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Methods: A face-centered central composite design combined with response surface methodology (FCCD-RSM) was utilized to assess the effects of the zeolite\/sodium alginate ratio, alginate concentration, calcium chloride concentration and curing time on the encapsulation efficiency (EE), sphericity factor (SF), and roundness (Rn). Results: The EE ranged from 5.9% to 91.3%, depending on the formulation composition. Numerical optimization identified the optimal conditions as 70.962% EE, 0.05 SF and 1.00 Rn, with a desirability score of 0.873. The incorporation of natural clinoptilolite improved microcapsule structural integrity and reduced the initial burst release by modulating diffusion pathways within the hybrid matrix. The optimized CNZ@AMOX exhibited pH-dependent release behavior, with minimal drug release in simulated gastric fluid (SGF) and diffusion-controlled release in simulated intestinal fluid (SIF), which was best described by the Korsmeyer\u2013Peppas model. Conclusions: These findings demonstrate that zeolite\u2013alginate hybrid microcapsules represent promising inorganic\u2013organic composite carriers for the pH-responsive and controlled delivery of AMOX.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070878","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:00:17Z","timestamp":1784548817000},"page":"878","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Clinoptilolite as a Functional Mineral Component in Alginate Hybrid Microcapsules for Controlled Amoxicillin Release"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9870-8514","authenticated-orcid":false,"given":"\u0130rem","family":"Toprak\u00e7\u0131","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, Faculty of Engineering, Istanbul University-Cerrahpa\u015fa, Avc\u0131lar, 34320 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2241-2562","authenticated-orcid":false,"given":"Ebru","family":"Kurtulba\u015f","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Faculty of Engineering, Istanbul University-Cerrahpa\u015fa, Avc\u0131lar, 34320 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4914-6986","authenticated-orcid":false,"given":"Dorina","family":"Simedru","sequence":"additional","affiliation":[{"name":"INCDO-INOE 2000, Research Institute for Analytical Instrumentation, 67 Donath Street, 400293 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Becze","sequence":"additional","affiliation":[{"name":"INCDO-INOE 2000, Research Institute for Analytical Instrumentation, 67 Donath Street, 400293 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0879-9211","authenticated-orcid":false,"given":"Oana","family":"Cadar","sequence":"additional","affiliation":[{"name":"INCDO-INOE 2000, Research Institute for Analytical Instrumentation, 67 Donath Street, 400293 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9989-9823","authenticated-orcid":false,"given":"Selin","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Faculty of Engineering, Istanbul University-Cerrahpa\u015fa, Avc\u0131lar, 34320 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.mattod.2023.01.002","article-title":"Oral drug delivery platforms for biomedical applications","volume":"62","author":"Ouyang","year":"2023","journal-title":"Mater. 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