Formulation, Characterization, and the Diuretic Effects of a New Intravenous Metolazone Emulsion.

Autor:	Ahlschwede KM; Department of Pharmaceutical Sciences, College of Pharmacy, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA., Ofori E; Department of Pharmaceutical Sciences, College of Pharmacy, Chicago State University, Chicago, IL, USA., Andey T; Department of Pharmaceutical Sciences, School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, Worcester, MA, USA., Osei A; Department of Pharmaceutical Sciences, College of Pharmacy, Chicago State University, Chicago, IL, USA., Somberg JS; Department of Medicine, Rush University, Chicago, IL, USA.
Jazyk:	angličtina
Zdroj:	Drug research [Drug Res (Stuttg)] 2022 Jul; Vol. 72 (6), pp. 299-305. Date of Electronic Publication: 2022 May 10.
DOI:	10.1055/a-1813-9489
Abstrakt:	Objective: Acute decompensated heart failure is often treated with a combination of loop and thiazide-like diuretics. Of these thiazide-like diuretics, two common choices are intravenous chlorothiazide or oral metolazone. Metolazone is more potent and has a longer duration of action, but since it is an oral formulation, it has a longer on-set time as compared to chlorothiazide. In addition, metolazone is poorly water-soluble, thereby rendering intravenous formulation more challenging. To address these issues, we proposed the formulation of a solvent-free metolazone emulsion for intravenous administration. Methods: An oil-in-water emulsion containing 1 mg/mL of metolazone was formulated by homogenizing soybean oil and l -lecithin in water in the presence of optimized concentrations of glycerin with tween 80 or poloxamer 188 as surfactant. The emulsion was characterized on the basis of particle size, zeta potential, morphology and metolazone release kinetics. The diuretic effect of the metolazone emulsion was evaluated in rats. Results: The 1 mg/mL metolazone emulsion prepared with 5% tween 80 displayed the best physical stability. The emulsion exhibited a hydrodynamic diameter of 157.13±1.52 nm. About 93% of metolazone was released from the formulation within 2 h. The 2 mg/kg and 4 mg/kg dose of the metolazone emulsion increased urine output in the rats by 68.9 and 134%, respectively, as compared to control rats. Furthermore, the 4 mg/kg dose exhibited a 168.8%, 25.8%, and 150.9% increase in sodium, potassium, and chloride, respectively. Conclusion: This metolazone emulsion was capable of increasing urine volume output and demonstrated both natriuretic and kaliuretic properties. Competing Interests: KMA has received grant funding from Academic Pharmaceuticals Inc. JCS has a financial interest in Academic Pharmaceuticals Inc. EO, AO, TA have no conflicts of interest. (Thieme. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu