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-11497755-B2
Publication Date
2022-11-15
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 invention relates to concentrated liquid pharmaceutical formulations comprising furosemide, or a pharmaceutically acceptable salt thereof, for liquid delivery, wherein the furosemide concentration is selected within defined ranges and the formulation is maintained at a specified pH. The formulations further comprise benzyl alcohol in an amount defined by weight percent, and a pharmaceutically acceptable buffer comprising tromethamine, or a pharmaceutically acceptable salt thereof, at a defined molarity range. The formulation is characterized by a pH between about 6.5 to about 8.5 and is isosmotic.
A central aspect of the invention is selecting tromethamine buffer concentration and formulation pH together with benzyl alcohol so that the furosemide can be provided at high concentrations in a single liquid formulation while maintaining isosmotic characteristics. The disclosed formulation ranges include furosemide concentrations from about 60 mg/mL to about 120 mg/mL, benzyl alcohol at about 0.5% (w/w) to about 5% (w/w), and tromethamine at about 25 mM to about 150 mM, with pH constrained to about 6.5 to about 8.5.
The disclosure additionally supports the formulation approach with solubility investigations showing how buffer type and pH affect furosemide solubility, and how excipients such as N-methyl-pyrrolidone and benzyl alcohol influence solubility trends under different buffering conditions. The document describes an example concentrated formulation including a specific combination of furosemide concentration, tromethamine buffering, and benzyl alcohol with an identified pH target, together with unit-dose or kit concepts and described administration targets including congestion, edema, fluid overload, and hypertension.
Claims Coverage
The partial content provides three independent claims, covering liquid pharmaceutical formulations with furosemide, benzyl alcohol, and a tromethamine buffer at defined concentration ranges and an isosmotic pH window, with narrower quantitative ranges in dependent claim sets.
Concentrated liquid formulation with tromethamine buffer
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; benzyl alcohol, wherein the amount of benzyl alcohol 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 150 mM; wherein the liquid pharmaceutical formulation has a pH of between about 6.5 to about 8.5, and is isosmotic.
Concentrated isosmotic formulation with narrowed component ranges
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; benzyl alcohol, wherein the amount of benzyl alcohol is from about 1% (w/w) to about 3.5% (w/w); and a pharmaceutically acceptable buffer comprising tromethamine or a pharmaceutically acceptable salt thereof, wherein the concentration of tromethamine is from about 50 mM to about 125 mM; wherein the liquid pharmaceutical formulation has a pH of between about 7 to about 8.5, and is isosmotic.
Isosmotic concentrated formulation with defined pH and component ranges
A liquid pharmaceutical formulation comprising furosemide, or a pharmaceutically acceptable salt thereof, wherein the concentration of furosemide is from about 80 mg/mL to about 100 mg/mL; benzyl alcohol, wherein the amount of benzyl alcohol is from about 1% (w/w) to about 3.5% (w/w); and a pharmaceutically acceptable buffer comprising tromethamine or a pharmaceutically acceptable salt thereof, wherein the concentration of tromethamine is from about 50 mM to about 125 mM; wherein the liquid pharmaceutical formulation has a pH of between about 7 to about 8, and is isosmotic.
Across the independent claims, the inventive coverage is directed to liquid pharmaceutical formulations that combine furosemide at defined high concentrations with benzyl alcohol and a tromethamine buffer at defined molarities, while maintaining the formulation as isosmotic within specified pH ranges. Dependent claims refine these ranges further and, in later dependents, characterize isosmotic behavior using osmolarity or osmolality ranges.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Subcutaneous administration and parenteral infusion/injection for congestion, edema, fluid overload, and hypertension.
Delivery concepts including on-body/wearable pump-patch delivery and micropump/patch device concepts.
Unit-dose/kit concepts for the concentrated liquid formulation.
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