{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:57:29Z","timestamp":1791302249209,"version":"4.1.0"},"reference-count":40,"publisher":"American Chemical Society (ACS)","issue":"39","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003032","name":"Association Nationale de la Recherche et de la Technologie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003032","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lipid-based formulations (LBFs) offer a promising strategy to enhance the oral bioavailability of poorly water-soluble drugs, such as biopharmaceutical classification system (BCS) Class IV compounds. However, their in vitro characterization remains challenging because of the complex interplay between dispersion, dissolution, lipid digestion, and absorption. In this study, several LBFs of ticagrelor were investigated using a progressive set of in vitro models of increasing physiological complexity, including dissolution testing in biorelevant media using USP II and USP IV apparatuses, intestinal and gastrointestinal lipolysis assays, and a dynamic gastrointestinal model (TIM-1). The aim of this study was to evaluate the capabilities and limitations of each method and examine how increasing model complexity and experimental setup influences formulation performance and relative ranking. The results showed that the formulation ranking was strongly method-dependent. Under biorelevant conditions, USP II and USP IV generated distinct release kinetics but similar rankings with minimal differences observed between the LBFs. In contrast, lipolysis experiments highlighted the impact of lipid digestion, with the inclusion of a gastric phase increasing intestinal drug availability. TIM-1 provided unique insights into LBF behavior under dynamic gastrointestinal conditions, capturing the combined effects of digestion, transit, and absorption. Overall, the observed model-dependent ranking emphasizes the importance of combining complementary in vitro approaches to achieve a mechanistic and robust characterization of lipid-based formulations and to support future IVIVC development.<\/jats:p>","DOI":"10.1021\/acsomega.6c08404","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T15:02:29Z","timestamp":1789916549000},"page":"60378-60387","source":"Crossref","is-referenced-by-count":0,"title":["The Role of In\nVitro Model Complexity in Lipid-Based\nFormulation Screening: A Case Study with Ticagrelor"],"prefix":"10.1021","volume":"11","author":[{"given":"Arnaud","family":"Bourderi-Cambon","sequence":"first","affiliation":[{"name":"Universite\u0301 Clermont Auvergne, UMR 454 MEDiS UCA-INRAE , ,","place":["Clermont-Ferrand, France, 63000"]},{"name":"Gattefosse\u0301 SAS , 36 Chemin de Genas , ,","place":["Saint-Priest, France, 69804"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Fadhlaoui","sequence":"additional","affiliation":[{"name":"Universite\u0301 Clermont Auvergne, UMR 454 MEDiS UCA-INRAE , ,","place":["Clermont-Ferrand, France, 63000"]},{"name":"Universite\u0301 Clermont Auvergne, UMR 6023 Laboratoire Microorganismes: Ge\u0301nome et Environnement CNRS-UCA , ,","place":["Clermont-Ferrand, France, 63000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Rossano","sequence":"additional","affiliation":[{"name":"Gattefosse\u0301 SAS , 36 Chemin de Genas , ,","place":["Saint-Priest, France, 69804"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Chalancon","sequence":"additional","affiliation":[{"name":"Universite\u0301 Clermont Auvergne, UMR 454 MEDiS UCA-INRAE , ,","place":["Clermont-Ferrand, France, 63000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathe\u0301rine","family":"Dhainaut","sequence":"additional","affiliation":[{"name":"Universite\u0301 Clermont Auvergne, UMR 454 MEDiS UCA-INRAE , ,","place":["Clermont-Ferrand, France, 63000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ste\u0301phanie","family":"Chevrier","sequence":"additional","affiliation":[{"name":"Gattefosse\u0301 SAS , 36 Chemin de Genas , ,","place":["Saint-Priest, France, 69804"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Schneider","sequence":"additional","affiliation":[{"name":"Gattefosse\u0301 SAS , 36 Chemin de Genas , ,","place":["Saint-Priest, France, 69804"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2748-7472","authenticated-orcid":true,"given":"Sylvain","family":"Denis","sequence":"additional","affiliation":[{"name":"Universite\u0301 Clermont Auvergne, UMR 454 MEDiS UCA-INRAE , ,","place":["Clermont-Ferrand, France, 63000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Caisse","sequence":"additional","affiliation":[{"name":"Gattefosse\u0301 SAS , 36 Chemin de Genas , ,","place":["Saint-Priest, France, 69804"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4690-4828","authenticated-orcid":true,"given":"Eric","family":"Beyssac","sequence":"additional","affiliation":[{"name":"Universite\u0301 Clermont Auvergne, UMR 454 MEDiS UCA-INRAE , ,","place":["Clermont-Ferrand, France, 63000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"issue":"3","key":"2026100610471767200_cit1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1023\/A:1016212804288","article-title":"A theoretical basis\nfor a biopharmaceutic drug classification: the correlation of in vitro\ndrug product dissolution and in vivo bioavailability","volume":"12","author":"Amidon","year":"1995","journal-title":"Pharm. Res."},{"issue":"1","key":"2026100610471767200_cit2","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3109\/21556660.2014.946604","article-title":"Absolute bioavailability and regional absorption of ticagrelor in\nhealthy volunteers","volume":"3","author":"Teng","year":"2014","journal-title":"J. Drug Assess."},{"issue":"9","key":"2026100610471767200_cit3","doi-asserted-by":"publisher","first-page":"10522","DOI":"10.1021\/acsomega.3c08700","article-title":"Preparation and Evaluation\nof a Self-Emulsifying Drug Delivery System for Improving the Solubility\nand Permeability of Ticagrelor","volume":"9","author":"Aziz","year":"2024","journal-title":"ACS Omega"},{"key":"2026100610471767200_cit4","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.2147\/IJN.S190426","article-title":"Strategic\napproach to developing a self-microemulsifying drug delivery\nsystem to enhance antiplatelet activity and bioavailability of ticagrelor","volume":"14","author":"Na","year":"2019","journal-title":"Int. J. Nanomed."},{"issue":"1","key":"2026100610471767200_cit5","doi-asserted-by":"publisher","first-page":"61","DOI":"10.2174\/2211738508666200708150151","article-title":"Formulation and In Vivo\nEvaluation of Ticagrelor Self-nanoemulsifying Drug Delivery Systems","volume":"9","author":"Aparna","year":"2021","journal-title":"Pharm. Nanotechnol."},{"issue":"9","key":"2026100610471767200_cit6","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1023\/A:1025718513246","article-title":"Intestinal\nlymphatic transport of halofantrine occurs after oral administration\nof a unit-dose lipid-based formulation to fasted dogs","volume":"20","author":"Khoo","year":"2003","journal-title":"Pharm. 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Ind. Pharm."},{"issue":"1","key":"2026100610471767200_cit33","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.ijpharm.2015.09.009","article-title":"Development of self\nemulsifying lipid formulations of BCS class II drugs with low to medium\nlipophilicity","volume":"495","author":"Jannin","year":"2015","journal-title":"Int. J. Pharm."},{"issue":"5","key":"2026100610471767200_cit34","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.bbalip.2007.02.009","article-title":"Comparative study on digestive lipase activities on\nthe self emulsifying excipient Labrasol, medium chain glycerides and\nPEG esters","volume":"1771","author":"Fernandez","year":"2007","journal-title":"Biochim. Biophys. Acta, Mol. Cell\nBiol. Lipids"},{"issue":"8","key":"2026100610471767200_cit35","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2026.104318","article-title":"Predicting\nsurfactant\neffects on drug permeation across hollow fiber membrane","volume":"115","author":"Patel","year":"2026","journal-title":"J. Pharm. Sci."},{"issue":"4","key":"2026100610471767200_cit36","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics18040400","article-title":"TIM-1\nand Tiny-TIM as Robust In Vitro Models for Oral\nBiopharmaceutics: Evidence from an International Ring Study","volume":"18","author":"O\u2019Farrell","year":"2026","journal-title":"Pharmaceutics"},{"key":"2026100610471767200_cit37","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.addr.2019.06.010","article-title":"In vitro digestion models to evaluate lipid based drug delivery\nsystems; present status and current trends","volume":"142","author":"Berthelsen","year":"2019","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026100610471767200_cit38","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ejpb.2020.01.010","article-title":"An in vitro dissolution\u2013digestion\u2013permeation\nassay for the study of advanced drug delivery systems","volume":"149","author":"Alvebratt","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"issue":"4","key":"2026100610471767200_cit39","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3390\/pharmaceutics13040489","article-title":"Estimating the Oral Absorption from\nSelf-Nanoemulsifying Drug Delivery Systems Using an In Vitro Lipolysis-Permeation\nMethod","volume":"13","author":"Klitgaard","year":"2021","journal-title":"Pharmaceutics"},{"key":"2026100610471767200_cit40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2024.125007","article-title":"Enhancing oral bioavailability\nof dasatinib via supersaturable SNEDDS:\nInvestigation of precipitation inhibition and IVIVC through in-vitro lipolysis-permeation model","volume":"668","author":"Mageshvaran","year":"2025","journal-title":"Int. J. Pharm."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c08404","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/39\/60378\/68567556\/acsomega.6c08404.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/39\/60378\/68567556\/acsomega.6c08404.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:23:45Z","timestamp":1791300225000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/39\/60378\/5433491\/The-Role-of-In-Vitro-Model-Complexity-in-Lipid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":40,"journal-issue":{"issue":"39","published-online":{"date-parts":[[2026,9,20]]},"published-print":{"date-parts":[[2026,10,6]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c08404","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}