{
  "abstract": "Purpose: Gastric mucosal injury caused by long-term nonsteroidal anti-inflammatory drug therapy remains a significant clinical concern, particularly in patients with rheumatoid arthritis. In this study, we developed a three-dimensional (3D)-printed oral thin film (OTF) formulation incorporating rebamipide (REB) nanocrystals (REB-NP@OTF) with enhanced gastroprotective potential.\n\nMethods: REB nanocrystals were prepared by wet bead milling using methylcellulose and hydroxypropyl-β-cyclodextrin as stabilizers. The nanocrystals were incorporated into a polymeric OTF matrix using semi-solid extrusion-based 3D printing. Particle size was measured by nanoparticle tracking analysis using a NanoSight LM10 system, and in vitro drug release was compared with that from OTF containing micro-sized REB (REB@OTF). Gastric mucosal drug retention was evaluated using rats, and therapeutic efficacy was assessed in an indomethacin (IND)-induced gastric injury model using adjuvant-induced arthritis (AA) rats.\n\nResults: REB nanocrystals had a mean particle size of approximately 114 nm. Compared with REB@OTF, REB-NP@OTF exhibited a smoother and more uniform internal structure with densely packed particles. Both formulations satisfied the pharmacopeial criteria for weight and content uniformity; however, nanocrystal incorporation significantly altered the pharmaceutical properties. Compared to REB@OTF, REB-NP@OTF showed a 4.2-fold increase in solubility, enhanced hydration behavior, and faster drug release under simulated intestinal conditions. Importantly, particle size analysis confirmed that REB was released from REB-NP@OTF while maintaining its nanoparticulate state. In vivo studies revealed prolonged gastric mucosal retention following oral administration of REB-NP@OTF. In an IND-induced gastric acute injury model using AA rats, REB-NP@OTF markedly reduced the gastric lesion area relative to the REB@OTF containing conventional REB powder.\n\nConclusion: These findings indicate that 3D-printed REB nanocrystal OTFs represent a promising and versatile strategy for improving gastroprotective therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, Japan",
    "Faculty of Pharmaceutical Sciences, Doshisha Woman’s College of Liberal Arts, Kyotanabe, Kyoto, Japan",
    "University Startup Promotion Center, Research Promotion Headquarters, Fujita Health University, Toyoake, Aichi, Japan",
    "Faculty of Engineering, Sanyo-Onoda City University, Sanyo-Onoda, Yamaguchi, Japan",
    "Department of Pharmaceutics and PhaM. Technology, L. M. College of Pharmacy, Ahmedabad, GJ, India",
    "Laboratory of Pharmacotherapy, Tokushima Bunri University, Sanuki, Kagawa, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hiroko Otake"
    },
    {
      "affs": [
        0
      ],
      "name": "Riku Azuma"
    },
    {
      "affs": [
        0
      ],
      "name": "Fumihiko Ogata"
    },
    {
      "affs": [
        1
      ],
      "name": "Yosuke Nakazawa"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Naoki Yamamoto",
      "orcid": "0000-0002-9659-3204"
    },
    {
      "affs": [
        4
      ],
      "name": "Manju Misra"
    },
    {
      "affs": [
        5
      ],
      "name": "Masanobu Tsubaki"
    },
    {
      "affs": [
        0
      ],
      "name": "Naohito Kawasaki",
      "orcid": "0000-0002-9412-0868"
    },
    {
      "affs": [
        0
      ],
      "name": "Noriaki Nagai",
      "orcid": "0009-0007-1266-038X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5wcmp7n9076ha.bib",
  "cited_by": 0,
  "doi": "10.2147/ijn.s654551",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13730070/",
  "id": "5wcmp7n9076ha",
  "issns": [
    "1176-9114",
    "1178-2013"
  ],
  "landing_url": "https://doi.org/10.2147/ijn.s654551",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "3003|Advanced Drug Delivery Systems"
    ]
  ],
  "openalex": "W7224277990",
  "pdf_url": "https://www.mhlw.go.jp/content/11120000/000945683.pdf",
  "pmcid": "PMC13730070",
  "pmid": "42979241",
  "published": "2026-10-30",
  "publisher": "Dove Press",
  "ris": "https://research.draconitic.com/paper/5wcmp7n9076ha.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:22:43Z",
      "native_id": "PMC13730070",
      "source": "pmc",
      "url": "https://doi.org/10.2147/ijn.s654551"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3003|Advanced Drug Delivery Systems",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "3D-Printed Rebamipide Nanocrystal Oral Thin Films for Gastroprotection Against Indomethacin-Induced Gastric Lesions in Arthritic Rats",
  "title_text": "3D-Printed Rebamipide Nanocrystal Oral Thin Films for Gastroprotection Against Indomethacin-Induced Gastric Lesions in Arthritic Rats",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:22:43Z",
  "url": "https://research.draconitic.com/paper/5wcmp7n9076ha",
  "venue": "International Journal of Nanomedicine",
  "versions": []
}