{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:26:43Z","timestamp":1788953203853,"version":"build-2803163510"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Buccal films have attracted continued interest due to their several advantages. However, developing effective buccal films for hydrophilic drugs remains challenging due to limited buccal permeability. Captopril, a water-soluble ACEI, represents a suitable model for evaluating buccal films. Chitosan\u2013ascorbate has previously been studied in solution for its cytotoxicity and permeation-enhancing properties. However, its performance as a buccal-film dosage form requires further investigation. The present study extends earlier formulation work by evaluating the in vitro cytotoxicity, permeability, and stability of captopril-loaded chitosan\u2013ascorbate buccal films. Methods: Blank and captopril-loaded films were assessed. Cytotoxicity and permeability were evaluated using TR146 cells and compared with chitosan\u2013acetate films as a reference. Accelerated stability test (40 \u00b0C\/75% RH, three months) was performed to monitor moisture content, mechanical properties, and drug content. FT-IR spectroscopy was used to investigate potential chemical interactions. Results: All films maintained cell viability above 80%. Chitosan\u2013ascorbate films significantly increased captopril permeation compared with chitosan\u2013acetate films, achieving up to a 12\u201316-fold increase in cumulative drug permeation. The stability test did not reveal any new chemical reactions or interactions based on FT-IR analysis, indicating that the polymer system remained structurally stable; however, it showed continuous moisture uptake, slight deterioration of mechanical properties and a decrease in drug content. Conclusions: This study provides an in vitro, dosage-form\u2013level evaluation of captopril-loaded chitosan\u2013ascorbate buccal films, demonstrating acceptable cytocompatibility and moderate enhancement of permeability. However, significant moisture sensitivity under accelerated conditions can represent limitations, highlighting the importance of protective packaging or further formulation optimization to overcome this.<\/jats:p>","DOI":"10.3390\/ph19071058","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:40:09Z","timestamp":1783525209000},"page":"1058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigation of Cytotoxicity, Permeability, and Stability of Captopril-Loaded Chitosan-Ascorbate Buccal Films"],"prefix":"10.3390","volume":"19","author":[{"given":"Hala","family":"Rayya","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, E\u00f6tv\u00f6s u. 6., H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8446-3739","authenticated-orcid":false,"given":"Raghad","family":"Alsheikh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, H-4002 Debrecen, Hungary"},{"name":"Doctorate School of Pharmaceutical Sciences, University of Debrecen, H-4002 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5477-0540","authenticated-orcid":false,"given":"D\u00e1niel","family":"Nemes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, H-4002 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lajos","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Institute of Chemistry, Faculty of Science and Technology, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"G\u00e9za","family":"Regdon","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, E\u00f6tv\u00f6s u. 6., H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8663-2890","authenticated-orcid":false,"given":"Ildik\u00f3","family":"B\u00e1cskay","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, H-4002 Debrecen, Hungary"},{"name":"Doctorate School of Pharmaceutical Sciences, University of Debrecen, H-4002 Debrecen, Hungary"},{"name":"Institute of Healthcare Industry, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-6831","authenticated-orcid":false,"given":"Katalin","family":"Krist\u00f3","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, E\u00f6tv\u00f6s u. 6., H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriszti\u00e1n","family":"Paml\u00e9nyi","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, E\u00f6tv\u00f6s u. 6., H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1055\/a-2560-9884","article-title":"Drug Delivery Approaches for Buccal and Sublingual Administration","volume":"75","author":"Ahmad","year":"2025","journal-title":"Drug Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.47583\/ijpsrr.2022.v74i01.027","article-title":"Recent Trends and Advances in Buccal Film Drug Delivery System: An Innovative Pharmaceutical Dosage Form Technology","volume":"27","author":"Rajeshkumar","year":"2022","journal-title":"Int. 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