{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T20:21:42Z","timestamp":1757622102806,"version":"3.44.0"},"reference-count":20,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013688","name":"Minist\u00c3\u00a8re de l'\u00c3\u2030conomie, de l\u00e2\u20ac\u2122Innovation et des Exportations du Qu\u00c3\u00a9bec","doi-asserted-by":"publisher","award":["M\u00e9dicament Qu\u00e9bec RQM00158"],"award-info":[{"award-number":["M\u00e9dicament Qu\u00e9bec RQM00158"]}],"id":[{"id":"10.13039\/100013688","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>The Covid-19 pandemic has intensified shortages in various pharmaceutical products, notably injectable propofol in lipid emulsion form. Its demand surged sharply due to its critical role in intubating patients with respiratory distress during the pandemic, exposing vulnerabilities in the supply chain for this essential product.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>This project aims to develop an alternative formulation to commercially available propofol products and to evaluate its stability through a detailed study.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Two lipid emulsions commonly used for intravenous nutrition, Intralipid 20% and SMOFlipid 20%, were selected as diluents for pure propofol due to their composition\u2019s similarity to DIPRIVAN, the standard propofol product. We developed and validated an HPLC method for quantifying propofol and employed an optimized laser diffraction technique to measure particle size. Additionally, we assessed the pH of the formulations.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>The preparation method demonstrated repeatability and homogeneity. Stability studies revealed that the propofol concentrations remained close to the target of 10\u2009mg\/mL (1%). Although particle sizes were larger compared to DIPRIVAN, they were consistent with those of the lipid emulsions before propofol addition. The pH of the formulations remained stable throughout the study period.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The developed propofol emulsion formulations met USP standards for all tested parameters over a period of at least 7 days, indicating that these alternatives are a viable and stable substitute for commercial propofol products.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0331651","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T17:30:57Z","timestamp":1757352657000},"page":"e0331651","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Propofol emulsification in Intralipid and SMOFlipid: A promising alternative in response to future shortages"],"prefix":"10.1371","volume":"20","author":[{"given":"Maxime","family":"Murphy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Friciu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0790-5246","authenticated-orcid":true,"given":"Val\u00e9rie Ga\u00eblle","family":"Roullin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3087-2646","authenticated-orcid":true,"given":"Gr\u00e9goire","family":"Leclair","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"issue":"1","key":"pone.0331651.ref001","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cell.2018.08.031","article-title":"Propofol: Milk of Amnesia","volume":"175","author":"CT Walsh","year":"2018","journal-title":"Cell"},{"issue":"1","key":"pone.0331651.ref002","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13054-015-0772-5","article-title":"Propofol, midazolam, vancomycin and cyclosporine therapeutic drug monitoring in extracorporeal membrane oxygenation circuits primed with whole human blood","volume":"19","author":"F Lemaitre","year":"2015","journal-title":"Crit Care"},{"issue":"12","key":"pone.0331651.ref003","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1007\/s00134-020-06307-9","article-title":"Analgesia and sedation in patients with ARDS","volume":"46","author":"G Chanques","year":"2020","journal-title":"Intensive Care Med"},{"issue":"11","key":"pone.0331651.ref004","doi-asserted-by":"crossref","DOI":"10.1177\/03000605221138487","article-title":"Tracheotomy in ventilator-dependent patients with COVID-19: a cross-sectional study of analgesia and sedative requirements","volume":"50","author":"B Wiemann","year":"2022","journal-title":"J Int Med Res"},{"key":"pone.0331651.ref005","unstructured":"Intralipid. In: Fresenius Kabi Canada Lt\u00e9e. [Online]. Toronto, ON; 2017. Available from: https:\/\/pdf.hres.ca\/dpd_pm\/00039298.PDF"},{"key":"pone.0331651.ref006","unstructured":"SMOFlipid 20%. In:Fresenius Kabi Canada Lt\u00e9e. [Online]. Toronto, ON. 2018. Available from: https:\/\/www.fresenius-kabi.com\/en-ca\/documents\/SMOFlipid-ENG-PM-072923.pdf"},{"issue":"8","key":"pone.0331651.ref007","doi-asserted-by":"crossref","first-page":"999","DOI":"10.3109\/10837450.2013.840845","article-title":"Stability of parenteral nanoemulsions loaded with paclitaxel: the influence of lipid phase composition, drug concentration and storage temperature","volume":"19","author":"AN Kadam","year":"2014","journal-title":"Pharm Dev Technol"},{"issue":"5","key":"pone.0331651.ref008","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1080\/10837450.2020.1720237","article-title":"Development, characterization and stability evaluation of ciprofloxacin-loaded parenteral nutrition nanoemulsions","volume":"25","author":"A Said Suliman","year":"2020","journal-title":"Pharm Dev Technol"},{"issue":"5","key":"pone.0331651.ref009","first-page":"655","article-title":"The use of commercially available lipid emulsions for the preparation of amphotericin B-lipid admixtures","volume":"39","author":"Y Shadkhan","year":"1997","journal-title":"J Antimicrob Chemother"},{"issue":"5","key":"pone.0331651.ref010","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11046-009-9271-z","article-title":"Nystatin-intralipid preparation: characterization and in vitro activity against yeasts and molds","volume":"169","author":"R Semis","year":"2010","journal-title":"Mycopathologia"},{"issue":"3","key":"pone.0331651.ref011","doi-asserted-by":"crossref","first-page":"905","DOI":"10.3390\/pharmaceutics15030905","article-title":"Hospital production of sterile 2% propofol nanoemulsion: proof of concept","volume":"15","author":"A Cebe","year":"2023","journal-title":"Pharmaceutics"},{"key":"pone.0331651.ref012","doi-asserted-by":"crossref","first-page":"122960","DOI":"10.1016\/j.ijpharm.2023.122960","article-title":"Development of a compounded propofol nanoemulsion using multiple non-invasive process analytical technologies","volume":"640","author":"T Rooimans","year":"2023","journal-title":"Int J Pharm"},{"issue":"23","key":"pone.0331651.ref013","doi-asserted-by":"crossref","first-page":"7183","DOI":"10.3390\/molecules26237183","article-title":"Continuous Flow Synthesis of Propofol","volume":"26","author":"R Mougeot","year":"2021","journal-title":"Molecules"},{"key":"pone.0331651.ref014","article-title":"Uniformity of Dosage Units <905>.","volume-title":"USP\u2013NF","author":"USP","year":"2022"},{"key":"pone.0331651.ref015","article-title":"Globule size distribution in lipid injectable emulsions <729>.","volume-title":"USP\u2013NF","author":"USP","year":"2019"},{"volume-title":"Q2 (R1) Validation of Analytical Procedures: Text and Methodology","year":"2005","author":"ICH harmonized tripartite guidelines","key":"pone.0331651.ref016"},{"key":"pone.0331651.ref017","article-title":"Propofol.","volume-title":"USP\u2013NF","author":"USP","year":"2024"},{"key":"pone.0331651.ref018","article-title":"Propofol Injectable Emulsion.","volume-title":"USP\u2013NF","author":"USP","year":"2011"},{"issue":"7","key":"pone.0331651.ref019","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1002\/fsn3.1069","article-title":"Effect of storage temperature on lipid oxidation and changes in nutrient contents in peanuts","volume":"7","author":"K Liu","year":"2019","journal-title":"Food Sci Nutr"},{"issue":"1","key":"pone.0331651.ref020","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1186\/s13054-022-04194-8","article-title":"Hospital change to mixed lipid emulsion from soybean oil-based lipid emulsion for parenteral nutrition in hospitalized and critically ill adults improves outcomes: a pre-post-comparative study","volume":"26","author":"KL Haines","year":"2022","journal-title":"Crit Care"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331651","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T17:31:01Z","timestamp":1757352661000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331651"}},"subtitle":[],"editor":[{"given":"Giovanni","family":"Giordano","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,8]]},"references-count":20,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0331651","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2025,9,8]]}}}