{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T05:24:24Z","timestamp":1761110664949},"reference-count":21,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Objective Acute decompensated heart failure is often treated with a\n                    combination of loop and thiazide-like diuretics. Of these thiazide-like\n                    diuretics, two common choices are intravenous chlorothiazide or oral metolazone.\n                    Metolazone is more potent and has a longer duration of action, but since it is\n                    an oral formulation, it has a longer on-set time as compared to chlorothiazide.\n                    In addition, metolazone is poorly water-soluble, thereby rendering intravenous\n                    formulation more challenging. To address these issues, we proposed the\n                    formulation of a solvent-free metolazone emulsion for intravenous\n                    administration.<\/jats:p><jats:p>\n          Methods An oil-in-water emulsion containing 1\u2009mg\/mL of\n                    metolazone was formulated by homogenizing soybean oil and l-lecithin in\n                    water in the presence of optimized concentrations of glycerin with tween 80 or\n                    poloxamer 188 as surfactant. The emulsion was characterized on the basis of\n                    particle size, zeta potential, morphology and metolazone release kinetics. The\n                    diuretic effect of the metolazone emulsion was evaluated in rats.<\/jats:p><jats:p>\n          Results The 1\u2009mg\/mL metolazone emulsion prepared with\n                    5% tween 80 displayed the best physical stability. The emulsion\n                    exhibited a hydrodynamic diameter of 157.13\u00b11.52\u2009nm. About\n                    93% of metolazone was released from the formulation within 2\u2009h.\n                    The 2\u2009mg\/kg and 4\u2009mg\/kg dose of the metolazone\n                    emulsion increased urine output in the rats by 68.9 and 134%,\n                    respectively, as compared to control rats. Furthermore, the\n                    4\u2009mg\/kg dose exhibited a 168.8%, 25.8%, and\n                    150.9% increase in sodium, potassium, and chloride, respectively.<\/jats:p><jats:p>\n          Conclusion This metolazone emulsion was capable of increasing urine volume\n                    output and demonstrated both natriuretic and kaliuretic properties.<\/jats:p>","DOI":"10.1055\/a-1813-9489","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T22:36:19Z","timestamp":1652222179000},"page":"299-305","source":"Crossref","is-referenced-by-count":2,"title":["Formulation, Characterization, and the Diuretic Effects of a New\n                    Intravenous Metolazone Emulsion"],"prefix":"10.1055","volume":"72","author":[{"given":"Kristen M.","family":"Ahlschwede","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Rosalind\n                    Franklin University of Medicine and Science, North Chicago, IL,\n                    USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Ofori","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Chicago\n                    State University, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terrick","family":"Andey","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy,\n                    Massachusetts College of Pharmacy and Health Sciences, Worcester, MA,\n                    USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Osei","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Chicago\n                    State University, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John S","family":"Somberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rush University, Chicago, IL,\n                    USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"ref1","first-page":"510","article-title":"Acute decompensated heart failure: Contemporary medical management","volume":"36","author":"S M Joseph","year":"2009","journal-title":"Texas Hear Inst J"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/1755-5922.12109","article-title":"Comparison of Metolazone Versus Chlorothiazide in Acute Decompensated Heart\n                    Failure with Diuretic Resistance","volume":"33","author":"M P Moranville","year":"2015","journal-title":"Cardiovasc Ther"},{"key":"ref3","first-page":"e29","article-title":"Heart disease and stroke statistics-2015 update\u202f: A report from the American\n                    Heart Association","volume":"131","author":"D Mozaffarian","year":"2015","journal-title":"Circulation"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.jacc.2013.11.053","article-title":"The global health and economic burden of hospitalizations for heart failure:\n                    Lessons learned from hospitalized heart failure registries","volume":"63","author":"A P Ambrosy","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1161\/HHF.0b013e318291329a","article-title":"Forecasting the impact of heart failure in the united states a policy statement\n                    from the american heart association","volume":"6","author":"P A Heidenreich","year":"2013","journal-title":"Circ Hear Fail"},{"key":"ref6","first-page":"e391","article-title":"2009 focused update incorporated into the ACC\/AHA 2005 guidelines for\n                    the diagnosis and management of heart failure in adults: A report of the\n                    Aamerican College of Cardiology Foundation\/American Heart Association\n                    Task Force on practice guidelines: Developed in collaboration with the\n                    International Society for Heart and Lung Transplantation","volume":"119","author":"S A Hunt","year":"2009","journal-title":"Circulation"},{"key":"ref7","first-page":"e147","article-title":"2013 ACCF\/AHA guideline for the management of heart failure: A report of\n                    the American college of cardiology foundation\/american heart association\n                    task force on practice guidelines","volume":"62","author":"C W Yancy","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.cardfail.2010.04.004","article-title":"Heart Failure Society of America. 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