Concentrated liquid pharmaceutical formulations of furosemide
Inventors
Grossi, Alfredo • KOSTRABA, BRITT • OGUNLEYE, OLATOKUMBO O. LUCA • Terry, Shannon • KOPPENHAGEN, Franciscus
Assignees
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Publication Number
US-11571434-B2
Publication Date
2023-02-07
Expiration Date
Abstract
Disclosed herein, in part, are liquid pharmaceutical formulations comprising furosemide or a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable excipients, and a pharmaceutically acceptable buffer. Methods of treating congestion, edema, fluid overload, or hypertension in a patient in need thereof are also provided.
Core Innovation
The disclosed invention relates to concentrated liquid and unit liquid formulations of furosemide for parenteral and subcutaneous administration. The formulations include furosemide, or a pharmaceutically acceptable salt thereof, together with pharmaceutically acceptable excipients and a pharmaceutically acceptable buffer comprising tromethamine.
The furosemide concentration is defined within specified ranges and is intended to provide a concentrated liquid formulation. The formulations further include one or more pharmaceutically acceptable excipients in defined amounts and a buffer comprising tromethamine, or a pharmaceutically acceptable salt thereof, to maintain a target pH.
The pH is defined within a range that includes embodiments down to about 5.5. The disclosure includes embodiments where combinations of tromethamine with N-methyl-pyrrolidone and benzyl alcohol increase furosemide solubility to about 210 mg/mL at pH 7.4, and the invention centers on furosemide concentration, excipient selection, and a tromethamine buffer controlling pH and solubility.
Claims Coverage
The independent claims cover liquid pharmaceutical formulations having furosemide, or its pharmaceutically acceptable salt, at specified concentrations, pharmaceutically acceptable excipients at specified w/w amounts, and a tromethamine buffer at specified concentrations, with the formulation having a defined pH window. Across the independent claims, the inventive features are concentrated in three quantitative formulation sets and their pH limitations.
Concentrated furosemide liquid formulation with tromethamine buffer and controlled pH
A liquid pharmaceutical formulation comprising furosemide, or a pharmaceutically acceptable salt thereof, wherein the concentration of furosemide is from about 60 mg/mL to about 200 mg/mL; one or more pharmaceutically acceptable excipients, wherein the amount of the one or more pharmaceutically acceptable excipients is from about 0.1% (w/w) to about 30% (w/w); and a pharmaceutically acceptable buffer comprising tromethamine or a pharmaceutically acceptable salt thereof, wherein the concentration of tromethamine is from about 25 mM to about 150 mM; wherein the liquid pharmaceutical formulation has a pH of between about 6.5 to about 8.5.
Concentrated furosemide liquid formulation with narrower excipient and pH window
A liquid pharmaceutical formulation comprising furosemide, or a pharmaceutically acceptable salt thereof, wherein the concentration of furosemide is from about 60 mg/mL to about 120 mg/mL; one or more pharmaceutically acceptable excipients, wherein the amount of the one or more pharmaceutically acceptable excipients is from about 0.1% (w/w) to about 10% (w/w); and a pharmaceutically acceptable buffer comprising tromethamine or a pharmaceutically acceptable salt thereof, wherein the concentration of tromethamine is from about 25 mM to about 125 mM; wherein the liquid pharmaceutical formulation has a pH of between about 7 to about 8.5.
Higher-concentration furosemide liquid formulation with limited excipient amount and pH window
A liquid pharmaceutical formulation comprising furosemide, or a pharmaceutically acceptable salt thereof, wherein the concentration of furosemide is from about 70 mg/mL to about 100 mg/mL; one or more pharmaceutically acceptable excipients, wherein the amount of the one or more pharmaceutically acceptable excipients is from about 0.5% (w/w) to about 5% (w/w); and a pharmaceutically acceptable buffer comprising tromethamine or a pharmaceutically acceptable salt thereof, wherein the concentration of tromethamine is from about 25 mM to about 125 mM; wherein the liquid pharmaceutical formulation has a pH of between about 7 to about 8.5.
The independent claims define concentrated furosemide liquid formulations by combining specified furosemide concentration ranges, specified amounts of pharmaceutically acceptable excipients, and a tromethamine-containing buffer at specified mM levels, while constraining the formulation pH to defined ranges. Dependent claims further narrow quantitative ranges and identify particular excipient selections and optional additives such as water, an osmolarity adjuster, and a pH adjuster.
Stated Advantages
Documented Applications
No documented applications found
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