{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:31:55Z","timestamp":1786437115353,"version":"build-2736575974"},"reference-count":19,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"publisher","award":["RGP2\/06\/47"],"award-info":[{"award-number":["RGP2\/06\/47"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RGP2\/06\/47"],"award-info":[{"award-number":["RGP2\/06\/47"]}],"id":[{"id":"https:\/\/ror.org\/052kwzs30","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Nanoemulsions are colloidal drug delivery systems consisting of an oil phase dispersed in water and stabilized by surfactants, producing droplets in the nanometer range. By virtue of their small droplet size and large interfacial area, they enhance drug dissolution, intestinal absorption, and site-specific delivery while offering controlled, prolonged release and a reduced risk of systemic side effects. Artemether (ART), an antimalarial agent, suffers from poor aqueous solubility and limited oral bioavailability, which restricts its therapeutic efficacy. Objective: The present study aimed to develop and optimize an Artemether-loaded nanoemulsion to improve the drug\u2019s dissolution rate and oral bioavailability. Methods: The nanoemulsion was formulated using a combination of Sunflower oil and Vippa oil as the oil phase, with Tween 80 and Span 80 as the surfactant system, and was prepared by an ultrasonication technique. A three-factor, three-level Box\u2013Behnken Design (BBD) was employed to systematically optimize the formulation composition and processing parameters. The formulations were evaluated for droplet size, polydispersity index (PDI), zeta potential, drug content, entrapment efficiency, pH, viscosity, refractive index, electrical conductivity, and cumulative in vitro drug release. Results: The optimized nanoemulsion exhibited a droplet size of 139.6 \u00b1 1.3 nm, a PDI of 0.256 \u00b1 0.03 indicating a narrow and uniform size distribution, and a zeta potential of \u221230.08 \u00b1 1.1 mV reflecting good physical stability. The formulation demonstrated a high entrapment efficiency of 95.42 \u00b1 1.18%, confirming efficient drug loading within the lipid core. Additional physicochemical evaluation revealed a pH of 6.4 \u00b1 0.2, a low viscosity of 2.84 \u00b1 0.15 cP, a refractive index of 1.338 \u00b1 0.002, and a conductivity of 215 \u00b1 12 \u00b5S\/cm, collectively confirming the formation of a physiologically compatible, isotropic oil-in-water nanoemulsion. The formulation achieved 97.90 \u00b1 0.97% cumulative in vitro drug release over a 12 h period, demonstrating a sustained release profile. Conclusions: The optimized Artemether-loaded nanoemulsion, developed using a Box\u2013Behnken Design, significantly enhanced the drug\u2019s dissolution and exhibited favorable physicochemical characteristics, high entrapment efficiency, and controlled release behavior. These findings suggest that nanoemulsion is a promising carrier system warranting further in vivo evaluation to confirm its potential for improving the oral bioavailability of Artemether.<\/jats:p>","DOI":"10.3390\/ph19081264","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:09:36Z","timestamp":1786435776000},"page":"1264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Formulation and Optimization of Artemether-Loaded Nanoemulsions by Applying QbD"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8368-9047","authenticated-orcid":false,"given":"Yahya","family":"Alhamhoom","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62223, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4643-0922","authenticated-orcid":false,"given":"Umme","family":"Hani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62223, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9419-4499","authenticated-orcid":false,"given":"Nagashubha","family":"Bobbarjang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Raghavendra Institute of Pharmaceutical Education and Research Campus, Ananthapuramu 515721, Andhra Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9404-5186","authenticated-orcid":false,"given":"Md Abdur","family":"Rashid","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62223, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhargav","family":"Eranti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Raghavendra Institute of Pharmaceutical Education and Research Campus, Ananthapuramu 515721, Andhra Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Battula","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Raghavendra Institute of Pharmaceutical Education and Research Campus, Ananthapuramu 515721, Andhra Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4819-6113","authenticated-orcid":false,"given":"Fahad","family":"AlQahtani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9478-9617","authenticated-orcid":false,"given":"Helal A.","family":"Helal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Vaggu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Raghavendra Institute of Pharmaceutical Education and Research Campus, Ananthapuramu 515721, Andhra Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maccha Kiran","family":"Sai","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Raghavendra Institute of Pharmaceutical Education and Research Campus, Ananthapuramu 515721, Andhra Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tadros, T.F. 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