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This work aims to delay the release of indomethacin (IND), a commonly used anti-inflammatory drug, using a pH-dependent polymer within orally disintegrating tablets (ODTs) and to investigate the effect of the polymer particle size on the ODTs. When developing delayed-release formulations for orally disintegrating tablets (ODTs), it's essential to balance the pellet's matrix properties to maintain integrity and delayed release. Different sizes of Eudragit L100 were used to create IND-containing pellets via extrusion spheronization, which were then embedded into the matrix of ODTs. The particle sizes displayed good elastic properties with low Young's modulus (YM) values, and there was no significant difference between the different sizes (45, 60, 93\u00a0\u00b5m; <jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). The tensile strength of the pellets was directly proportional to YM (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), providing enough support to maintain their integrity under compression. Pellets made from 63\u00a0\u00b5m Eudragit L100 had a suitable balance of mechanical and pharmaceutical properties compared to other sizes. 63\u00a0\u00b5m pellets had an aspect ratio of 1.49\u2009\u00b1\u20090.26 and 61% yield, while their ODTs showed a fast disintegration time of 14\u2009\u00b1\u20090.6\u00a0s, while modifying the drug release. Furthermore, IND exhibited modified release in acidic media (pH 1.2) and immediate release in buffer media (pH 6.8). Overall, protecting pellet integrity was crucial to delay release in acidic media and enable immediate release in alkaline media. The newly developed formulation will improve compliance and reduce side effects associated with IND and other irritant drugs particularly in elderly populations.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>\n          <jats:p>Graphical illustration for developing delayed release indomethacin loaded Eudragit L100 pellets embedded in orally disintegrating tablets\n<\/jats:p>","DOI":"10.1208\/s12249-025-03082-y","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T19:22:27Z","timestamp":1743016947000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Engineering pH-Dependent Orally Disintegrating Tablets for Modified Indomethacin Release: A Polymer-Based Approach"],"prefix":"10.1208","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4732-0880","authenticated-orcid":false,"given":"Nihad","family":"Al-hashimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9815-3720","authenticated-orcid":false,"given":"Eman Zmaily","family":"Dahmash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-471X","authenticated-orcid":false,"given":"Mouhamad","family":"Khoder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-7499","authenticated-orcid":false,"given":"Raid","family":"Alany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-0256","authenticated-orcid":false,"given":"Amr","family":"Elshaer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"3082_CR1","doi-asserted-by":"crossref","unstructured":"Emam Kassab, S. 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