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This study aimed to develop and optimize a cubosome-based nanocarrier system to enhance the oral bioavailability and sustain the release of DEM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      DEM-loaded cubosomes were prepared using glycerol monooleate (GMO) and Poloxamer 407 by melt dispersion\u2013emulsification. A Central Composite Design (CCD) was employed to optimize formulation variables based on particle size, entrapment efficiency, and drug release responses. Optimized formulations were characterized by dynamic light scattering, TEM, FT-IR, DSC, and XRD analyses.\n                      <jats:italic>In vitro<\/jats:italic>\n                      drug release and\n                      <jats:italic>in vivo<\/jats:italic>\n                      pharmacokinetic studies in Wistar rats were performed to evaluate sustained release behavior and relative oral bioavailability enhancement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The optimized cubosomes exhibited nanoscale particle size (~\u200919\u201330\u00a0nm), narrow size distribution, high entrapment efficiency (~\u200987%), and sustained biphasic drug release up to 24\u00a0h. Structural characterization supported incorporation of DEM within the lipid matrix and reduced drug crystallinity.\n                      <jats:italic>In vivo<\/jats:italic>\n                      pharmacokinetic evaluation demonstrated prolonged plasma exposure and enhanced relative bioavailability compared with the marketed formulation, with approximately 2.28-fold higher relative bioavailability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The optimized cubosomal system effectively improved the oral delivery and sustained release of DEM. The formulation demonstrated enhanced relative bioavailability and prolonged systemic exposure, supporting further development for oral DEM delivery. Anticoagulant efficacy, gastrointestinal safety, and appropriate dosing regimens remain to be established.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11095-026-04208-y","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:31:34Z","timestamp":1790281894000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Central Composite Design\u2013Optimized Dabigatran Etexilate Cubosomes for Sustained Oral Release and Enhanced In Vivo Pharmacokinetics"],"prefix":"10.1007","author":[{"given":"Aashka H.","family":"Bhatt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetal P.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvez S.","family":"Shaikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanshi R.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhrumi K.","family":"Naik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiren G.","family":"Rathod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavin A.","family":"Vyas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0374-2504","authenticated-orcid":false,"given":"Furqan A.","family":"Maulvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"issue":"5","key":"4208_CR1","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1161\/STROKEAHA.122.040073","volume":"54","author":"L Pu","year":"2023","unstructured":"Pu L, Wang L, Zhang R, Zhao T, Jiang Y, Han L. 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The study protocol was approved by the Institutional Animal Ethics Committee (IAEC) of Maliba Pharmacy College, Uka Tarsadia University, Bardoli, Surat, India (Protocol No: MPC\/IAEC\/32\/2024). All procedures were performed in compliance with relevant ethical regulations to minimize animal suffering and ensure humane handling.","order":1,"name":"Ethics","label":"Ethics Approval and Consent to Participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. This manuscript does not contain any studies involving human participants, human data, or identifiable personal information.","order":2,"name":"Ethics","label":"Consent for Publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"During the preparation of this manuscript, artificial intelligence (AI)\u2013assisted language tools were used solely to improve clarity, grammar, sentence structure, and overall readability of the text. The AI tools were not used for data analysis, data interpretation, generation of results, fabrication of content, image manipulation, or reference creation.","order":3,"name":"Ethics","label":"Use of Artificial Intelligence (AI) Tools","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The author(s) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}