{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T17:01:49Z","timestamp":1768928509288,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T00:00:00Z","timestamp":1616198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC \/ BIM-MET \/ 4447\/2014; POCI-01-0145-FEDER-016784"],"award-info":[{"award-number":["PTDC \/ BIM-MET \/ 4447\/2014; POCI-01-0145-FEDER-016784"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["MICINU, ref. RTI2018-093940-B-100"],"award-info":[{"award-number":["MICINU, ref. RTI2018-093940-B-100"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002911","name":"Universidad Complutense de Madrid","doi-asserted-by":"publisher","award":["Research Group 910939"],"award-info":[{"award-number":["Research Group 910939"]}],"id":[{"id":"10.13039\/501100002911","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The aim of this study was to develop multiparticulate systems with a combination of ezetimibe micellar systems and atorvastatin solid dispersions using croscarmellose as a hydrophilic vehicle and Kolliphor RH40 as a surfactant. The presence of a surfactant with low hydrophilic polymer ratios produces the rapid dissolution of ezetimibe through a drug\u2013polymer interaction that reduces its crystallinity. The solid dispersion of atorvastatin with low proportions of croscarmellose showed drug\u2013polymer interactions sufficient to produce the fast dissolution of atorvastatin. Efficacy studies were performed in diabetic Goto-Kakizaki rats with induced hyperlipidemia. The administration of multiparticulate systems of ezetimibe and atorvastatin at low (2 and 6.7 mg\/kg) and high (3 and 10 mg\/kg) doses showed similar improvements in levels of cholesterol, triglycerides, lipoproteins, alanine transaminase, and aspartate transaminase compared to the high-fat diet group. Multiparticulate systems at low doses (2 and 6.7 mg\/kg of ezetimibe and atorvastatin) had a similar improvement in hepatic steatosis compared to the administration of ezetimibe and atorvastatin raw materials at high doses (3 and 10 mg\/kg). These results confirm the effectiveness of solid dispersions with low doses of ezetimibe and atorvastatin to reduce high lipid levels and hepatic steatosis in diabetic rats fed a high-fat diet.<\/jats:p>","DOI":"10.3390\/pharmaceutics13030421","type":"journal-article","created":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T23:47:41Z","timestamp":1616370461000},"page":"421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Multiparticulate Systems of Ezetimibe Micellar System and Atorvastatin Solid Dispersion Efficacy of Low-Dose Ezetimibe\/Atorvastatin on High-Fat Diet-Induced Hyperlipidemia and Hepatic Steatosis in Diabetic Rats"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4123-3367","authenticated-orcid":false,"given":"Carlos","family":"Torrado-Salmer\u00f3n","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}]},{"given":"V\u00edctor","family":"Guarnizo-Herrero","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-7988","authenticated-orcid":false,"given":"Joana","family":"Henriques","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000\u2010548 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8378-0895","authenticated-orcid":false,"given":"Raquel","family":"Sei\u00e7a","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000\u2010548 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal"}]},{"given":"Cristina M.","family":"Sena","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000\u2010548 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3273-2615","authenticated-orcid":false,"given":"Santiago","family":"Torrado-Santiago","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"},{"name":"Instituto Universitario de Farmacia Industrial (IUFI), Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jbt.22295","article-title":"Protective effect of atorvastatin on oxidative stress in streptozotocin-induced diabetic rats independently their lipid-lowering effects","volume":"33","author":"Aktay","year":"2019","journal-title":"J. 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