{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:18:24Z","timestamp":1793107104411,"version":"4.5.0"},"reference-count":25,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Economy, Science and Digital Society, Free State of Thuringia","award":["2024 INP 0136"],"award-info":[{"award-number":["2024 INP 0136"]}]},{"DOI":"10.13039\/501100004403","name":"Th\u00fcringer Aufbaubank","doi-asserted-by":"crossref","award":["WE 180124"],"award-info":[{"award-number":["WE 180124"]}],"id":[{"id":"10.13039\/501100004403","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Introduction: Levodopa (LD) is the most efficacious antiparkinsonian drug. However, long-term conventional LD treatment of Parkinson\u2019s disease (PD) is frequently associated with motor complications. This can be attributed to pulsatile dopaminergic stimulation given the short LD half-life of conventional dosage forms. Tablets capable of delivering more stable and sustained dopaminergic stimulation would better mimic the brain\u2019s natural dopamine activity. Methods: In this study, 3D screen printing technology was used to manufacture oral dosage forms characterized by the sequential release of Carbidopa and Levodopa. This was achieved by separating the two compounds into different compartments within the same dosage form, which were arranged (LXM.5-1) or formulated (LXM.5-2) in a specific way. Both novel dosage forms were compared to conventional immediate release forms such as Sinemet\u00ae. The physicochemical properties of the resulting tablets, LXM.5-1 and LXM.5-2, were assessed in accordance with the USP. Their pharmacokinetic profiles were defined in pigs. Results: The physicochemical properties of LXM.5-1 and LXM.5-2 complied with regulatory requirements. Dissolution studies revealed sequential CD and LD release for both novel dosage forms. They differed regarding the interval between CD and LD release which was shorter for LXM.5-1. PK studies demonstrated that both novel dosage forms exhibited higher LD bioavailability in comparison to Sinemet\u00ae, which was 211.36% and 383.64% for LXM.5-1 and LXM.5-2, respectively. Furthermore, blood levels were more stable and sustained, particularly for LXM.5-2. Conclusions: We conclude that 3D screen-printed LXM.5-1 and LXM.5-2 and variations thereof have the potential to transform the pharmacotherapy of Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/pharmaceutics17121507","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:02:07Z","timestamp":1763974927000},"page":"1507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Three-Dimensional Screen Printing Technology Enables Sequential Release of Carbidopa and Levodopa\u2014A New Approach Improving Levodopa Delivery for Treating Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"17","author":[{"given":"Marcel","family":"Enke","sequence":"first","affiliation":[{"name":"Laxxon Medical GmbH, Otto-Schott-Str. 15, 07745 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-8850","authenticated-orcid":false,"given":"Moritz","family":"B\u00fcnger","sequence":"additional","affiliation":[{"name":"Clinical Centre for Population Medicine in Fish, Pigs and Poultry, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Aedtner","sequence":"additional","affiliation":[{"name":"Laxxon Medical GmbH, Otto-Schott-Str. 15, 07745 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kastner","sequence":"additional","affiliation":[{"name":"Laxxon Medical GmbH, Otto-Schott-Str. 15, 07745 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franka","family":"Gruschwitz","sequence":"additional","affiliation":[{"name":"Laxxon Medical GmbH, Otto-Schott-Str. 15, 07745 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"K\u00fchne","sequence":"additional","affiliation":[{"name":"Laxxon Medical GmbH, Otto-Schott-Str. 15, 07745 Jena, Germany"},{"name":"Laxxon Medical Corp, 261 Madison Ave, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Czernik-Schulz","sequence":"additional","affiliation":[{"name":"SE Tylose GmbH, Kasteler Str. 45, 65203 Wiesbaden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Greeley","sequence":"additional","affiliation":[{"name":"Northwest Neurological, PLLC, 1520 W 3rd Avenue, Spokane, WA 99201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Volc","sequence":"additional","affiliation":[{"name":"Atomos Klinik Waehring, Kreuzgasse 18\u201319, 1180 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5037-7269","authenticated-orcid":false,"given":"Andrea","family":"Buzachnich-Ladinig","sequence":"additional","affiliation":[{"name":"Clinical Centre for Population Medicine in Fish, Pigs and Poultry, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Schneeberger","sequence":"additional","affiliation":[{"name":"Laxxon Medical GmbH, Otto-Schott-Str. 15, 07745 Jena, Germany"},{"name":"Laxxon Medical Corp, 261 Madison Ave, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S1474-4422(06)70471-9","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"5","author":"Breteler","year":"2006","journal-title":"Lancet Neurol."},{"key":"ref_2","unstructured":"(2025, March 10). WHO Fact Sheet Parkinson. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/parkinson-disease."},{"key":"ref_3","first-page":"S3","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. Park. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/mds.20213","article-title":"Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: Status and recommendations The Movement Disorder Society Task Force on rating scales for Parkinson\u2019s disease","volume":"19","author":"Goetz","year":"2004","journal-title":"Mov. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1136\/jnnp.2007.131045","article-title":"Parkinson\u2019s disease: Clinical features and diagnosis","volume":"79","author":"Jankovic","year":"2008","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1503\/cmaj.151179","article-title":"An update on the diagnosis and treatment of Parkinson disease","volume":"188","author":"Rizek","year":"2016","journal-title":"Can. Med Assoc. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and Treatment of Parkinson Disease","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jns.2012.05.029","article-title":"Treatment patterns and associated costs with Parkinson\u2019s disease levodopa induced dyskinesia","volume":"319","author":"Suh","year":"2012","journal-title":"J. Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/ncpneuro0222","article-title":"Drug Insight: Continuous dopaminergic stimulation in the treatment of Parkinson\u2019s disease","volume":"2","author":"Olanow","year":"2006","journal-title":"Nat. Clin. Pract. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1365-2125.1986.tb02913.x","article-title":"The pharmacokinetics of intravenous and oral levodopa in patients with Parkinson\u2019s disease who exhibit on-off fluctuations","volume":"22","author":"Hardie","year":"1986","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"123101","DOI":"10.1016\/j.ijpharm.2023.123101","article-title":"3D screen printing technology enables fabrication of oral drug dosage forms with freely tailorable release profiles","volume":"642","author":"Enke","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"120096","DOI":"10.1016\/j.ijpharm.2020.120096","article-title":"3D screen printing\u2014An innovative technology for large-scale manufacturing of pharmaceutical dosage forms","volume":"592","author":"Moldenhauer","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"251","DOI":"10.56808\/3027-7922.2461","article-title":"Increasing the solubility of levodopa and carbidopa using ionization approach","volume":"44","author":"Krisai","year":"2020","journal-title":"Thai J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E118","DOI":"10.1208\/pt070117","article-title":"Intragastric floating drug delivery system of cefuroxime axetil: In vitro evaluation","volume":"7","author":"Patel","year":"2006","journal-title":"AAPS PharmSciTech"},{"key":"ref_15","unstructured":"United States Pharmacopeial Convention (2018). Chemical Medicines Monographs 4. Carbidopa and Levodopa Extended-Release Tablets. United States Pharmacopeia, United States Pharmacopeial Convention."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/jms.1973","article-title":"Development and validation of a high-performance liquid chromatography\u2013electrospray ionization\u2013MS\/MS method for the simultaneous quantitation of levodopa and carbidopa in human plasma","volume":"46","author":"Byrro","year":"2011","journal-title":"J. Mass Spectrom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.2174\/157488407781668802","article-title":"The Pharmacokinetics and Pharmacodynamics of Levodopa in the Treatment of Parkinsons Disease","volume":"2","author":"Khor","year":"2007","journal-title":"Curr. Clin. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/ana.410180505","article-title":"The effect of carbidopa on the pharmacokinetics of intravenously administered levodopa: The mechanism of action in the treatment of parkinsonism","volume":"18","author":"Nutt","year":"1985","journal-title":"Ann. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1111\/ene.15734","article-title":"Gastrointestinal barriers to levodopa transport and absorption in Parkinson\u2019s disease","volume":"30","author":"Leta","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1177\/00912700022009585","article-title":"Variable Absorption of Carbidopa Affects Both Peripheral and Central Levodopa Metabolism","volume":"40","author":"Durso","year":"2000","journal-title":"J. Clin. Pharmacol."},{"key":"ref_21","first-page":"763","article-title":"A critical review on tablet disintegration","volume":"21","author":"Quodbach","year":"2015","journal-title":"Pharm. Dev. Technol."},{"key":"ref_22","unstructured":"(2025, November 07). SINEMET\u00ae. Available online: https:\/\/www.organon.com\/product\/usa\/pi_circulars\/s\/sinemet\/sinemet_pi.pdf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1124\/jpet.114.216317","article-title":"The Molecular Mechanism of Intestinal Levodopa Absorption and Its Possible Implications for the Treatment of Parkinson\u2019s Disease","volume":"351","author":"Camargo","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_24","first-page":"25","article-title":"Pharmacokinetics and bioavailability of Sinemet CR: A summary of human studies","volume":"39","author":"Yeh","year":"1989","journal-title":"Neurology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.parkreldis.2022.08.002","article-title":"Motor and nonmotor symptoms in patients treated with 24-h daily levodopa-carbidopa intestinal gel infusion: Analysis of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS)","volume":"105","author":"Svenningsson","year":"2022","journal-title":"Park. Relat. Disord."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/12\/1507\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T05:17:30Z","timestamp":1764047850000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/12\/1507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,22]]},"references-count":25,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["pharmaceutics17121507"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17121507","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,22]]}}}