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Taking heed of critical process parameters (CPPs) and critical material attributes (CMAs), a formulation capable of meeting the pre-defined Quality Target Product Profiles (QTPPs) and critical quality attributes (CQAs) was achieved. Delivering 50% of the Paracetamol (PAR) dose within the first 30\u00a0min, from an Immediate Release (IR) layer of 250\u00a0mg (PAR) for an early onset of analgesia; 100\u00a0mg of Diclofenac Sodium (DS) and 250\u00a0mg of PAR from the cup, formulated for a delayed and retarded release, and lastly 20\u00a0mg Esomeprazole Magnesium Trihydrate (ESM) from a press coated core pill, the latter often prescribed separately. The release mechanism of PAR and DS from the cup after the 2-h mark distinctly followed the Hixson-Crowell model where the geometrical characteristic of the cup was maintained with surface erosion. SEM analysis results prior to and during dissolution confirmed bulk and surface erosion release mechanisms. The obtained\n                    <jats:italic>ex vivo<\/jats:italic>\n                    analysis results showed retarded permeation rates of the tableted APIs compared to the APIs in their pure state.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1208\/s12249-025-03231-3","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T16:31:58Z","timestamp":1762446718000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Chrono-Prolific Controlled Release Tripartite Tablet: Case Study of Paracetamol, Diclofenac Sodium and Esomeprazole Magnesium Trihydrate"],"prefix":"10.1208","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3062-1946","authenticated-orcid":false,"given":"Kundai R.","family":"Mazarura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8640-4350","authenticated-orcid":false,"given":"Pradeep","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3868-1898","authenticated-orcid":false,"given":"Armorel","family":"van Eyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-1529","authenticated-orcid":false,"given":"Yahya E.","family":"Choonara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"3231_CR1","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1097\/j.pain.0000000000001844","volume":"161","author":"PR Kamerman","year":"2020","unstructured":"Kamerman PR, Bradshaw D, Laubscher R, Pillay-Van Wyk V, Gray GE, Mitchell D, et al. 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