{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:00:57Z","timestamp":1790226057107,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Solid self-nanoemulsifying drug delivery systems (SNEDDS) prepared by adsorption onto porous carriers are widely used to improve the oral delivery of poorly water-soluble drugs. However, this approach is limited by increased dosing volume and incomplete drug release. This study aims to develop a thermoresponsive in situ salified SNEDDS (T-IS-SNEDDS) that simultaneously prevents formulation leakage and overcomes the release limitations of conventional adsorption-based solidification. Methods: Excipients were selected by solubility screening of oils and surfactants. Sodium and calcium carbonate were evaluated for in situ salt formation. Adsorption-based solid SNEDDS and thermoresponsive formulations containing poloxamer 188 with propylene glycol or polyethylene glycol 400 were prepared. Droplet size was measured after aqueous dilution. Solid-state characterization used scanning electron microscopy, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry, and powder X-ray diffraction. In vitro dissolution performance was evaluated against the raw drug and adsorption-based formulations. Results: Imwitor 308 and Tween 80 exhibited the highest solubilization capacities. Sodium carbonate (10 mg\/g) markedly increased the solubility of olmesartan medoxomil from 4.11 \u00b1 0.11 to 46.01 \u00b1 1.92 mg\/g. Although liquid in situ salified SNEDDS achieved rapid dissolution (94.2 \u00b1 1.8% at 10 min), adsorption-based solidification required four capsules and yielded incomplete drug release (67.76 \u00b1 3.18%). Both thermoresponsive formulations accommodated the therapeutic dose in a single capsule and released \u224895% of the drug within 60 min. Conclusions: The combined in situ salified drug loading and thermoresponsive matrix strategy successfully enables single capsule administration while overcoming the incomplete release of adsorption-based solid SNEDDS.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091195","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:06:51Z","timestamp":1790006811000},"page":"1195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Thermoresponsive In Situ Salified Self-Nanoemulsifying Drug Delivery System of Olmesartan Medoxomil: Overcoming Leakage and Drug Trapping Limitations"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1842-6010","authenticated-orcid":false,"given":"Abdelrahman Y.","family":"Sherif","sequence":"first","affiliation":[{"name":"Kayyali Research Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4877-864X","authenticated-orcid":false,"given":"Mohammad A.","family":"Altamimi","sequence":"additional","affiliation":[{"name":"Kayyali Research Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5177-4477","authenticated-orcid":false,"given":"Ehab M.","family":"Elzayat","sequence":"additional","affiliation":[{"name":"Kayyali Research Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v25.i1.20","article-title":"Solid self-nanoemulsifying delivery systems as a platform technology for formulation of poorly soluble drugs","volume":"25","author":"Bansal","year":"2008","journal-title":"Crit. 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