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

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. An oil-in-water emulsion containing 1 mg/mL of metolazone was formulated by homogenizing soybean oil and 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. This metolazone emulsion was capable of increasing urine volume output and demonstrated both natriuretic and kaliuretic properties.

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Déclaration de conflit d'intérêts

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.