{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:15:55Z","timestamp":1790266555186,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T00:00:00Z","timestamp":1743811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u2018Grigore T. Popa\u2019 University of Medicine and Pharmacy, Iasi, Romania","award":["1468\/20.11.2024"],"award-info":[{"award-number":["1468\/20.11.2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Rheumatoid arthritis is a chronic autoimmune disease that leads to severe disability and requires improved therapeutic strategies to optimize anti-inflammatory treatment. This study aimed to address this challenge by developing and characterizing an extended-release polymer matrix tablet containing ketoprofen and a ketoprofen\u2013\u03b2-cyclodextrin complex with enhanced therapeutic properties. The objective was to improve inflammation management and therapeutic outcomes using a novel delivery system based on the inclusion of the active substance in cyclodextrin complexes. Methods: Tablets were formulated using ketoprofen and ketoprofen\u2013\u03b2-cyclodextrin complexes combined with hydrophilic polymers such as Carbopol\u00ae 971P NF, Kollidon\u00ae VA 64, and MethocelTM K4M. The complexes were obtained via the coprecipitation method to improve bioavailability. The kinetics of the release of ketoprofen, ketoprofen\u2013\u03b2-cyclodextrin complex (2:1), and ketoprofen\u2013\u03b2-cyclodextrin complex (1:1) from the tablets were investigated in vitro in artificial gastric and intestinal fluids, and drug release profiles were established. Advanced mathematical models were used to describe the nonlinear behavior of the drug\u2013polymer systems. Results: The inclusion of ketoprofen in the \u03b2-cyclodextrin complexes was confirmed, revealing distinct release profiles. Tablets (K-3 F-3) containing the 1:1 complex showed rapid release (96.2% in 4\u20137 h), while tablets (K-1 F-4) containing free ketoprofen released 76% over 9\u201311 h. Higher polymer concentrations slowed the release due to gel barrier formation. Pharmacotechnical and stability tests supported their suitability as extended-release forms. A multifractal modeling approach described the release dynamics, treating the polymer\u2013drug matrix as a complex system, with release curves characterized by variations in the fractal dimension and resolution. Conclusions: Specific hydrophilic polymer combinations effectively prolonged ketoprofen release. The developed matrix tablets, which were evaluated via in vitro studies and mathematical modeling, show promise for improving therapeutic outcomes and patient compliance during rheumatoid arthritis treatment.<\/jats:p>","DOI":"10.3390\/pharmaceutics17040474","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T05:59:00Z","timestamp":1744091940000},"page":"474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Formulation and In Vitro Evaluation of Matrix Tablets Containing Ketoprofen\u2013Beta Cyclodextrin Complex for Enhanced Rheumatoid Arthritis Therapy: Experimental and Computational Insights"],"prefix":"10.3390","volume":"17","author":[{"given":"Monica","family":"Stamate Cretan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6447-0958","authenticated-orcid":false,"given":"Lacramioara","family":"Ochiuz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8233-8862","authenticated-orcid":false,"given":"Vlad","family":"Ghizdovat","sequence":"additional","affiliation":[{"name":"Biophysics and Medical Physics Department, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Molcalut","sequence":"additional","affiliation":[{"name":"Faculty of Physics, \u201cAlexandru Ioan Cuza\u201d University, Blvd. Carol I, No. 11, Iasi 700506, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maricel","family":"Agop","sequence":"additional","affiliation":[{"name":"Department of Physics, \u201cGheorghe Asachi\u201d Technical University of Iasi, Prof. Dr. Docent Dimitrie Mangeron Rd., No. 59A, 700050 Iasi, Romania"},{"name":"Romanian Scientists Academy, 54 Splaiul Independentei, 050094 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Anatolia","family":"Gafi\u021banu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3864-0551","authenticated-orcid":false,"given":"Alexandra","family":"Barsan (Bujor)","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5250-0109","authenticated-orcid":false,"given":"Mousa","family":"Sha\u2019at","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1734-9060","authenticated-orcid":false,"given":"Ciprian","family":"Stamate","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Mechatronics and Robotics, \u201cGheorghe Asachi\u201d Technical University of Iasi, Prof. Dr. Docent Dimitrie Mangeron Rd., No. 43, 700050 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e509","DOI":"10.1002\/mco2.509","article-title":"Rheumatoid arthritis: Pathogenesis and therapeutic advances","volume":"5","author":"Gao","year":"2024","journal-title":"MedComm"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3899\/jrheum.2023-0334","article-title":"Rheumatoid Arthritis: The Continuum of Disease and Strategies for Prediction, Early Intervention, and Prevention","volume":"51","author":"Deane","year":"2024","journal-title":"J. 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