solute-Solvent Interactions of Carvedilol (Form I) in Twelve Mono Solvents and Its Application for Supercritical Antisolvent Precipitation","volume":"294","author":"Ha","year":"2019","journal-title":"J. Mol. Liq."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/2008-2231-20-93","article-title":"Chitosan and Chitosan Chlorhydrate Based Various Approaches for Enhancement of Dissolution Rate of Carvedilol","volume":"20","author":"Shete","year":"2012","journal-title":"Daru J. Fac. Pharm. Tehran Univ. Med Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1208\/s12249-011-9750-7","article-title":"Fabrication of Carvedilol Nanosuspensions through the Anti-Solvent Precipitation-Ultrasonication Method for the Improvement of Dissolution Rate and Oral Bioavailability","volume":"13","author":"Liu","year":"2012","journal-title":"Aaps Pharmscitech"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/s12272-013-0023-8","article-title":"Adipose Tissue Macrophages in the Development of Obesity-Induced Inflammation, Insulin Resistance and Type 2 Diabetes","volume":"36","author":"Lee","year":"2013","journal-title":"Arch. Pharm. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s43094-020-00083-5","article-title":"Solubility Enhancement of Carvedilol Using Drug\u2013Drug Cocrystallization with Hydrochlorothiazide","volume":"6","author":"Eesam","year":"2020","journal-title":"Future J. Pharm. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0378-5173(02)00274-0","article-title":"Characterisation of Halloysite for Use as a Microtubular Drug Delivery System","volume":"243","author":"Levis","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4547","DOI":"10.1007\/s11696-020-01263-6","article-title":"Characterization Studies of Heat-Treated Halloysite Nanotubes","volume":"74","author":"Aytekin","year":"2020","journal-title":"Chem. Pap."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1016\/j.progpolymsci.2013.05.009","article-title":"Functional Polymer\u2013Clay Nanotube Composites with Sustained Release of Chemical Agents","volume":"38","author":"Lvov","year":"2013","journal-title":"Prog. Polym. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jhazmat.2016.01.081","article-title":"Cr(VI) Reduction and Immobilization by Novel Carbonaceous Modified Magnetic Fe3O4\/Halloysite Nanohybrid","volume":"309","author":"Tian","year":"2016","journal-title":"J. Hazard. Mater."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.cej.2011.02.031","article-title":"Magnetic Halloysite Nanotubes\/Iron Oxide Composites for the Adsorption of Dyes","volume":"168","author":"Xie","year":"2011","journal-title":"Chem. Eng. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1039\/C3CE42403K","article-title":"An Insight into Carvedilol Solid Forms: Effect of Supramolecular Interactions on the Dissolution Profiles","volume":"16","author":"Prado","year":"2014","journal-title":"CrystEngComm"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.apsusc.2014.12.158","article-title":"Amylose\u2013Halloysite\u2013TiO2 Composites: Preparation, Characterization and Photodegradation","volume":"329","author":"Zheng","year":"2015","journal-title":"Appl. Surf. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1007\/s00604-015-1491-y","article-title":"A Composite Prepared from Halloysite Nanotubes and Magnetite (Fe3O4) as a New Magnetic Sorbent for the Preconcentration of Cadmium(II) Prior to Its Determination by Flame Atomic Absorption Spectrometry","volume":"182","author":"Amjadi","year":"2015","journal-title":"Microchim. Acta"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.saa.2010.08.039","article-title":"Infrared and Infrared Emission Spectroscopic Study of Typical Chinese Kaolinite and Halloysite","volume":"77","author":"Cheng","year":"2010","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1039\/c1ay05247k","article-title":"Quantitative Determination and Validation of Carvedilol in Pharmaceuticals Using Quantitative Nuclear Magnetic Resonance Spectroscopy","volume":"3","author":"Gadape","year":"2011","journal-title":"Anal. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0731-7085(03)00576-4","article-title":"Preparation and Study the 1:2 Inclusion Complex of Carvedilol with \u03b2-Cyclodextrin","volume":"34","author":"Wen","year":"2004","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/mrc.2742","article-title":"1H and 13C NMR Characteristics of \u03b2-Blockers","volume":"49","author":"Pisklak","year":"2011","journal-title":"Magn. Reson. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ravikumar, A.A., Kulkarni, P.K., Osmani, R.A.M., Hani, U., Ghazwani, M., Fatease, A.A., Alamri, A.H., and Gowda, D.V. (2022). Carvedilol Precipitation Inhibition by the Incorporation of Polymeric Precipitation Inhibitors Using a Stable Amorphous Solid Dispersion Approach: Formulation, Characterization, and In Vitro In Vivo Evaluation. Polymers, 14.","DOI":"10.3390\/polym14224977"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.xphs.2018.11.033","article-title":"Enhancing the Pharmaceutical Behavior of Nateglinide by Cocrystallization: Physicochemical Assessment of Cocrystal Formation and Informed Use of Differential Scanning Calorimetry for Its Quantitative Characterization","volume":"108","author":"Bruni","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1007\/s10973-019-09197-2","article-title":"Probenecid and Benzamide: Cocrystal Prepared by a Green Method and Its Physico-Chemical and Pharmaceutical Characterization","volume":"140","author":"Bruni","year":"2020","journal-title":"J. Therm. Anal. Calorim."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"106723","DOI":"10.1016\/j.clay.2022.106723","article-title":"Zaltoprofen-Layered Double Hydroxide Hybrids to Enhance Zaltoprofen Solubility and Dissolution Rate","volume":"231","author":"Maggi","year":"2023","journal-title":"Appl. Clay Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"997","DOI":"10.2138\/am-2017-5935","article-title":"Transformation of Halloysite and Kaolinite into Beidellite under Hydrothermal Condition","volume":"102","author":"He","year":"2017","journal-title":"Am. Mineral."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"23451","DOI":"10.1021\/jp403022j","article-title":"Local versus Average Structure in LaSrAl3O7: A NMR and DFT Investigation","volume":"117","author":"Ferrara","year":"2013","journal-title":"J. Phys. Chem. C"},{"key":"ref_65","unstructured":"MacKenzie, K., and Smith, M.E. (2012). Multinuclear Solid-State Nuclear Magnetic Resonance of Inorganic Materials, Elsevier. [1st ed.]."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"012011","DOI":"10.1088\/1757-899X\/265\/1\/012011","article-title":"Preparation of a Novel Breviscapine-Loaded Halloysite Nanotubes Complex for Controlled Release of Breviscapine","volume":"265","author":"Gao","year":"2017","journal-title":"IOP Conf. Ser. Mater. Sci. Eng."},{"key":"ref_67","unstructured":"(2017). The United States Pharmacopoeia (USP40-NF35), United States Pharmacopeial Convention, Inc."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.colsurfb.2013.08.036","article-title":"Adsorption and Release of Ofloxacin from Acid- and Heat-Treated Halloysite","volume":"113","author":"Wang","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Surya, I., Waesateh, K., Masa, A., and Hayeemasae, N. (2021). Selectively Etched Halloysite Nanotubes as Performance Booster of Epoxidized Natural Rubber Composites. Polymers, 13.","DOI":"10.3390\/polym13203536"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.apsusc.2013.09.057","article-title":"Alkali Activation of Halloysite for Adsorption and Release of Ofloxacin","volume":"287","author":"Wang","year":"2013","journal-title":"Appl. Surf. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5663","DOI":"10.1016\/j.apsusc.2011.01.071","article-title":"Functional and Unmodified MWNTs for Delivery of the Water-Insoluble Drug Carvedilol\u2014A Drug-Loading Mechanism","volume":"257","author":"Li","year":"2011","journal-title":"Appl. Surf. Sci."},{"key":"ref_72","unstructured":"(2017). The United States Pharmacopeia (USP40-NF35), United States Pharmacopeial Convention, Inc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/8\/3405\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:14:46Z","timestamp":1760123686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/8\/3405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,12]]},"references-count":72,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["molecules28083405"],"URL":"https:\/\/doi.org\/10.3390\/molecules28083405","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,12]]}}}