{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:02:15Z","timestamp":1787029335865,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"crossref","award":["RS-2023-00230559"],"award-info":[{"award-number":["RS-2023-00230559"]}],"id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"crossref","award":["RS-2023-00230655"],"award-info":[{"award-number":["RS-2023-00230655"]}],"id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RS-2023-00230559"],"award-info":[{"award-number":["RS-2023-00230559"]}],"id":[{"id":"https:\/\/ror.org\/008nkqk13","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2023-00230655"],"award-info":[{"award-number":["RS-2023-00230655"]}],"id":[{"id":"https:\/\/ror.org\/008nkqk13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: This study aimed to investigate, from a scientific and formulation perspective, an oral semaglutide tablet incorporating sodium caprate (C10) as an intestinal absorption enhancer and to optimize its formulation performance using a Quality by Design (QbD)-based approach. Semaglutide\u2014a peptide-based therapeutic\u2014provides effective glycemic control and weight reduction; however, its extremely low oral bioavailability has limited administration to subcutaneous injection. Although various attempts have been made to improve peptide absorption, achieving consistent delivery through oral routes remains a significant challenge due to enzymatic degradation and poor membrane permeability. Methods: To overcome these limitations, an absorption enhancer (sodium caprate) was incorporated to enhance oral absorption, and a Quality by Design (QbD)-based approach was applied to systematically guide formulation development. Following the definition of the Quality Target Product Profile and critical quality attributes, risk assessments (Preliminary Hazard Analysis and Failure Mode and Effects Analysis) were conducted to identify key formulation factors. A design of experiments approach was then employed to determine the optimal tablet composition. Results: Consequently, the resulting formulation met all predefined quality criteria, including hardness, disintegration, friability, and content uniformity. In addition, the in vitro dissolution profile demonstrated a release pattern comparable to that of the reference product, with similarity factor values of 74.4, 74.7, and 71.3 at pH 1.2, 4.0, and 6.8, respectively. Conclusions: These findings indicate that the formulation can achieve consistent and reproducible quality performance as an oral semaglutide dosage form. The QbD-based formulation design strategy presented in this study provides a robust and broadly applicable approach for developing oral delivery systems for peptide drugs, including semaglutide, and ultimately provides useful formulation insight for future peptide-based oral delivery research.<\/jats:p>","DOI":"10.3390\/pharmaceutics18040440","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T07:57:55Z","timestamp":1775116675000},"page":"440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Quality by Design-Based Formulation Development of an Oral Semaglutide Tablet"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1955-153X","authenticated-orcid":false,"given":"Ji-Hyeon","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Biopharmaceutical Chemistry, Kookmin University, Seoul 02707, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do-Hyub","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutical Chemistry, Kookmin University, Seoul 02707, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7744-8573","authenticated-orcid":false,"given":"Joo-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutical Chemistry, Kookmin University, Seoul 02707, Republic of Korea"},{"name":"Department of Biopharmaceutical Chemistry, School of Applied Chemistry, Kookmin University, Seoul 02707, Republic of Korea"},{"name":"Department of Pharmaceutical Engineering, Kookmin University, Seoul 02707, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1021\/jacs.5b09974","article-title":"Emerging Frontiers in Drug Delivery","volume":"138","author":"Tibbitt","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.drudis.2021.01.020","article-title":"New perspectives in oral peptide delivery","volume":"26","author":"Zizzari","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.2147\/PPA.S277676","article-title":"Real-world adherence and discontinuation of glucagon-like peptide-1 receptor agonists therapy in type 2 diabetes mellitus patients in the United States","volume":"14","author":"Weiss","year":"2020","journal-title":"Patient Prefer. Adherence"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.addr.2020.05.007","article-title":"Systemic delivery of peptides by the oral route: Formulation and medicinal chemistry approaches","volume":"157","author":"Brayden","year":"2020","journal-title":"Adv. Drug Deliv. 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Biophys Acta"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/4\/440\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:11:28Z","timestamp":1775448688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/4\/440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["pharmaceutics18040440"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18040440","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]}}}