{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:32:09Z","timestamp":1791829929410,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014882","name":"Australian Prostate Cancer","doi-asserted-by":"crossref","award":["QA25111"],"award-info":[{"award-number":["QA25111"]}],"id":[{"id":"10.13039\/100014882","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Lipid-based formulations are widely used to enhance the oral bioavailability of poorly water-soluble drugs. However, for weakly basic drugs with higher solubility under acidic conditions, precipitation and recrystallisation after gastric emptying can compromise a formulation\u2019s ability to maintain the drug in a solubilised, absorbable state. To address this, we evaluated an enteric coating strategy to preserve the biopharmaceutical performance of a silica-solidified lipid-based formulation. Methods and Results: The model weakly basic BCS Class IV drug, abiraterone acetate, was loaded into a lipid-based formulation and solidified using mesoporous silica nanoparticles. In an in vitro lipolysis model, introducing the formulation only after the onset of the intestinal phase led to lower precipitation and over 50% greater drug presence in the aqueous phase compared to a two-stage gastric\u2013intestinal digestion. In an in vivo pharmacokinetic study in Sprague Dawley rats, the silica\u2013lipid formulation (6 mg\/kg), delivered in gelatine minicapsules enteric-coated with Eudragit L100-55, resulted in a 2.6-fold higher systemic exposure compared to the non-coated formulation (p &lt; 0.0001). Conclusions: These findings support the use of enteric coating for lipid-based formulations and silica nanoparticles containing weakly basic drugs as a strategy to maintain formulation integrity until reaching the small intestine.<\/jats:p>","DOI":"10.3390\/pharmaceutics17101289","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T08:20:28Z","timestamp":1759393228000},"page":"1289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Enteric Coating Enhances the Biopharmaceutical Performance of a Silica\u2013Lipid Formulation of Abiraterone Acetate"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-2383","authenticated-orcid":false,"given":"Ali","family":"Taheri","sequence":"first","affiliation":[{"name":"Centre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6911-4562","authenticated-orcid":false,"given":"Ruba","family":"Almasri","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Wignall","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Feltrin","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7633-0562","authenticated-orcid":false,"given":"Kristen E.","family":"Bremmell","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-7901","authenticated-orcid":false,"given":"Paul","family":"Joyce","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5401-7535","authenticated-orcid":false,"given":"Clive A.","family":"Prestidge","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1016\/j.apsb.2022.02.025","article-title":"Current approaches of nanomedicines in the market and various stage of clinical translation","volume":"12","author":"Shan","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s13346-021-00908-7","article-title":"Current approaches in lipid-based nanocarriers for oral drug delivery","volume":"11","author":"Lozano","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejps.2013.04.002","article-title":"Biopharmaceutical classification of poorly soluble drugs with respect to \u201cenabling formulations\u201d","volume":"50","author":"Buckley","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1007\/s11095-013-1229-7","article-title":"Recent advances in lipid-based formulation technology","volume":"30","author":"Porter","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ijpharm.2013.03.054","article-title":"Lipid-based formulations for oral administration of poorly water-soluble drugs","volume":"453","author":"Mu","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/s41578-021-00385-x","article-title":"Clinical translation of silica nanoparticles","volume":"6","author":"Janjua","year":"2021","journal-title":"Nat. Rev. Mater."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115115","DOI":"10.1016\/j.addr.2023.115115","article-title":"Silica nanoparticles: A review of their safety and current strategies to overcome biological barriers","volume":"203","author":"Janjua","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1080\/03639045.2018.1542709","article-title":"Enhancing oral bioavailability of poorly soluble drugs with mesoporous silica based systems: Opportunities and challenges","volume":"45","author":"Bremmell","year":"2019","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"123946","DOI":"10.1016\/j.ijpharm.2024.123946","article-title":"High loading of lipophilic compounds in mesoporous silica for improved solubility and dissolution performance","volume":"654","author":"Brenner","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106132","DOI":"10.1016\/j.ejps.2022.106132","article-title":"Inhibition of celecoxib crystallization by mesoporous silica\u2013Molecular dynamics studies leading to the discovery of the stabilization origin","volume":"171","author":"Kramarczyk","year":"2022","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.addr.2018.11.006","article-title":"Solidification to improve the biopharmaceutical performance of SEDDS: Opportunities and challenges","volume":"142","author":"Joyce","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105640","DOI":"10.1016\/j.ejps.2020.105640","article-title":"The influence of solidification on the in vitro solubilisation of blonanserin loaded supersaturated lipid-based oral formulations","volume":"157","author":"Schultz","year":"2021","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11095-020-02795-y","article-title":"Supersaturated-silica lipid hybrids improve in vitro solubilization of abiraterone acetate","volume":"37","author":"Schultz","year":"2020","journal-title":"Pharm. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Almasri, R., Joyce, P., Schultz, H.B., Thomas, N., Bremmell, K.E., and Prestidge, C.A. (2020). Porous nanostructure, lipid composition, and degree of drug supersaturation modulate in vitro fenofibrate solubilization in silica-lipid hybrids. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070687"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1124\/jpet.118.254466","article-title":"Supersaturated silica-lipid hybrid oral drug delivery systems: Balancing drug loading and in vivo performance","volume":"370","author":"Schultz","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105357","DOI":"10.1016\/j.ejps.2020.105357","article-title":"Enhancing the oral bioavailability of simvastatin with silica-lipid hybrid particles: The effect of supersaturation and silica geometry","volume":"150","author":"Meola","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1021\/acs.molpharmaceut.1c00781","article-title":"Role of Silica Intrawall Microporosity on Abiraterone acetate solubilization and in vivo oral absorption","volume":"19","author":"Almasri","year":"2022","journal-title":"Mol. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1007\/s13346-020-00853-x","article-title":"A safety, tolerability, and pharmacokinetic study of a novel simvastatin silica-lipid hybrid formulation in healthy male participants","volume":"11","author":"Meola","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s13346-013-0172-9","article-title":"First in man bioavailability and tolerability studies of a silica\u2013lipid hybrid (Lipoceramic) formulation: A Phase I study with ibuprofen","volume":"4","author":"Tan","year":"2014","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jconrel.2013.01.012","article-title":"Silica\u2013lipid hybrid (SLH) formulations enhance the oral bioavailability and efficacy of celecoxib: An in vivo evaluation","volume":"167","author":"Nguyen","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1007\/s40262-023-01266-y","article-title":"Unraveling complexities in the absorption and Disposition Kinetics of Abiraterone via Iterative PBPK Model Development and Refinement","volume":"62","author":"Cheong","year":"2023","journal-title":"Clin. Pharmacokinet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Taheri, A., Almasri, R., Wignall, A., Schultz, H.B., Elz, A.S., Ariaee, A., Bremmell, K.E., Joyce, P., and Prestidge, C.A. (2024). Enhancing the pharmacokinetics of abiraterone acetate through lipid-based formulations: Addressing solubility and food effect challenges. Drug Deliv. Transl. Res.","DOI":"10.1007\/s13346-024-01755-y"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1007\/s13346-024-01657-z","article-title":"Exploration of Abiraterone acetate loaded Nanostructured lipid carriers for bioavailability improvement and circumvention of fast-fed variability","volume":"15","author":"Shah","year":"2025","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"119069","DOI":"10.1016\/j.ijpharm.2020.119069","article-title":"Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate","volume":"577","author":"Schultz","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"119264","DOI":"10.1016\/j.ijpharm.2020.119264","article-title":"Enhancement of abiraterone acetate oral bioavailability by supersaturated-silica lipid hybrids","volume":"582","author":"Schultz","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ejps.2012.11.004","article-title":"Oral bioavailability of cinnarizine in dogs: Relation to SNEDDS droplet size, drug solubility and in vitro precipitation","volume":"48","author":"Larsen","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_27","first-page":"1","article-title":"Enteric targeting through enteric coating","volume":"115","author":"Brogmann","year":"2001","journal-title":"Drugs Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1021\/la500094b","article-title":"The role of porous nanostructure in controlling lipase-mediated digestion of lipid loaded into silica particles","volume":"30","author":"Joyce","year":"2014","journal-title":"Langmuir"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1700213","DOI":"10.1002\/ejlt.201700213","article-title":"Modulating the Lipase-Mediated Bioactivity of Particle-Lipid Conjugates Through Changes in Nanostructure and Surface Chemistry","volume":"119","author":"Joyce","year":"2017","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10198","DOI":"10.1021\/acs.langmuir.5b02476","article-title":"QCM-D and ToF-SIMS investigation to deconvolute the relationship between lipid adsorption and orientation on lipase activity","volume":"31","author":"Joyce","year":"2015","journal-title":"Langmuir"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.colsurfb.2016.02.059","article-title":"Orientating lipase molecules through surface chemical control for enhanced activity: A QCM-D and ToF-SIMS investigation","volume":"142","author":"Joyce","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejpb.2015.01.001","article-title":"Rapid conversion of the ester prodrug abiraterone acetate results in intestinal supersaturation and enhanced absorption of abiraterone: In vitro, rat in situ and human in vivo studies","volume":"90","author":"Stappaerts","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3109\/00498254.2012.721022","article-title":"A phase I, open-label, single-dose, mass balance study of 14C-labeled abiraterone acetate in healthy male subjects","volume":"43","author":"Acharya","year":"2013","journal-title":"Xenobiotica"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ejps.2010.09.002","article-title":"Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica","volume":"41","author":"Mellaerts","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.fjps.2017.02.001","article-title":"Pharmaceutical significance of Eudragit: A review","volume":"3","author":"Patra","year":"2017","journal-title":"Future J. Pharm. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1021\/acs.molpharmaceut.2c00895","article-title":"Impact of gastric pH variations on the release of amorphous solid dispersion formulations containing a weakly basic drug and enteric polymers","volume":"20","author":"Nguyen","year":"2023","journal-title":"Mol. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"123139","DOI":"10.1016\/j.ijpharm.2023.123139","article-title":"Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release","volume":"642","author":"Nguyen","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Qin, Y., Xiao, C., Li, X., Huang, J., Si, L., and Sun, M. (2022). Enteric polymer\u2013based amorphous solid dispersions enhance oral absorption of the weakly basic drug Nintedanib via stabilization of Supersaturation. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091830"},{"key":"ref_39","unstructured":"Angi, R., Jord\u00e1n, T., Basa-D\u00e9nes, O., Solymosi, T., \u00d6tv\u00f6s, Z., Glavinas, H., and Filipcsei, G. (2020). Complexes of abiraterone acetate, process for the preparation thereof and pharmaceutical compositions containing them. (No. 10,668,016), U.S. Patent."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105108","DOI":"10.1016\/j.jddst.2023.105108","article-title":"The combinative strategy for improving the intestinal stability and cellular absorption of curcumin by enteric coating of the optimized nanostructured lipid carriers","volume":"89","author":"Won","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hosny, K.M. (2016). Alendronate sodium as enteric coated solid lipid nanoparticles; preparation, optimization, and in vivo evaluation to enhance its oral bioavailability. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154926"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.intimp.2018.11.041","article-title":"Chylomicron mimicking solid lipid nanoemulsions encapsulated enteric minicapsules targeted to colon for immunization against hepatitis B","volume":"66","author":"Sahu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.2147\/IJN.S183479","article-title":"Solid lipid nanoparticles with enteric coating for improving stability, palatability, and oral bioavailability of enrofloxacin","volume":"14","author":"Li","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, K., Liu, W., Dong, Z., Zhang, L., Li, Q., Zhang, R., He, H., Lu, Y., Wu, W., and Qi, J. (2023). Translation of ionic liquids to be enteric nanoparticles for facilitating oral absorption of cyclosporine A. Bioeng. Transl. Med., 8.","DOI":"10.1002\/btm2.10405"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/s41565-024-01754-7","article-title":"A translational framework to DELIVER nanomedicines to the clinic","volume":"19","author":"Joyce","year":"2024","journal-title":"Nat. Nanotechnol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/10\/1289\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T04:17:35Z","timestamp":1759551455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/10\/1289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["pharmaceutics17101289"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17101289","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,2]]}}}