{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:43:06Z","timestamp":1792806186669,"version":"4.5.0"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia through two Grant Agreements with the University of Belgrade\u2019s Faculty of Pharmacy","award":["451\u201303-65\/2024\u201303\/200161"],"award-info":[{"award-number":["451\u201303-65\/2024\u201303\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia through two Grant Agreements with the University of Belgrade\u2019s Faculty of Pharmacy","award":["451\u201303-66\/2024\u201303\/200161"],"award-info":[{"award-number":["451\u201303-66\/2024\u201303\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Selective laser sintering (SLS) is one of the most promising 3D printing techniques for pharmaceutical applications as it offers numerous advantages, such as suitability to work with already approved pharmaceutical excipients, the elimination of solvents, and the ability to produce fast-dissolving, porous dosage forms with high drug loading. When the powder mixture is exposed to elevated temperatures during SLS printing, the active ingredients can be converted from the crystalline to the amorphous state, which can be used as a strategy to improve the dissolution rate and bioavailability of poorly soluble drugs. This study investigates the potential application of SLS 3D printing for the fabrication of tablets containing the poorly soluble drug carvedilol with the aim of improving the dissolution rate of the drug by forming an amorphous form through the printing process. Methods: Using SLS 3D printing, eight tablet formulations were produced using two different powder mixtures and four combinations of experimental conditions, followed by physicochemical characterization and dissolution testing. Results: Physicochemical characterization revealed that at least partial amorphization of carvedilol occurred during the printing process. Although variations in process parameters were minimal, higher temperatures in combination with lower laser speeds appeared to facilitate a greater degree of amorphization. Ultimately, the partial conversion to the amorphous form significantly improved the dissolution of carvedilol compared to its pure crystalline form. Conclusions: Obtained results suggest that the SLS 3D printing technique can be effectively used to convert poorly water-soluble drugs to their amorphous state, thereby improving solubility and bioavailability.<\/jats:p>","DOI":"10.3390\/pharmaceutics17010006","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T09:48:58Z","timestamp":1735033738000},"page":"6","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Selective Laser Sintering 3D Printing of Carvedilol Tablets: Enhancing Dissolution Through Amorphization"],"prefix":"10.3390","volume":"17","author":[{"given":"Nikola","family":"Pe\u0161i\u0107","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branka","family":"Ivkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-9609","authenticated-orcid":false,"given":"Tanja","family":"Barud\u017eija","sequence":"additional","affiliation":[{"name":"Vin\u010da Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovi\u0107a Alasa 12\u201314, 11351 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branka","family":"Gruji\u0107","sequence":"additional","affiliation":[{"name":"Galenika a.d., Batajni\u010dki drum bb., 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1101-6174","authenticated-orcid":false,"given":"Svetlana","family":"Ibri\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djordje","family":"Medarevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119594","DOI":"10.1016\/j.ijpharm.2020.119594","article-title":"3D Printing: Principles and Pharmaceutical Applications of Selective Laser Sintering","volume":"586","author":"Awad","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Medarevi\u0107, D., Krsti\u0107, M., and Ibri\u0107, S. (2024). Fundamentals of 3D Printing of Pharmaceuticals. From Current to Future Trends in Pharmaceutical Technology, Elsevier.","DOI":"10.1016\/B978-0-323-91111-5.00001-9"},{"key":"ref_3","first-page":"101209","article-title":"Pharmaceutical Applications of 3D Printing","volume":"34","author":"Chen","year":"2020","journal-title":"Addit. Manuf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1007\/s13346-020-00737-0","article-title":"3D Printing for Oral Drug Delivery: A New Tool to Customize Drug Delivery","volume":"10","author":"Pandey","year":"2020","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wang, S., Chen, X., Han, X., Hong, X., Li, X., Zhang, H., Li, M., Wang, Z., and Zheng, A. (2023). A Review of 3D Printing Technology in Pharmaceutics: Technology and Applications, Now and Future. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020416"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gueche, Y.A., Sanchez-Ballester, N.M., Cailleaux, S., Bataille, B., and Soulairol, I. (2021). Selective Laser Sintering (SLS), a New Chapter in the Production of Solid Oral Forms (SOFs) by 3D Printing. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13081212"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ijpharm.2018.11.048","article-title":"Powder Bed 3D-Printing of Highly Loaded Drug Delivery Devices with Hydroxypropyl Cellulose as Solid Binder","volume":"555","author":"Infanger","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1080\/03639045.2020.1734018","article-title":"Semi-Solid Extrusion 3D Printing ODFs: An Individual Drug Delivery System for Small Scale Pharmacy","volume":"46","author":"Yan","year":"2020","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_9","first-page":"798","article-title":"3D Printing Preview for Stereo-Lithography Based on Photopolymerization Kinetic Models","volume":"5","author":"Gao","year":"2020","journal-title":"Bioact. Mater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ijpharm.2017.06.082","article-title":"Selective Laser Sintering (SLS) 3D Printing of Medicines","volume":"529","author":"Fina","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"124161","DOI":"10.1016\/j.ijpharm.2024.124161","article-title":"Powder Bed Fusion\u2013Laser Beam (PBF-LB) Three-Dimensional (3D) Printing: Influence of Laser Hatching Distance on the Properties of Zolpidem Tartrate Tablets","volume":"657","author":"Adamov","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ijpharm.2017.05.021","article-title":"Development of Modified Release 3D Printed Tablets (Printlets) with Pharmaceutical Excipients Using Additive Manufacturing","volume":"527","author":"Goyanes","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Tabriz, A.G., Gonot-Munck, Q., Baudoux, A., Garg, V., Farnish, R., Katsamenis, O.L., Hui, H.-W., Boersen, N., Roberts, S., and Jones, J. (2023). 3D Printing of Personalised Carvedilol Tablets Using Selective Laser Sintering. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15092230"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Basit, A.W. (2018). 3D Printing of Pharmaceuticals, Springer. AAPS Advances in the Pharmaceutical Sciences Serise.","DOI":"10.1007\/978-3-319-90755-0"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s00170-005-0217-4","article-title":"Verani Building Porous Biopolymeric Microstructures for Controlled Drug Delivery Devices Using Selective Laser Sintering","volume":"31","author":"Leong","year":"2006","journal-title":"Int. J. Adv. Manuf. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.addr.2021.04.025","article-title":"Advances in Powder Bed Fusion 3D Printing in Drug Delivery and Healthcare","volume":"174","author":"Awad","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"120127","DOI":"10.1016\/j.ijpharm.2020.120127","article-title":"Oral Preparations with Tunable Dissolution Behavior Based on Selective Laser Sintering Technique","volume":"593","author":"Yang","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s11095-018-2531-1","article-title":"An Overview of 3D Printing Technologies for Soft Materials and Potential Opportunities for Lipid-Based Drug Delivery Systems","volume":"36","author":"Vithani","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijpharm.2018.02.015","article-title":"Fabricating 3D Printed Orally Disintegrating Printlets Using Selective Laser Sintering","volume":"541","author":"Fina","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1208\/s12249-020-01775-0","article-title":"Formulation Optimization of Selective Laser Sintering 3D-Printed Tablets of Clindamycin Palmitate Hydrochloride by Response Surface Methodology","volume":"21","author":"Mohamed","year":"2020","journal-title":"AAPS PharmSciTech"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Aikawa, S., Tanaka, H., Ueda, H., Maruyama, M., and Higaki, K. (2022). Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010084"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liu, J., Grohganz, H., L\u00f6bmann, K., Rades, T., and Hempel, N.-J. (2021). Co-Amorphous Drug Formulations in Numbers: Recent Advances in Co-Amorphous Drug Formulations with Focus on Co-Formability, Molar Ratio, Preparation Methods, Physical Stability, In Vitro and In Vivo Performance, and New Formulation Strategies. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13030389"},{"key":"ref_23","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":"Futur. J. Pharm. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1124\/pr.112.007252","article-title":"Pharmacogenetics and Cardiovascular Disease\u2014Implications for Personalized Medicine","volume":"65","author":"Johnson","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"ref_25","unstructured":"(2022). European Pharmacopoeia, European Directorate for the Quality of Medicines & HealthCare. [11th ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"118651","DOI":"10.1016\/j.ijpharm.2019.118651","article-title":"Understanding the Effects of Formulation and Process Variables on the Printlets Quality Manufactured by Selective Laser Sintering 3D Printing","volume":"570","author":"Mohamed","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_27","unstructured":"(2024). The United States Pharmacopeia\u2013National Formulary 2024 (USP\u2013NF 2024), The United States Pharmacopeial Convention (USP)."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Vod\u00e1\u010dkov\u00e1, P., Vran\u00edkov\u00e1, B., Sva\u010dinov\u00e1, P., Franc, A., Elbl, J., Musel\u00edk, J., Kubal\u00e1k, R., and Soln\u00fd, T. (2018). Evaluation and Comparison of Three Types of Spray Dried Coprocessed Excipient Avicel\u00ae for Direct Compression. BioMed Res. Int., 2018.","DOI":"10.1155\/2018\/2739428"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1208\/s12249-016-0616-x","article-title":"Pharmaceutical Salts of Carvedilol: Polymorphism and Physicochemical Properties","volume":"18","author":"Hiendrawan","year":"2017","journal-title":"AAPS PharmSciTech"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"856","DOI":"10.3109\/10837450.2015.1073740","article-title":"Evaluation and Correlation of the Physicochemical Properties of Carvedilol","volume":"21","author":"Alves","year":"2016","journal-title":"Pharm. Dev. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ijpharm.2018.02.011","article-title":"Optimization of Formulation and Process Parameters for the Production of Carvedilol Nanosuspension by Wet Media Milling","volume":"540","author":"Kachrimanis","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.apt.2015.05.004","article-title":"A Multivariate Approach Applied to Quality on Particle Engineering of Spray-Dried Mannitol","volume":"26","author":"Lanchote","year":"2015","journal-title":"Adv. Powder Technol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Altay Benetti, A., Bianchera, A., Buttini, F., Bertocchi, L., and Bettini, R. (2021). Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13081113"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mad\u017earevi\u0107, M., Medarevi\u0107, \u0110., Pavlovi\u0107, S., Ivkovi\u0107, B., \u0110uri\u0161, J., and Ibri\u0107, S. (2021). Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets\u2014Application of the Decision Tree Model. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111969"},{"key":"ref_35","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_36","doi-asserted-by":"crossref","unstructured":"Andrade, J., Gonz\u00e1lez-Mart\u00ednez, C., and Chiralt, A. (2020). The Incorporation of Carvacrol into Poly (Vinyl Alcohol) Films Encapsulated in Lecithin Liposomes. Polymers, 12.","DOI":"10.3390\/polym12020497"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.powtec.2012.12.038","article-title":"Soluplus\u00ae: A Novel Polymeric Solubilizer for Optimization of Carvedilol Solid Dispersions: Formulation Design and Effect of Method of Preparation","volume":"237","author":"Shamma","year":"2013","journal-title":"Powder Technol."},{"key":"ref_38","unstructured":"Kor, I., and Wizel, S. (2004). Crystalline Solids of Carvedilol and Processes for Their Preparation. (6,710,184 B2), U. S. Patent."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"121033","DOI":"10.1016\/j.ijpharm.2021.121033","article-title":"Potential Application of Low Molecular Weight Excipients for Amorphization and Dissolution Enhancement of Carvedilol","volume":"608","author":"Kachrimanis","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v21.i3.10","article-title":"Amorphous Drug Delivery Systems: Molecular Aspects, Design, and Performance","volume":"21","author":"Kaushal","year":"2004","journal-title":"Crit. Rev. Ther. Drug Carr. Syst."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Narang, A.S., and Boddu, S.H.S. (2015). Excipients That Facilitate Amorphous Drug Stabilization. Excipient Applications in Formulation Design and Drug Delivery, Springer International Publishing.","DOI":"10.1007\/978-3-319-20206-8"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.xphs.2020.11.012","article-title":"Selective Laser Sintering 3-Dimensional Printing as a Single Step Process to Prepare Amorphous Solid Dispersion Dosage Forms for Improved Solubility and Dissolution Rate","volume":"110","author":"Davis","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"ref_43","first-page":"100148","article-title":"Releasing Fast and Slow: Non-Destructive Prediction of Density and Drug Release from SLS 3D Printed Tablets Using NIR Spectroscopy","volume":"5","author":"Trenfield","year":"2023","journal-title":"Int. J. Pharm. X"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/1\/6\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:59:24Z","timestamp":1760115564000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/1\/6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,24]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["pharmaceutics17010006"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17010006","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,24]]}}}