{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:04:18Z","timestamp":1785416658956,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"West University of Timi\u0219oara","award":["CNFIS-FDI-2026-F-0369"],"award-info":[{"award-number":["CNFIS-FDI-2026-F-0369"]}]},{"award":["CNFIS-FDI-2026-F-0369"],"award-info":[{"award-number":["CNFIS-FDI-2026-F-0369"]}],"id":[{"id":"https:\/\/ror.org\/0583a0t97","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Oral administration of narrow therapeutic index anticoagulants like phenprocoumon (PHP) necessitates careful control of the kinetic release of the drug to avoid dose dumping and severe haemorrhagic effects. This study was carried out to prepare and characterize novel PHP delivery systems based on \u03ba-carrageenan hydrogels, exploring the importance of potassium ion (K+) stabilization in controlling the release process. FT-IR, TG\/DTG, and in vitro release studies were employed in combination with a new validated RP-HPLC assay. FT-IR and thermal analysis results showed that PHP is physically encapsulated into the polysaccharide matrix, where there are no chemical incompatibilities between them. Furthermore, potassium ions increase the stability and heat resistance of the polymer network. However, when K+ was considered for modelling the kinetic release using the Korsmeyer\u2013Peppas equation, it was observed that PHP is released from the K+ stabilized matrix in a relaxation dominated diffusion-controlled transport. Ionic cross-linking effectively reduces the initial burst effect, demonstrating that these matrices are promising vehicles for the sustained delivery of phenprocoumon.<\/jats:p>","DOI":"10.3390\/molecules31142540","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T09:20:39Z","timestamp":1784712039000},"page":"2540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Formulation and Analytical Characterization of Phenprocoumon-Loaded \u03ba-Carrageenan Hydrogels for Controlled-Release Applications"],"prefix":"10.3390","volume":"31","author":[{"given":"Iulia","family":"Gallo","sequence":"first","affiliation":[{"name":"Research Centre for Thermal Analysis in Environmental Problems\/ICAM-Advanced Environmental Research Institute, West University of Timisoara, Oituz Street 4, 300233 Timisoara, Romania"},{"name":"Doctoral School of Exact Sciences and Natural Sciences, West University of Timi\u0219oara, Pestalozzi Street 16, 300115 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camelia","family":"Epuran","sequence":"additional","affiliation":[{"name":"Research Centre for Thermal Analysis in Environmental Problems\/ICAM-Advanced Environmental Research Institute, West University of Timisoara, Oituz Street 4, 300233 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3556-3957","authenticated-orcid":false,"given":"Ion","family":"Fratilescu","sequence":"additional","affiliation":[{"name":"Research Centre for Thermal Analysis in Environmental Problems\/ICAM-Advanced Environmental Research Institute, West University of Timisoara, Oituz Street 4, 300233 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"\u0218tefan-Panti\u0219","sequence":"additional","affiliation":[{"name":"Research Centre for Thermal Analysis in Environmental Problems\/ICAM-Advanced Environmental Research Institute, West University of Timisoara, Oituz Street 4, 300233 Timisoara, Romania"},{"name":"Doctoral School of Exact Sciences and Natural Sciences, West University of Timi\u0219oara, Pestalozzi Street 16, 300115 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0324-1163","authenticated-orcid":false,"given":"Alexandru","family":"Pahomi","sequence":"additional","affiliation":[{"name":"Research Centre for Thermal Analysis in Environmental Problems\/ICAM-Advanced Environmental Research Institute, West University of Timisoara, Oituz Street 4, 300233 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0958-4992","authenticated-orcid":false,"given":"Mihaela Maria","family":"Budiul","sequence":"additional","affiliation":[{"name":"Research Centre for Thermal Analysis in Environmental Problems\/ICAM-Advanced Environmental Research Institute, West University of Timisoara, Oituz Street 4, 300233 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7480-7486","authenticated-orcid":false,"given":"Titus","family":"Vlase","sequence":"additional","affiliation":[{"name":"Research Centre for Thermal Analysis in Environmental Problems\/ICAM-Advanced Environmental Research Institute, West University of Timisoara, Oituz Street 4, 300233 Timisoara, Romania"},{"name":"Doctoral School of Exact Sciences and Natural Sciences, West University of Timi\u0219oara, Pestalozzi Street 16, 300115 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1307-7010","authenticated-orcid":false,"given":"Gabriela","family":"Vlase","sequence":"additional","affiliation":[{"name":"Research Centre for Thermal Analysis in Environmental Problems\/ICAM-Advanced Environmental Research Institute, West University of Timisoara, Oituz Street 4, 300233 Timisoara, Romania"},{"name":"Doctoral School of Exact Sciences and Natural Sciences, West University of Timi\u0219oara, Pestalozzi Street 16, 300115 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Berradi, A., Aziz, F., Achaby, M.E., Ouazzani, N., and Mandi, L. (2023). A Comprehensive Review of Polysaccharide-Based Hydrogels as Promising Biomaterials. Polymers, 15.","DOI":"10.3390\/polym15132908"},{"key":"ref_2","first-page":"170","article-title":"Nanotechnology at Work: Hydrogel Drug Delivery Architectures","volume":"14","author":"Aher","year":"2024","journal-title":"Drug Deliv. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141295","DOI":"10.1016\/j.ijbiomac.2025.141295","article-title":"Enhanced dual-drug loaded \u03ba-carrageenan\/agar hydrogel films for wound dressing: Optimizing swelling and drug release","volume":"306","author":"Arayesh","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103528","DOI":"10.1016\/j.mtcomm.2022.103528","article-title":"Optimization, characterization, and evaluation of carrageenan\/alginate\/poloxamer\/curcumin hydrogel film as a functional wound dressing material","volume":"31","year":"2022","journal-title":"Mater. Today Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123283","DOI":"10.1016\/j.ijbiomac.2023.123283","article-title":"Curcumin-loaded alginate hydrogels for cancer therapy and wound healing applications: A review","volume":"232","author":"Sood","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"124987","DOI":"10.1016\/j.colsurfa.2020.124987","article-title":"Preparation and characterization of environmentally friendly agar\/\u03ba-carrageenan\/montmorillonite nanocomposite hydrogels","volume":"602","author":"Polat","year":"2020","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"231952","DOI":"10.1098\/rsos.231952","article-title":"Kappa-carrageenan and sodium alginate-based pH-responsive hydrogels for controlled release of methotrexate","volume":"11","author":"Qureshi","year":"2024","journal-title":"R. Soc. Open Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sepe, F., Valentino, A., Marcolongo, L., Petillo, O., Conte, R., Margarucci, S., Peluso, G., and Calarco, A. (2025). Marine-Derived Polysaccharide Hydrogels as Delivery Platforms for Natural Bioactive Compounds. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020764"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.carbpol.2013.12.008","article-title":"Carrageenan and its applications in drug delivery","volume":"103","author":"Li","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Russo Spena, S., and Grizzuti, N. (2025). \u03ba-Carrageenan and Its Synergistic Blends: Next-Generation Food Gels. Gels, 11.","DOI":"10.3390\/gels11120976"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1080\/10408398.2018.1481822","article-title":"Clarifying the confusion between poligeenan, degraded carrageenan, and carrageenan: A review of the chemistry, nomenclature, and in vivo toxicology by the oral route","volume":"59","author":"McKim","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Faria, M., Bhanumathyamma, D., Reji, G.M., Kuttiyatt, A.S.B., Sivaprasad, G., Viswanathan, S.P., Ferreira, A., Jose, J., Sadasivan, S.M., and Pothan, L.A. (2025). Diffusion-Controlled Release of Bromelain from k-Carrageenan Nanocomposite Hydrogels Reinforced with Bio-Derived Nanofillers. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262311438"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Postolovi\u0107, K.S., Antonijevi\u0107, M.D., Ljuji\u0107, B., Mileti\u0107 Kova\u010devi\u0107, M., Gazdi\u0107 Jankovi\u0107, M., and Stani\u0107, Z.D. (2022). pH-Responsive Hydrogel Beads Based on Alginate, \u03ba-Carrageenan and Poloxamer for Enhanced Curcumin, Natural Bioactive Compound, Encapsulation and Controlled Release Efficiency. Molecules, 27.","DOI":"10.3390\/molecules27134045"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sabbagh, F., Khatir, N.M., and Kiarostami, K. (2023). Synthesis and Characterization of \u03ba-Carrageenan\/PVA Nanocomposite Hydrogels in Combination with MgZnO Nanoparticles to Evaluate the Catechin Release. Polymers, 15.","DOI":"10.3390\/polym15020272"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kumar, S., Purohit, P., Panwar, S., Kharatmal, S.B., Munjal, S., Abdellattif, M.H., and Sambhaji mane, R. (2025). Ammonia-triggered disintegration of kappa-carrageenan hydrogel carrier for site-specific anti-inflammatory drug delivery. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1676330"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"138797","DOI":"10.1016\/j.ijbiomac.2024.138797","article-title":"Synthesis of photo-responsive \u03ba-carrageenan-based hydrogels for drug delivery application","volume":"289","author":"Alshammari","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Najahi-Missaoui, W., Arnold, R.D., and Cummings, B.S. (2021). Safe Nanoparticles: Are We There Yet?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010385"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.carbpol.2018.06.086","article-title":"Carrageenan based hydrogels for drug delivery, tissue engineering and wound healing","volume":"198","author":"Yegappan","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_19","first-page":"oead065","article-title":"Comparison of phenprocoumon with direct oral anticoagulants in catheter ablation of atrial fibrillation","volume":"3","author":"Gjermeni","year":"2023","journal-title":"EHJ Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e063490","DOI":"10.1136\/bmjopen-2022-063490","article-title":"Vitamin-K-antagonist phenprocoumon versus direct oral anticoagulants in patients with atrial fibrillation: A real-world analysis of German claims data","volume":"13","author":"Warkentin","year":"2023","journal-title":"BMJ Open"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lindhoff-Last, E., Birschmann, I., Bidenharn, A.J., Kuhn, J., Lindau, S., Konstantinides, S., Grottke, O., Nowak-G\u00f6ttl, U., Lucks, J., and Zydek, B. (2022). Pharmacokinetics of Phenprocoumon in Emergency Situations\u2013Results of the Prospective Observational RADOA-Registry (Reversal Agent Use in Patients Treated with Direct Oral Anticoagulants or Vitamin K Antagonists Registry). Pharmaceuticals, 15.","DOI":"10.3390\/ph15111437"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8072","DOI":"10.1039\/C3RA42347F","article-title":"A comparative study of the molecular structure, lipophilicity, solubility, acidity, absorption and polar surface area of coumarinic anticoagulants and direct thrombin inhibitors","volume":"4","author":"Remko","year":"2014","journal-title":"RSC Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1160\/TH13-06-0443","article-title":"Vitamin K antagonists in heart disease: Current status and perspectives (Section III)","volume":"110","author":"Husted","year":"2013","journal-title":"Thromb. Haemost."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100439","DOI":"10.1016\/j.bcdf.2024.100439","article-title":"Designing carrageenan-based hydrogels for drug delivery applications: Evaluation of physiochemical and biomedical properties","volume":"32","author":"Thakur","year":"2024","journal-title":"Bioact. Carbohydr. Diet. Fibre"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"117794","DOI":"10.1016\/j.carbpol.2021.117794","article-title":"Preparation, physicochemical characterization and in vitro release behavior of resveratrol-loaded oxidized gellan gum\/resistant starch hydrogel beads","volume":"260","author":"Wang","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gallo, I., Fratilescu, I., Epuran, C., Pahomi, A., Dumitrescu, M., Budiul, M.M., Gr\u0103dinaru, M., Vlase, T., and Vlase, G. (2026). Assessment of phenprocoumon stability and excipient compatibility using thermoanalytical techniques and FT-IR spectroscopy. J. Therm. Anal. Calorim.","DOI":"10.1007\/s10973-026-15762-3"},{"key":"ref_27","first-page":"459","article-title":"RP-HPLC method with uv detection for the evaluation of chitosan-graft-\u03b2-cyclodextrin\/pva hydrogels as carriers for the controlled release of vemurafenib","volume":"129","author":"Yilmaz","year":"2025","journal-title":"Rev. Med. Chir. Soc. Med. Nat. Iasi"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.foodhyd.2011.02.009","article-title":"FTIR-ATR spectroscopy as a tool for polysaccharide identification in edible brown and red seaweeds","volume":"25","year":"2011","journal-title":"Food Hydrocoll."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.ijbiomac.2020.03.087","article-title":"Studies on the physicochemical properties, gelling behavior and drug release performance of agar\/\u03ba-carrageenan mixed hydrogels","volume":"154","author":"Zhao","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"124417","DOI":"10.1016\/j.chemosphere.2019.124417","article-title":"\u03ba-Carrageenan\/Sodium alginate double-network hydrogel with enhanced mechanical properties, anti-swelling, and adsorption capacity","volume":"237","author":"Yu","year":"2019","journal-title":"Chemosphere"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"313","DOI":"10.48130\/FIA-2023-0031","article-title":"Development of \u03ba-carrageenan hydrogels with mechanically stronger structures via a solvent-replacement method","volume":"2","author":"Wang","year":"2023","journal-title":"Food Innov. Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.carbpol.2009.01.020","article-title":"Carrageenans: Biological properties, chemical modifications and structural analysis\u2014A review","volume":"77","author":"Campo","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jare.2013.07.006","article-title":"Hydrogel: Preparation, characterization, and applications: A review","volume":"6","author":"Ahmed","year":"2015","journal-title":"J. Adv. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0378-4347(00)80511-3","article-title":"Determination of the anticoagulant phenprocoumon in human plasma and urine by high-performance liquid chromatography","volume":"231","author":"Harenberg","year":"1982","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0378-4347(00)00143-2","article-title":"Sensitive stereospecific determination of acenocoumarol and phenprocoumon in plasma by high-performance liquid chromatography","volume":"742","author":"Rentsch","year":"2000","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_36","first-page":"110","article-title":"Analysis of Fickian and non-Fickian drug release from polymers","volume":"60","author":"Peppas","year":"1985","journal-title":"Pharm. Acta Helv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0928-0987(01)00095-1","article-title":"Modeling and comparison of dissolution profiles","volume":"13","author":"Costa","year":"2001","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"114260","DOI":"10.1016\/j.jconrel.2025.114260","article-title":"Highly Adhesive Asynchronous Drug-Releasing Membrane for Facial Care: Combined Anti-Acne and Anti-Inflammatory Properties","volume":"388","author":"Kang","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kim, D., Kim, D.H., Cha, J.E., Park, S., and Lee, S.H. (2025). Metal-Ion-Free Preparation of \u03ba-Carrageenan\/Cellulose Hydrogel Beads Using an Ionic Liquid Mixture for Effective Cationic Dye Removal. Gels, 11.","DOI":"10.3390\/gels11080596"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0022-2836(80)90291-0","article-title":"Cation-specific aggregation of carrageenan helices: Domain model of polymer gel structure","volume":"138","author":"Morris","year":"1980","journal-title":"J. Mol. Biol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/14\/2540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T09:21:04Z","timestamp":1784712064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/14\/2540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":40,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["molecules31142540"],"URL":"https:\/\/doi.org\/10.3390\/molecules31142540","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}