Liquid pharmaceutical formulations of loop diuretics and methods of administering same

Abstract

Disclosed herein, in part, are liquid pharmaceutical formulations and unit liquid pharmaceutical formulations comprising a loop diuretic and a pharmaceutically acceptable excipient. In certain embodiments, the formulations include a buffer and / or an antioxidant. Methods of treating congestion, edema, fluid overload, or hypertension in a patient in need thereof are also provided.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 376,157, filed September 19, 2022, the contents of which are incorporated herein in their entirety. [Background technology]

[0002] Loop diuretics can be used to treat hypertension, edema, and related conditions, such as congestive heart failure. For example, furosemide is commonly used to treat and / or manage edema associated with congestive heart failure, liver failure, and renal disease. H. Bundgaard, T. Norgaard, N. M. Nielsen, "Photodegradation and hydrolysis of furosemide and furosemide esters in aqueous solutions," International Journal of Pharmaceutics 42, 217 (1988).

[0003] The oral bioavailability, and therefore oral efficacy, of loop diuretics such as furosemide is often limited. Furosemide is commonly administered both parenterally and orally; however, significant variability in oral absorption is observed due to the combined effects of limited solubility and reduced stability at acidic pH. (B. Devarakonda, D.P. Otto, A. Judefeind, R.A. Hill, and M.M. de Villiers, "Effect of pH on the solubility and release of furosemide from polyamidoamine (PAMAM) dendrimer complexes," International Journal of Pharmaceutics 345, 142 (Dec. 10, 2007). Therefore, furosemide is typically administered intravenously or intramuscularly for most patients with congestive heart failure or other forms of more advanced edema.

[0004] Intravenous administration of medications such as loop diuretics requires trained medical professionals to place a catheter and administer the medication. In contrast, medications can be administered by subcutaneous injection or infusion, e.g., at home, by the patient or caregiver using an automatic injection device and / or a wearable, body-worn delivery and infusion device. Subcutaneous administration of loop diuretics by the patient or caregiver can also enable more optimal therapeutic dosing and total dose to produce more favorable pharmacokinetic and pharmacodynamic profiles and patient outcomes.

[0005] For subcutaneous administration, discomfort and pain should be minimized during administration to avoid decreased patient compliance with the treatment regimen. Factors that may contribute to the pain and discomfort experienced by the patient during, during, or after subcutaneous administration include the injection volume, the pH of the formulation, and the osmoticity or isotonicity of the formulation. Furthermore, such formulations should be stable in solution so that they can be rapidly utilized and / or pre-loaded into a wide variety of drug delivery devices.

[0006] Thus, there is a need for improved pharmaceutical formulations containing a loop diuretic (e.g., bumetanide, furosemide, or torsemide) that are chemically and physically stable over their useful life, contain a sufficient concentration of the loop diuretic (e.g., a therapeutically effective amount in an appropriate volume), and are at an appropriate pH and osmolality to allow, for example, subcutaneous administration of the loop diuretic. Summary of the Invention

[0007] In one aspect, the present invention provides a liquid pharmaceutical formulation of a loop diuretic (e.g., bumetanide, furosemide, or torsemide), eg, a loop diuretic, and a pharmaceutically acceptable excipient.

[0008] In various embodiments of the present invention, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of a loop diuretic, such as furosemide, or a pharmaceutically acceptable salt thereof; (ii) antioxidants, and (iii) a pharmaceutically acceptable buffer.

[0009] In another aspect, the present invention provides a unit liquid pharmaceutical formulation of a loop diuretic, such as furosemide, or a pharmaceutically acceptable salt thereof.

[0010] In various embodiments of the present invention, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 0.1% (w / w) to about 30% (w / w) of one or more pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and any combination thereof; (iii) about 0.05% (w / w) to about 2% (w / w) of an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, EDTA, and combinations thereof; and (iv) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and any combination thereof; The pH of the liquid pharmaceutical formulation is about 6.5 to about 8.5.

[0011] Another aspect of the present invention provides a method of treating congestion, edema, fluid overload, or hypertension in a patient in need thereof, the method comprising administering to the patient a liquid pharmaceutical formulation or unit liquid pharmaceutical formulation described herein.

[0012] Another aspect of the present invention provides a kit for the treatment of congestion, edema, fluid overload, or hypertension comprising a liquid pharmaceutical formulation, or a unit liquid pharmaceutical formulation, as described herein, and a delivery device (e.g., a pump device, an autoinjector, etc.), along with instructions for use. DETAILED DESCRIPTION OF THE INVENTION

[0013] The present invention provides liquid pharmaceutical formulations and unit liquid pharmaceutical formulations containing a loop diuretic (e.g., bumetanide, furosemide, or torsemide), medical kits containing the same, and methods of using the liquid pharmaceutical formulations and unit liquid pharmaceutical formulations to treat a medical disorder, e.g., congestion, edema, fluid overload, or hypertension, in a patient in need thereof. In particular, the present invention can provide pharmaceutical formulations of a loop diuretic that include pharmaceutically acceptable excipients, such as antioxidants, pH adjusters, solubilizers, osmolality adjusters, and / or pharmaceutically acceptable buffers, for administration to a patient.

[0014] definition To facilitate the understanding of this invention, several terms and phrases are defined below.

[0015] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. Abbreviations used herein have their conventional meaning in the chemical and biological arts. The chemical structures and formulas described herein are constructed according to the standard rules of chemical valency known in the chemical arts.

[0016] As used herein, the terms "a" and "an" mean "one or more" and include the plural forms unless the context requires otherwise.

[0017] In this application, when an element or component is described as being included in and / or selected from a list of described elements or components, it is to be understood that such element or component can be any of the described elements or components, and that such element or component can be selected from a group consisting of two or more of the described elements or components.

[0018] Furthermore, it should be understood that elements and / or features of the compositions or methods described herein, whether expressly or implied herein, can be combined in various manners without departing from the spirit and scope of the invention. For example, when a particular compound is referenced, that compound can be used in various embodiments of the compositions of the invention and / or methods of the invention, unless otherwise understood from the context. In other words, although embodiments are described and illustrated within this application so that the application is written and depicted concisely and clearly, it is intended and understood that the embodiments can be combined or separated in various ways without departing from the present teachings and invention(s). For example, it will be recognized that all features described and illustrated herein are applicable to all aspects of the invention(s) described and illustrated herein.

[0019] The phrase "at least one of" should be understood to include the object(s) described after such phrase and each of the various combinations of two or more of the described object(s) individually, unless otherwise understood from context and usage. The phrase "and / or" in the context of more than two described object(s) should be understood to have the same meaning, unless otherwise understood from context.

[0020] Use of the terms "include," "includes," "including," "have," "has," "having," "contain," "contains," or "containing," including their grammatical equivalents, generally, unless specifically stated or understood otherwise from the context, should be understood as open-ended and non-limiting, i.e., not excluding additional, unrecited elements or steps.

[0021] When the term "about" is used before a quantitative value, the present invention also includes that particular quantitative value itself unless specifically stated otherwise. As used herein, the term "about" refers to a ±10%, ±5%, ±3%, ±2%, or ±1% variation from the nominal value, unless otherwise indicated or inferred from the context.

[0022] At various places herein, values ​​are disclosed in groups or ranges. It is specifically intended that such descriptions include any and all individual subcombinations of the members of such groups and ranges. For example, an integer in the range of 0 to 40 is specifically intended to individually disclose 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, and 40, and an integer in the range of 1 to 20 is specifically intended to individually disclose 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20.

[0023] Any examples or use of exemplary language herein, such as "such as" or "including," are intended solely to better describe the invention and do not pose a limitation on the scope of the invention unless claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0024] As used herein, "compound" (including specifically named compounds, e.g., furosemide, bumetanide, ethacrynic acid, torsemide) refers to the compound per se and pharmaceutically acceptable salts thereof, unless otherwise understood from the context of the description or unless expressly limited to a particular form of the compound, e.g., the compound per se or a pharmaceutically acceptable salt thereof.

[0025] As used herein, "furosemide" refers to a compound of the formula: [ka] a compound having and its pharmaceutically acceptable salts. Such salts may include, but are not limited to, furosemide sodium salt and quaternary ammonium salts of furosemide. Furosemide may also be referred to by other names, such as frusemide, 5-(aminosulfonyl)-4-chloro-2-[(2-furanyl-methyl)amino]benzoic acid, its IUPAC name 4-chloro-2-(furan-2-ylmethylamino)-5-sulfamoylbenzoic acid, or its generic trade name Lasix®.

[0026] As used herein, "bumetanide" refers to a compound of the formula: [ka] a compound having and its pharmaceutically acceptable salts. Such salts may include, but are not limited to, furosemide potassium salt and furosemide sodium salt. Bumetanide may also be referred to by other names, such as bumetanide, bumetanide, its IUPAC name 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid, or its generic trade names Bumex® and Burinex®.

[0027] As used herein, "ethacrynic acid" refers to a compound of the formula: [ka] a compound having and its pharmaceutically acceptable salts. Such salts may include, but are not limited to, ethacrynic acid sodium salt (also called sodium ethacrynate). Ethacrynic acid may also be referred to by other names, such as ethacrynic acid, its IUPAC name 2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetic acid, or its generic trade names Sodium Edecrin® and Edecrin®.

[0028] As used herein, "torsemide" refers to a compound of the formula: [ka] a compound having and pharmaceutically acceptable salts thereof. Such salts may include, but are not limited to, torsemide sodium salt. Torsemide may also be referred to by other names, such as torasemide, 1-isopropyl-3-((4-(3-methylphenylamino)pyridine)-3-sulfonyl)urea, 1-isopropyl-3-((4-m-toluidino-3-pyridyl)sulfonyl)urea, its IUPAC name 1-[4-(3-methylanilino)pyridin-3-yl]sulfonyl-3-propan-2-ylurea, or its generic trade name Demadex®.

[0029] As used herein, the terms "subject" and "patient" refer to an organism treated by the methods and / or compositions described herein. Such an organism is preferably a mammal (e.g., a mouse, a monkey, an horse, a cow, a pig, a dog, a cat, etc.), more preferably a human (e.g., an adult human).

[0030] As used herein, a "buffer" refers to an aqueous solution that is resistant to changes in pH. Buffers may include "buffering agents," such as weak acids and their salts or weak bases and their salts, which help maintain pH stability. Examples of buffers used in pharmaceutical formulations include bicarbonate buffers, carbonate buffers, citrate buffers, histidine buffers, phosphate buffers, tartrate buffers, tris(hydroxymethyl)aminomethane (or 2-amino-2-hydroxymethyl-propane-1,3-diol [(HOCH2)3CNH2]) buffers, and combinations thereof. Some of these buffers are suitable for pharmaceutical formulations administered subcutaneously.

[0031] Tris(hydroxymethyl)aminomethane or tris(hydroxymethyl)aminomethane buffer may also be referred to as "TRIS," "Tris," "Tris buffer," "Trisamine," "THAM," "tromethamine," and other names. Furthermore, many buffers and / or buffering systems can include Tris or its pharmaceutically acceptable salts and can be used in the present teachings. For example, Tris-buffered saline ("TBS"), Tris-hydrochloride buffer ("Tris-HCl"), Tris base (pH 10.6), Tris / borate / ethylenediaminetetraacetate ("EDTA") buffer ("TBE"), and Tris / acetate / EDTA buffer ("TAE"). Tris base is often used with Tris-HCl to prepare Tris buffers at desired pHs. Furthermore, the present teachings can include Tris-related compounds, e.g., compounds derived from or structurally related to Tris, that can act as buffers.

[0032] As used herein, "isotonicity" refers to the ionic strength or concentration of ions in a solution, such as a pharmaceutical formulation. Isotonicity is often measured in molarity ("M"). As used herein, "isotonic solution," "isotonic formulation," "isotonic pharmaceutical formulation," and pharmaceutical formulations that are "isotonic" refer to a solution or formulation that has ion concentrations that are the same as or similar to the concentrations of ions found in bodily fluids.

[0033] As used herein, "physiological pH" refers to a pH of about 7.4.

[0034] As used herein, "osmolality" and "osmolality" refer to the osmotic pressure of a solution, such as a pharmaceutical formulation. Osmolality is often measured in osmolality ("Osm / L" or "OsM") or osmolality ("Osm / kg"), which may be used interchangeably herein. When measuring freezing point depression, the observed value is the osmolality of the solution. In contrast to isotonicity, osmolality takes into account non-ionized solutes in a solution, which, if present, will cause the osmolality or osmolality of a solution to be higher than the isotonicity of that solution. The osmolality of the liquid pharmaceutical formulations described herein can be measured, for example, using vapor pressure methods.

[0035] As used herein, "osmolality adjusting agent" and "osmotic agent" refer to pharmaceutically acceptable compounds that can be added to liquid pharmaceutical formulations described herein to adjust the osmolality of the liquid pharmaceutical formulations.

[0036] As used herein, "pharmaceutically acceptable" refers to a substance that is acceptable for use in pharmaceutical applications from a toxicological standpoint and does not adversely interact with the active ingredient. Thus, a pharmaceutically acceptable carrier is one that is compatible with other ingredients in the formulation and is biologically acceptable. In certain embodiments, additional active ingredients can also be incorporated into the pharmaceutical composition.

[0037] As used herein, "pharmaceutically acceptable excipient" refers to a substance that aids in the administration of an active agent to and / or the absorption of an active agent by a subject and that can be included in the compositions and formulations of the present invention without causing significant adverse toxic effects to the patient. In certain embodiments, the pharmaceutically acceptable excipients described herein can also be used to improve the stability of the liquid pharmaceutical formulations or unit liquid pharmaceutical formulations described herein. In certain embodiments, the pharmaceutically acceptable excipients described herein can also be used to improve the solubility of the loop diuretic in the liquid pharmaceutical formulations or unit liquid pharmaceutical formulations described herein. Non-limiting examples of pharmaceutically acceptable excipients include liquid vehicles such as water, NaCl, normal saline, buffers such as buffered saline, and phosphate-buffered saline, emulsion components or compounds (e.g., oil-in-water or water-in-oil emulsions), lactated Ringer's solution, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coating agents, sweeteners, flavorings, salt solutions (such as Ringer's solution), alcohols, oils, gelatin, lactose, carbohydrates such as amylose or starch, fatty acid esters, hydroxypropylmethylcellulose, polyvinylpyrrolidine, and coloring agents. Such preparations can be sterilized and, if desired, can be mixed with auxiliary excipients that do not deleteriously react with the compounds of the invention, such as lubricants, preservatives, stabilizers, solubilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring and / or flavoring substances, etc. For examples of excipients and carriers, see Martin, Remington's Pharmaceutical Sciences, 15th Ed., Mack Publ. Co., Easton, PA (1975).

[0038] As used herein, the term "pharmaceutically acceptable carrier" refers to standard pharmaceutical carriers, such as buffers such as phosphate-buffered saline or tromethamine-buffered aqueous solutions, water (e.g., water for injection (WFI)), emulsions (e.g., oil-in-water or water-in-oil emulsions), and any of various types of wetting agents. The composition may also include stabilizers and preservatives. For examples of carriers, stabilizers, and adjuvants, see Martin, Remington's Pharmaceutical Sciences, 15th Ed., Mack Publ. Co., Easton, PA

[1975] .

[0039] As used herein, the term "pharmaceutically acceptable salt" refers to any pharmaceutically acceptable salt (e.g., acid or base) of a compound of the present invention (e.g., a loop diuretic described herein) that, upon administration to a subject, is capable of providing a compound of the present invention or an active metabolite or residue thereof. As known to those skilled in the art, "salts" of the compounds of the present invention can be derived from inorganic or organic acids and bases. Examples of acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, ethanesulfonic acid, formic acid, benzoic acid, malonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, and the like. Other acids, such as oxalic acid, while not themselves pharmaceutically acceptable, may be used in the preparation of salts useful as intermediates in obtaining the compounds of the present invention and their pharmaceutically acceptable acid addition salts.

[0040] Examples of bases include alkali metal (e.g., sodium) hydroxides, alkaline earth metal (e.g., magnesium) hydroxides, ammonia, and bases of formula NW4 + (Wherein W is C 1-4 Examples of suitable compounds include, but are not limited to, compounds of the formula:

[0041] Examples of salts include, but are not limited to, acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, undecanoate, etc. Other examples of salts include those containing a suitable cation, e.g., Na + , NH4 + , and NW4 + (Wherein W is C 1-4 Examples of the anion of the compound of the present invention include an anion having a substituent such as an alkyl group.

[0042] As used herein, unless otherwise stated, all weights stated herein should be understood to correspond to the weight of the compound in its free acid / free base form (e.g., furosemide, torsemide, bumetanide).

[0043] As used herein, the term "effective amount" refers to an amount of a composition (e.g., a liquid pharmaceutical formulation or a compound disclosed herein) sufficient to produce a beneficial or desired result. An effective amount can be administered in one or more administrations, applications, or dosages, and is not intended to be limited to a particular formulation or route of administration.

[0044] As used herein, the terms "treat," "treating," and "treatment" include any effect that results in improvement of a condition, disease, disorder, etc., or the amelioration of a symptom thereof, e.g., alleviation, reduction, modulation, remission, or elimination.

[0045] As used herein, the phrase "therapeutically effective amount" refers to an amount of a composition (e.g., a liquid pharmaceutical formulation or a compound disclosed herein) effective to produce some desired therapeutic effect in a subject.

[0046] As used herein, the term "congestion" (in heart failure) refers to the presence of signs and symptoms of extracellular fluid accumulation resulting in elevated cardiac filling pressures that cause reduced cardiac output, which is further exacerbated by neurohormonal activation, causing increased renal sodium and water binding capacity, resulting in plasma volume expansion.

[0047] As used herein, "fluid overload," "volume overload," and "hypervolemia" can refer to a medical condition in which there is too much fluid in the blood. Excess fluid, primarily salt and water, can accumulate throughout the body and lead to weight gain.

[0048] Throughout the description, when compositions and kits are described as having, including, or comprising particular components, or when processes and methods are described as having, including, or comprising particular steps, it is additionally contemplated that there are compositions and kits of the invention that consist essentially of or consist of the recited components, and that there are processes and methods of the invention that consist essentially of or consist of the recited processing steps.

[0049] As a general matter, compositions in which percentages are specified are by weight unless otherwise specified. Furthermore, if a definition is not provided for a variable, the previous definition for that variable takes precedence.

[0050] Liquid pharmaceutical formulation of loop diuretic As described herein, in one aspect, the invention provides a liquid pharmaceutical formulation of a loop diuretic, eg, a loop diuretic, and a pharmaceutically acceptable excipient.

[0051] In various embodiments, the liquid pharmaceutical formulation generally comprises: (i) a therapeutically effective amount of a loop diuretic, or a pharmaceutically acceptable salt thereof, and (ii) a pharmaceutically acceptable buffer.

[0052] Loop diuretics In certain embodiments, the concentration of the loop diuretic, or a pharmaceutically acceptable salt thereof, in the liquid pharmaceutical formulations described herein is from about 0.025 mg / mL to about 250 mg / mL, from about 0.1 mg / mL to about 250 mg / mL, from about 1 mg / mL to about 250 mg / mL, from about 5 mg / mL to about 250 mg / mL, from about 10 mg / mL to about 250 mg / mL, from about 20 mg / mL to about 250 mg / mL, from about 30 mg / mL to about 250 mg / mL, from about 40 mg / mL to about 250 mg / mL, from about 50 mg / mL to about 250 mg / mL, or from about 60 mg / mL to about 250 mg / mL. L, about 70 mg / mL to about 250 mg / mL, about 80 mg / mL to about 250 mg / mL, about 90 mg / mL to about 250 mg / mL, about 100 mg / mL to about 250 mg / mL, about 120 mg / mL to about 250 mg / mL, about 140 mg / mL to about 250 mg / mL, about 160 m g / mL~about 250mg / mL, about 180mg / mL~about 250mg / mL, about 200mg / mL~about 250mg / mL, about 225mg / mL~about 250mg / mL, about 0.025mg / mL~about 225mg / mL, about 0.025mg / mL~about 200mg / mL, about 0.02 5mg / mL to about 180mg / mL, about 0.025mg / mL to about 160mg / mL, about 0.025mg / mL to about 140mg / mL, about 0.025mg / mL to about 120mg / mL, about 0.025mg / mL to about 100mg / mL, about 0.025mg / mL to about 90mg / m L, about 0.025 mg / mL to about 80 mg / mL, about 0.025 mg / mL to about 70 mg / mL, about 0.025 mg / mL to about 60 mg / mL, about 0.025 mg / mL to about 50 mg / mL, about 0.025 mg / mL to about 40 mg / mL, about 0.025 mg / mL to about 30 mg / mL, about 0.025mg / mL to about 20mg / mL, about 0.025mg / mL to about 10mg / mL, about 0.025mg / mL to about 5mg / mL, about 0.025mg / mL to about 1mg / mL, about 0.025mg / mL to about 0.1mg / mL, about 0.1mg / mL to about 225mg / mL, about 0.1 mg / mL to about 200 mg / mL, about 0.1 mg / mL to about 180 mg / mL, about 0.1 mg / mL to about 160 mg / mL, about 0.1 mg / mL to about 140 mg / mL, about 0.1 mg / mL to about 120 mg / mL, about 0.1 mg / mL to about 100 mg / mL,about 0.1 mg / mL to about 90 mg / mL, about 0.1 mg / mL to about 80 mg / mL, about 0.1 mg / mL to about 70 mg / mL, about 0.1 mg / mL to about 60 mg / mL, about 0.1 mg / mL to about 50 mg / mL, about 0.1 mg / mL to about 40 mg / mL, about 0.1 mg / mL to about 30 mg / mL, about 0.1 mg / mL to about 20 mg / mL, about 0.1 mg / mL to about 10 mg / mL, about 0.1 mg / mL to about 5 mg / mL, about 0.1 mg / mL to about 1 mg / mL, about 1 mg / mL to about 225 mg / mL, about 1 mg / mL to about 200 mg / mL, about 1 mg / mL g / mL to about 180 mg / mL, about 1 mg / mL to about 160 mg / mL, about 1 mg / mL to about 140 mg / mL, about 1 mg / mL to about 120 mg / mL, about 1 mg / mL to about 100 mg / mL, about 1 mg / mL to about 90 mg / mL, about 1 mg / mL to about 80 mg / mL, about 1 mg / mL to about 70 mg / mL, about 1 mg / mL to about 60 mg / mL, about 1 mg / mL to about 50 mg / mL, about 1 mg / mL to about 40 mg / mL, about 1 mg / mL to about 30 mg / mL, about 1 mg / mL to about 20 mg / mL, about 1 mg / mL to about 10 mg / mL, about 1 mg / mL to about 5 mg / mL, about 5 mg / mL to about 225 mg / mL, about 5 mg / mL to about 200 mg / mL, about 5 mg / mL to about 180 mg / mL, about 5 mg / mL to about 160 mg / mL, about 5 mg / mL to about 140 mg / mL, about 5 mg / mL to about 120 mg / mL, about 5 mg / mL to about 100 mg / mL, about 5 mg / mL to about 90 mg / mL, about 5 mg / mL to about 80 mg / mL, about 5 mg / mL to about 70 mg / mL, about 5 mg / mL to about 60 mg / mL, about 5 mg / mL to about 50 mg / mL, about 5 mg / mL to about 40 mg / mL, about 5 mg / mL to about 30 mg / mL, about 5 mg / mL to about 20 mg / mL, about 5 mg / mL to about 10 mg / mL, about 10 mg / mL to about 225 mg / mL, about 10 mg / mL to about 200 mg / mL, about 10 mg / mL to about 180 mg / mL, about 10 mg / mL to about 160 mg / mL, about 10 mg / mL to about 140 mg / mL, about 10 mg / mL to about 120 mg / mL, about 10 mg / mL to about 100 mg / mL, about 10 mg / mL to about 90 mg / mL, about 10 mg / mL to about 80 mg / mL, about 10 mg / mL to about 70 mg / mL, about 10 mg / mL to about 60 mg / mL,about 10 mg / mL to about 50 mg / mL, about 10 mg / mL to about 40 mg / mL, about 10 mg / mL to about 30 mg / mL, about 10 mg / mL to about 20 mg / mL, about 20 mg / mL to about 225 mg / mL, about 20 mg / mL to about 200 mg / mL, about 20 mg / mL to about 180 mg / mL, about 20 mg / mL to about 160 mg / mL, about 20 mg / mL to about 140 mg / mL, about 20 mg / mL to about 120 mg / mL, about 20 mg / mL to about 100 mg / mL, about 20 mg / mL to about 90 mg / mL, about 20 mg / mL to about 80 mg / mL, about 20 mg / mL to about 70 mg / mL, about 20 mg / mL to about 60 mg / mL, about 20 mg / mL to about 50 mg / mL, about 20 mg / mL to about 40 mg / mL, about 20 mg / mL to about 30 mg / mL, about 30 mg / mL to about 225 mg / mL, about 30 mg / mL to about 200 mg / mL, about 30 mg / mL to about 180 mg / mL, about 30 mg / mL to about 160 mg / mL, about 30 mg / mL to about 140 mg / mL, about 30 mg / mL to about 120 mg / mL, about 30 mg / mL to about 100 mg / mL, about 30 mg / mL to about 90 mg / mL, about 30 mg / mL to about 80 mg / mL, about 30 mg / mL to about 70 mg / mL, about 30 mg / mL to about 60 mg / mL, about 30 mg / mL to about 50 mg / mL, about 30 mg / mL to about 40 mg / mL, about 40 mg / mL to about 225 mg / mL, about 40 mg / mL to about 200 mg / mL, about 40 mg / mL to about 180 mg / mL, about 40 mg / mL to about 160 mg / mL, about 40 mg / mL to about 140 mg / mL, about 40 mg / mL to about 120 mg / mL, about 40 mg / mL to about 100 mg / mL, about 40 mg / mL to about 90 mg / mL, about 40 mg / mL to about 80 mg / mL, about 40 mg / mL to about 70 mg / mL, about 40 mg / mL to about 60 mg / mL, about 40 mg / mL to about 50 mg / mL, about 50 mg / mL to about 225 mg / mL, about 50 mg / mL to about 200 mg / mL, about 50 mg / mL to about 180 mg / mL, about 50 mg / mL to about 160 mg / mL, about 50 mg / mL to about 140 mg / mL, about 50 mg / mL to about 120 mg / mL, about 50 mg / mL to about 100 mg / mL, about 50 mg / mL to about 90 mg / mL, about 50 mg / mL to about 80 mg / mL, about 50 mg / mL to about 70 mg / mL, about 50 mg / mL to about 60 mg / mL,about 60 mg / mL to about 225 mg / mL, about 60 mg / mL to about 200 mg / mL, about 60 mg / mL to about 180 mg / mL, about 60 mg / mL to about 160 mg / mL, about 60 mg / mL to about 140 mg / mL, about 60 mg / mL to about 120 mg / mL, about 60 mg / mL to about 100 mg / mL, about 60 mg / mL to about 90 mg / mL, about 60 mg / mL to about 80 mg / mL, about 60 mg / mL to about 70 mg / mL, about 70 mg / mL to about 225 mg / mL, about 70 mg / mL to about 200 mg / mL, about 70 mg / mL to about 180 mg / mL, about 70 mg / mL to About 160 mg / mL, about 70 mg / mL to about 140 mg / mL, about 70 mg / mL to about 120 mg / mL, about 70 mg / mL to about 100 mg / mL, about 70 mg / mL to about 90 mg / mL, about 70 mg / mL to about 80 mg / mL, about 70 mg / mL to about 225 mg / mL, about 80 mg / mL to about 200 mg / mL, about 80 mg / mL to about 180 mg / mL, about 80 mg / mL to about 160 mg / mL, about 80 mg / mL to about 140 mg / mL, about 80 mg / mL to about 120 mg / mL, about 80 mg / mL to about 100 mg / mL, about 80 mg / mL g / mL to about 90 mg / mL, about 70 mg / mL to about 225 mg / mL, about 90 mg / mL to about 200 mg / mL, about 90 mg / mL to about 180 mg / mL, about 90 mg / mL to about 160 mg / mL, about 90 mg / mL to about 140 mg / mL, about 90 mg / mL to about 120 mg / mL, about 90 mg / mL to about 100 mg / mL, about 100 mg / mL to about 225 mg / mL, about 100 mg / mL to about 200 mg / mL, about 100 mg / mL to about 180 mg / mL, about 100 mg / mL to about 160 mg / mL, about 100 mg / mL to about 140 mg / mL, about 100 mg / mL to about 120 mg / mL, about 120 mg / mL to about 225 mg / mL, about 120 mg / mL to about 200 mg / mL, about 120 mg / mL to about 180 mg / mL, about 120 mg / mL to about 160 mg / mL, about 120 mg / mL to about 140 mg / mL, about 140 mg / mL to about 225 mg / mL, about 140 mg / mL to about 200 mg / mL, about 140 mg / mL to about 180 mg / mL, about 140 mg / mL to about 160 mg / mL, about 160 mg / mL to about 225 mg / mL, about 160 mg / mL to about 200 mg / mL, about 160 mg / mL to about 180 mg / mL,The concentration of the loop diuretic, or a pharmaceutically acceptable salt thereof, in the liquid pharmaceutical formulations described herein can be about 0.025 mg / mL to about 250 mg / mL.

[0053] In certain embodiments, the concentration of the loop diuretic, or a pharmaceutically acceptable salt thereof, in the liquid pharmaceutical formulations described herein is greater than about 0.025 mg / mL, greater than about 0.1 mg / mL, greater than about 1 mg / mL, greater than about 5 mg / mL, greater than about 10 mg / mL, greater than about 20 mg / mL, greater than about 30 mg / mL, greater than about 40 mg / mL, greater than about 50 mg / mL, greater than about 60 mg / mL, greater than about 70 mg / mL, greater than about 80 mg / mL, greater than about 90 mg / mL The concentration can be greater than about 100 mg / mL, greater than about 110 mg / mL, greater than about 120 mg / mL, greater than about 130 mg / mL, greater than about 140 mg / mL, greater than about 150 mg / mL, greater than about 160 mg / mL, greater than about 170 mg / mL, greater than about 180 mg / mL, greater than about 190 mg / mL, greater than about 200 mg / mL, greater than about 210 mg / mL, greater than about 220 mg / mL, greater than about 230 mg / mL, greater than about 240 mg / mL, or greater than about 250 mg / mL.

[0054] In certain embodiments, the concentration of the loop diuretic, or a pharmaceutically acceptable salt thereof, in the liquid pharmaceutical formulations described herein is about 0.025 mg / mL, about 0.05 mg / mL, about 0.075 mg / mL, about 0.1 mg / mL, about 0.2 mg / mL, about 0.3 mg / mL, about 0.4 mg / mL, about 0.5 mg / mL, about 0.6 mg / mL, about 0.7 mg / mL, about 0.8 mg / mL, about 0.9 mg / mL, about 1 mg / mL, approximately 2 mg / mL, approximately 3 mg / mL, approximately 4 mg / mL, approximately 5 mg / mL, approximately 6 mg / mL, approximately 7 mg / mL, approximately 8 mg / mL, approximately 9 mg / mL, approximately 10 mg / mL, approximately 11 mg / mL, approximately 12 m g / mL, approximately 13 mg / mL, approximately 14 mg / mL, approximately 15 mg / mL, approximately 16 mg / mL, approximately 17 mg / mL, approximately 18 mg / mL, approximately 19 mg / mL, approximately 20 mg / mL, approximately 22 mg / mL, approximately 24 mg / mL mL, approximately 26 mg / mL, approximately 28 mg / mL, approximately 30 mg / mL, approximately 32 mg / mL, approximately 34 mg / mL, approximately 36 mg / mL, approximately 38 mg / mL, approximately 40 mg / mL, approximately 42 mg / mL, approximately 44 mg / mL , about 46 mg / mL, about 48 mg / mL, about 50 mg / mL, about 55 mg / mL, about 60 mg / mL, about 65 mg / mL, about 70 mg / mL, about 75 mg / mL, about 80 mg / mL, about 85 mg / mL, about It can be 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 110 mg / mL, about 120 mg / mL, about 130 mg / mL, about 140 mg / mL, about 150 mg / mL, about 160 mg / mL, about 170 mg / mL, about 180 mg / mL, about 190 mg / mL, about 200 mg / mL, about 210 mg / mL, about 220 mg / mL, about 230 mg / mL, about 240 mg / mL, or about 250 mg / mL.

[0055] In certain embodiments, the loop diuretic is selected from the group consisting of furosemide, bumetanide, ethacrynic acid, torsemide, or a pharmaceutically acceptable salt thereof. In certain embodiments, the loop diuretic is furosemide or a pharmaceutically acceptable salt thereof. In certain embodiments, the loop diuretic is bumetanide or a pharmaceutically acceptable salt thereof. In certain embodiments, the loop diuretic is ethacrynic acid or a pharmaceutically acceptable salt thereof. In certain embodiments, the loop diuretic is torsemide or a pharmaceutically acceptable salt thereof.

[0056] In certain embodiments, the concentration of furosemide in the liquid pharmaceutical formulations described herein is from about 1 mg / mL to about 250 mg / mL, from about 5 mg / mL to about 250 mg / mL, from about 10 mg / mL to about 250 mg / mL, from about 20 mg / mL to about 250 mg / mL, from about 30 mg / mL to about 250 mg / mL, from about 40 mg / mL to about 250 mg / mL, from about 50 mg / mL to about 250 mg / mL, from about 60 mg / mL to about 250 mg / mL, from about 70 mg / mL to about 250 mg / mL, from about 80 mg / mL to about 250 mg / mL, from about 90 mg / mL to about 250 mg / mL, or from about 1 00mg / mL~about 250mg / mL, about 120mg / mL~about 250mg / mL, about 140mg / mL~about 250mg / mL, about 160mg / mL~about 250mg / mL, about 180mg / mL~about 250mg / mL, about 200mg / mL~about 250mg / mL, about 225mg / mL mL~about 250mg / mL, about 1mg / mL~about 225mg / mL, about 1mg / mL~about 200mg / mL, about 1mg / mL~about 180mg / mL, about 1mg / mL~about 160mg / mL, about 1mg / mL~about 140mg / mL, about 1mg / mL~about 120mg / mL, about 1mg / mL~about 100mg / mL, about 1mg / mL~about 90mg / mL, about 1mg / mL~about 80mg / mL, about 1mg / mL~about 70mg / mL, about 1mg / mL~about 60mg / mL, about 1mg / mL~about 50mg / mL, about 1mg / mL~about 40mg / mL, about 1mg / mL~about 30mg / mL, about 1mg / mL to about 20mg / mL, about 1mg / mL to about 10mg / mL, about 1mg / mL to about 5mg / mL, about 5mg / mL to about 225mg / mL, about 5mg / mL to about 200mg / mL, about 5mg / mL to about 180mg / mL, about 5mg / mL to about 160m g / mL, approximately 5 mg / mL to approximately 140 mg / mL, approximately 5 mg / mL to approximately 120 mg / mL, approximately 5 mg / mL to approximately 100 mg / mL, approximately 5 mg / mL to approximately 90 mg / mL, approximately 5 mg / mL to approximately 80 mg / mL, approximately 5 mg / mL to approximately 70 mg / mL, approximately 5 mg / mL to approximately 60 mg / m L, about 5 mg / mL to about 50 mg / mL, about 5 mg / mL to about 40 mg / mL, about 5 mg / mL to about 30 mg / mL, about 5 mg / mL to about 20 mg / mL, about 5 mg / mL to about 10 mg / mL, about 10 mg / mL to about 225 mg / mL, about 10 mg / mL to about 200 mg / mL,about 10 mg / mL to about 180 mg / mL, about 10 mg / mL to about 160 mg / mL, about 10 mg / mL to about 140 mg / mL, about 10 mg / mL to about 120 mg / mL, about 10 mg / mL to about 100 mg / mL, about 10 mg / mL to about 90 mg / mL, about 10 mg / mL to about 80 mg / mL, about 10 mg / mL to about 70 mg / mL, about 10 mg / mL to about 60 mg / mL, about 10 mg / mL to about 50 mg / mL, about 10 mg / mL to about 40 mg / mL, about 10 mg / mL to about 30 mg / mL, about 10 mg / mL to about 20 mg / mL, about 20 mg / mL to about 2 25 mg / mL, about 20 mg / mL to about 200 mg / mL, about 20 mg / mL to about 180 mg / mL, about 20 mg / mL to about 160 mg / mL, about 20 mg / mL to about 140 mg / mL, about 20 mg / mL to about 120 mg / mL, about 20 mg / mL to about 100 mg / mL, about 20 mg / mL to about 90 mg / mL, about 20 mg / mL to about 80 mg / mL, about 20 mg / mL to about 70 mg / mL, about 20 mg / mL to about 60 mg / mL, about 20 mg / mL to about 50 mg / mL, about 20 mg / mL to about 40 mg / mL, about 20 mg / mL to about 30 mg / mL, about 3 0 mg / mL to about 225 mg / mL, about 30 mg / mL to about 200 mg / mL, about 30 mg / mL to about 180 mg / mL, about 30 mg / mL to about 160 mg / mL, about 30 mg / mL to about 140 mg / mL, about 30 mg / mL to about 120 mg / mL, about 30 mg / mL to about 100 mg / mL, about 30 mg / mL to about 90 mg / mL, about 30 mg / mL to about 80 mg / mL, about 30 mg / mL to about 70 mg / mL, about 30 mg / mL to about 60 mg / mL, about 30 mg / mL to about 50 mg / mL, about 30 mg / mL to about 40 mg / mL, about 40 mg / mL to about 2 25 mg / mL, about 40 mg / mL to about 200 mg / mL, about 40 mg / mL to about 180 mg / mL, about 40 mg / mL to about 160 mg / mL, about 40 mg / mL to about 140 mg / mL, about 40 mg / mL to about 120 mg / mL, about 40 mg / mL to about 100 mg / mL, about 40 mg / mL to about 90 mg / mL, about 40 mg / mL to about 80 mg / mL, about 40 mg / mL to about 70 mg / mL, about 40 mg / mL to about 60 mg / mL, about 40 mg / mL to about 50 mg / mL, about 50 mg / mL to about 225 mg / mL, about 50 mg / mL to about 200 mg / mL,about 50 mg / mL to about 180 mg / mL, about 50 mg / mL to about 160 mg / mL, about 50 mg / mL to about 140 mg / mL, about 50 mg / mL to about 120 mg / mL, about 50 mg / mL to about 100 mg / mL, about 50 mg / mL to about 90 mg / mL, about 50 mg / mL to about 80 mg / mL, about 50 mg / mL to about 70 mg / mL, about 50 mg / mL to about 60 mg / mL, about 60 mg / mL to about 225 mg / mL, about 60 mg / mL to about 200 mg / mL, about 60 mg / mL to about 180 mg / mL, about 60 mg / mL to about 160 mg / mL, about 60 mg / mL L to about 140 mg / mL, about 60 mg / mL to about 120 mg / mL, about 60 mg / mL to about 100 mg / mL, about 60 mg / mL to about 90 mg / mL, about 60 mg / mL to about 80 mg / mL, about 60 mg / mL to about 70 mg / mL, about 70 mg / mL to about 225 mg / mL, about 70 mg / mL to about 200 mg / mL, about 70 mg / mL to about 180 mg / mL, about 70 mg / mL to about 160 mg / mL, about 70 mg / mL to about 140 mg / mL, about 70 mg / mL to about 120 mg / mL, about 70 mg / mL to about 100 mg / mL, about 70 mg / mL to about 90 mg / mL g / mL, about 70 mg / mL to about 80 mg / mL, about 70 mg / mL to about 225 mg / mL, about 80 mg / mL to about 200 mg / mL, about 80 mg / mL to about 180 mg / mL, about 80 mg / mL to about 160 mg / mL, about 80 mg / mL to about 140 mg / mL, about 80 mg / mL to about 120 mg / mL, about 80 mg / mL to about 100 mg / mL, about 80 mg / mL to about 90 mg / mL, about 70 mg / mL to about 225 mg / mL, about 90 mg / mL to about 200 mg / mL, about 90 mg / mL to about 180 mg / mL, about 90 mg / mL to about 160 mg / mL, about 90 mg / mL to about 140 mg / mL, about 90 mg / mL to about 120 mg / mL, about 90 mg / mL to about 100 mg / mL, about 100 mg / mL to about 225 mg / mL, about 100 mg / mL to about 200 mg / mL, about 100 mg / mL to about 180 mg / mL, about 100 mg / mL to about 160 mg / mL, about 100 mg / mL to about 140 mg / mL, about 100 mg / mL to about 120 mg / mL, about 120 mg / mL to about 225 mg / mL, about 120 mg / mL to about 200 mg / mL, about 120 mg / mL to about 180 mg / mL,The concentration of furosemide in the liquid pharmaceutical formulations described herein can be about 1 mg / mL to about 250 mg / mL.

[0057] In certain embodiments, the concentration of furosemide in the liquid pharmaceutical formulations described herein is greater than about 1 mg / mL, greater than about 5 mg / mL, greater than about 10 mg / mL, greater than about 20 mg / mL, greater than about 30 mg / mL, greater than about 40 mg / mL, greater than about 50 mg / mL, greater than about 60 mg / mL, greater than about 70 mg / mL, greater than about 80 mg / mL, greater than about 90 mg / mL, greater than about 100 mg / mL, greater than about 110 mg / mL, greater than about 120 mg / mL, greater than about 140 mg / mL, greater than about 160 mg / mL, greater than about 180 mg / mL, greater than about 190 mg / mL, greater than about 210 mg / mL, greater than about 220 mg / mL, greater than about 240 mg / mL, greater than about 250 mg / mL, greater than about 260 mg / mL, greater than about 270 mg / mL, greater than about 280 mg / mL, greater than about 290 mg / mL, greater than about 300 mg / mL, greater than about 310 mg / mL, greater than about 320 mg / mL, greater than about 330 mg / mL, greater than about 340 mg / mL, greater than about 350 mg / mL, greater than about 360 mg / mL, greater than about 370 mg / mL, greater than about 380 mg / mL, greater than about 390 mg / mL, greater than about 400 mg / mL, greater than about 410 mg / mL, greater than about 420 mg / mL, greater than about 450 mg / mL, greater than about 460 mg / mL, greater than about 470 mg / mL, greater than about 480 mg / mL, greater than about 490 mg / mL, greater than about 500 mg / mL, greater than about 510 mg mL, greater than about 120 mg / mL, greater than about 130 mg / mL, greater than about 140 mg / mL, greater than about 150 mg / mL, greater than about 160 mg / mL, greater than about 170 mg / mL, greater than about 180 mg / mL, greater than about 190 mg / mL, greater than about 200 mg / mL, greater than about 210 mg / mL, greater than about 220 mg / mL, greater than about 230 mg / mL, greater than about 240 mg / mL, or greater than about 250 mg / mL.

[0058] In certain embodiments, the concentration of furosemide in the liquid pharmaceutical formulations described herein is about 1 mg / mL, about 2 mg / mL, about 3 mg / mL, about 4 mg / mL, about 5 mg / mL, about 6 mg / mL, about 7 mg / mL, about 8 mg / mL, about 9 mg / mL, about 10 mg / mL, about 11 mg / mL, about 12 mg / mL, about 13 mg / mL, about 14 mg / mL, about 15 mg / mL, about 16 mg / mL, about 17 mg / mL, about 18 mg / mL, about 19 mg / mL, about 20 mg / mL, about 22 mg / mL, about 24 mg / mL, about 26 mg / mL, about 28 mg / mL, about 30 mg / mL, about 32 mg / mL, about 34 mg / mL, about 36 mg / mL, about 38 mg / mL, about 40 mg / mL, about 42 mg / mL, about 44 mg / mL, about 45 mg / mL, about 46 mg / mL, about 47 mg / mL, about 48 mg / mL, about 49 mg / mL, about 50 mg / mL, about 51 mg / mL, about 52 mg / mL, about 53 mg / mL, about 54 mg / mL, about 55 mg / mL, about 56 mg / mL, about 57 mg / mL, about 58 mg / mL, about 59 mg / mL, about 60 mg / mL, about 61 mg / mL, about 62 mg / mL, about 63 mg / mL, about 64 mg / mL, about 65 mg / mL, about 66 mg / mL, about 67 mg / mL, about 68 mg / mL, about 69 mg / mL, about 70 mg / mL, about 71 mg / mL, about 72 mg / mL, about 73 mg / mL, about 74 mg / mL, about 7 42 mg / mL, about 44 mg / mL, about 46 mg / mL, about 48 mg / mL, about 50 mg / mL, about 55 mg / mL, about 60 mg / mL, about 65 mg / mL, about 70 mg / mL, about 75 mg / mL, about 80 mg / mL, about 85 mg / mL, about 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 110 mg / mL, about 120 mg / mL, about 130 mg / mL, about 140 mg / mL, about 150 mg / mL, about 160 mg / mL, about 170 mg / mL, about 180 mg / mL, about 190 mg / mL, about 200 mg / mL, about 210 mg / mL, about 220 mg / mL, about 230 mg / mL, about 240 mg / mL, or about 250 mg / mL. In certain embodiments, the concentration of furosemide in the liquid pharmaceutical formulations described herein may be about 80 mg / mL.

[0059] In certain embodiments, the concentration of bumetanide in the liquid pharmaceutical formulations described herein is from about 0.025 mg / mL to about 65 mg / mL, from about 0.1 mg / mL to about 65 mg / mL, from about 0.5 mg / mL to about 65 mg / mL, from about 1 mg / mL to about 65 mg / mL, from about 5 mg / mL to about 65 mg / mL, from about 10 mg / mL to about 65 mg / mL, from about 20 mg / mL to about 65 mg / mL, from about 30 mg / mL to about 65 mg / mL, or from about 40mg / mL to about 65mg / mL, about 50mg / mL to about 65mg / mL, about 60mg / mL to about 65mg / mL, about 0.025mg / mL to about 60mg / mL, about 0.025mg / mL to about 50mg / mL , about 0.025 mg / mL to about 40 mg / mL, about 0.025 mg / mL to about 30 mg / mL, about 0.025 mg / mL to about 20 mg / mL, about 0.025 mg / mL to about 10 mg / mL, about 0.025 mg / m L ~ approx. 5 mg / mL, approx. 0.025 mg / mL ~ approx. 1 mg / mL, approx. 0.025 mg / mL ~ approx. 0.5 mg / mL, approx. 0.025 mg / mL ~ approx. 0.1 mg / mL, approx. 0.1 mg / mL ~ approx. 60 mg / mL, approx. 0.1mg / mL to approx. 50mg / mL, approx. 0.1mg / mL to approx. 40mg / mL, approx. 0.1mg / mL to approx. 30mg / mL, approx. 0.1mg / mL to approx. 20mg / mL, approx. 0.1mg / mL to approx. 10mg / mL, approx. 0.1mg / mL to approx. 5mg / mL, approx. 0.1mg / mL to approx. 1mg / mL, approx. 0.5mg / mL to approx. 60mg / mL, approx. 0.5mg / mL to approx. 50mg / mL, approx. 0.5mg / mL to approx. 40mg / mL, approx. 0 .5mg / mL to about 30mg / mL, about 0.5mg / mL to about 20mg / mL, about 0.5mg / mL to about 10mg / mL, about 0.5mg / mL to about 10mg / mL, about 0.5mg / mL to about 5mg / mL, about 0.5mg / mL to about 1mg / mL, about 1mg / mL to about 60mg / mL, about 1mg / mL to about 50mg / mL, about 1mg / mL to about 40mg / mL, about 1mg / mL to about 30mg / mL, about 1mg / mL to about 20mg / mL, about 1mg / mL to about 10mg / mL, about 1mg / mL to about 5m g / mL, about 5 mg / mL to about 60 mg / mL, about 5 mg / mL to about 50 mg / mL, about 5 mg / mL to about 40 mg / mL, about 5 mg / mL to about 30 mg / mL, about 5 mg / mL to about 20 mg / mL, about 5 mg / mL to about 10 mg / mL, about 10 mg / mL to about 60 mg / mL, about 10 The concentration of bumetanide in the liquid pharmaceutical formulations described herein can be from about 0.025 mg / mL to about 65 mg / mL, from about 10 mg / mL to about 40 mg / mL, from about 10 mg / mL to about 30 mg / mL, from about 10 mg / mL to about 20 mg / mL, from about 20 mg / mL to about 60 mg / mL, from about 20 mg / mL to about 50 mg / mL, from about 20 mg / mL to about 40 mg / mL, from about 20 mg / mL to about 30 mg / mL, from about 30 mg / mL to about 60 mg / mL, from about 30 mg / mL to about 50 mg / mL, from about 30 mg / mL to about 40 mg / mL, from about 40 mg / mL to about 60 mg / mL, from about 40 mg / mL to about 50 mg / mL, or from about 50 mg / mL to about 60 mg / mL. In certain embodiments, the concentration of bumetanide in the liquid pharmaceutical formulations described herein can be from about 0.025 mg / mL to about 65 mg / mL.

[0060] In certain embodiments, the concentration of bumetanide in the liquid pharmaceutical formulations described herein can be greater than about 0.025 mg / mL, greater than about 1 mg / mL, greater than about 5 mg / mL, greater than about 10 mg / mL, greater than about 20 mg / mL, greater than about 30 mg / mL, greater than about 40 mg / mL, greater than about 50 mg / mL, or greater than about 60 mg / mL.

[0061] In certain embodiments, the concentration of bumetanide in the liquid pharmaceutical formulations described herein is about 0.025 mg / mL, about 0.05 mg / mL, about 0.075 mg / mL, about 0.1 mg / mL, about 0.25 mg / mL, about 0.5 mg / mL, about 0.75 mg / mL, about 1 mg / mL, about 2 mg / mL, about 3 mg / mL, about 4 mg / mL, about 5 mg / mL, about 6 mg / mL, about 7 mg / mL, about 8 mg / mL, about 9 mg / mL, about 10 mg / mL, about 11 mg / mL, about 12 mg / mL, about 13 mg / mL, about 14 mg / mL, about 15 mg / mL, about 16 mg / mL, about 17 mg / mL, about 18 mg / mL, about 19 mg / mL, about 20 mg / mL, about 21 mg / mL, about 22 mg / mL, about 23 mg / mL, about 24 mg / mL, about 25 mg / mL, about 26 mg / mL, about 27 mg / mL, about 28 mg / mL, about 29 mg / mL, about 30 mg / mL, about 31 mg / mL, about 32 mg / mL, about 33 mg / mL, about 34 mg / mL, about 35 mg / mL, about 36 mg / mL, about 37 mg / mL, about 38 mg / mL, about 39 mg / mL, about 40 mg / mL, about 41 mg / mL, about 42 mg / mL, about 43 mg / mL, about 44 mg / mL, about 45 mg / mL, about 46 mg / mL, about 47 mg / mL, about 48 mg / mL, about 49 mg / mL, about 50 mg / mL, about 51 mg / mL, about 52 mg / mL, about 53 mg / mL, about 54 mg / The concentration can be about 15 mg / mL, about 16 mg / mL, about 17 mg / mL, about 18 mg / mL, about 19 mg / mL, about 20 mg / mL, about 22 mg / mL, about 24 mg / mL, about 26 mg / mL, about 28 mg / mL, about 30 mg / mL, about 32 mg / mL, about 34 mg / mL, about 36 mg / mL, about 38 mg / mL, about 40 mg / mL, about 42 mg / mL, about 44 mg / mL, about 46 mg / mL, about 48 mg / mL, about 50 mg / mL, about 55 mg / mL, about 60 mg / mL, or about 65 mg / mL.

[0062] In certain embodiments, the concentration of torsemide in the liquid pharmaceutical formulations described herein is from about 0.5 mg / mL to about 125 mg / mL, from about 1 mg / mL to about 125 mg / mL, from about 5 mg / mL to about 125 mg / mL, from about 10 mg / mL to about 125 mg / mL, from about 20 mg / mL to about 125 mg / mL, from about 30 mg / mL to about 125 mg / mL, from about 40 mg / mL to about 125 mg / mL, from about 50 mg / mL to about 125 mg / mL, from about 75mg / mL to about 125mg / mL, about 100mg / mL to about 125mg / mL, about 0.5mg / mL to about 100mg / mL, about 0.5mg / mL to about 75mg / mL, about 0.5mg / mL to about 50mg / mL, Approx. 0.5 mg / mL to approx. 40 mg / mL, approx. 0.5 mg / mL to approx. 30 mg / mL, approx. 0.5 mg / mL to approx. 20 mg / mL, approx. 0.5 mg / mL to approx. 10 mg / mL, approx. 0.5 mg / mL to approx. 5 mg / mL, approx.5mg / mL to about 1mg / mL, about 1mg / mL to about 100mg / mL, about 1mg / mL to about 75mg / mL, about 1mg / mL to about 50mg / mL, about 1mg / mL to about 40mg / m L, about 1 mg / mL to about 30 mg / mL, about 1 mg / mL to about 20 mg / mL, about 1 mg / mL to about 10 mg / mL, about 1 mg / mL to about 5 mg / mL, about 5 mg / mL to about 100 mg / mL, about 5 mg / mL to about 75 mg / mL, about 5 mg / mL to about 50 mg / mL, about 5 mg / mL to about 40 mg / mL, about 5 mg / mL to about 30 mg / mL, about 5 mg / mL to about 20 mg / mL, about 5 mg / mL to about 10 mg / mL, about 10 mg / mL to about 100 mg / mL, about 10 mg / mL to about 75 mg / mL, about 10 mg / mL to about 50 mg / mL, about 10 mg / mL~about 40mg / mL, about 10mg / mL~about 30mg / mL, about 10mg / mL~about 20mg / mL, about 20mg / mL~about 100mg / mL, about 20mg / mL~about 75mg / mL mL, about 20 mg / mL to about 50 mg / mL, about 20 mg / mL to about 40 mg / mL, about 20 mg / mL to about 30 mg / mL, about 30 mg / mL to about 100 mg / mL, about 30 mg / m The concentration may be about 1 to about 75 mg / mL, about 30 mg / mL to about 50 mg / mL, about 30 mg / mL to about 40 mg / mL, about 40 mg / mL to about 100 mg / mL, about 40 mg / mL to about 75 mg / mL, about 40 mg / mL to about 50 mg / mL, about 50 mg / mL to about 100 mg / mL, about 50 mg / mL to about 75 mg / mL, or about 75 mg / mL to about 100 mg / mL.

[0063] In certain embodiments, the concentration of torsemide in the liquid pharmaceutical formulations described herein can be greater than about 0.5 mg / mL, greater than about 1 mg / mL, greater than about 5 mg / mL, greater than about 10 mg / mL, greater than about 20 mg / mL, greater than about 30 mg / mL, greater than about 40 mg / mL, greater than about 50 mg / mL, greater than about 60 mg / mL, greater than about 70 mg / mL, greater than about 80 mg / mL, greater than about 90 mg / mL, greater than about 100 mg / mL, or greater than about 125 mg / mL.

[0064] In certain embodiments, the concentration of torsemide in the liquid pharmaceutical formulations described herein can be about 0.5 mg / mL, about 1 mg / mL, about 2 mg / mL, about 3 mg / mL, about 4 mg / mL, about 5 mg / mL, about 6 mg / mL, about 7 mg / mL, about 8 mg / mL, about 9 mg / mL, about 10 mg / mL, about 11 mg / mL, about 12 mg / mL, about 13 mg / mL, about 14 mg / mL, about 15 mg / mL, about 16 mg / mL, about 17 mg / mL, about 18 mg / mL, about 19 mg / mL, about 20 mg / mL, about 25 mg / mL, about 30 mg / mL, about 35 mg / mL, about 40 mg / mL, about 45 mg / mL, about 50 mg / mL, about 60 mg / mL, about 70 mg / mL, about 80 mg / mL, about 90 mg / mL, about 100 mg / mL, or about 125 mg / mL.

[0065] pH, buffers and pH adjusters In certain embodiments, the pH of the liquid pharmaceutical formulations described herein can be about 5.5 to about 8.5, about 6 to about 8.5, about 6.5 to about 8.5, about 7 to about 8.5, about 7.5 to about 8.5, about 8 to about 8.5, about 5.5 to about 8, about 5.5 to about 7.5, about 5.5 to about 7, about 5.5 to about 6.5, about 5.5 to about 6, about 6 to about 8, about 6 to about 7.5, about 6 to about 7, about 6 to about 6.5, about 6.5 to about 8, about 6.5 to about 7.5, about 6.5 to about 7, about 7 to about 8, about 7 to about 7.5, or about 7.5 to about 8. In certain embodiments, the pH of the liquid pharmaceutical formulations described herein is about 6.5 to about 8.5.

[0066] In certain embodiments, the pH of the liquid pharmaceutical formulations described herein is about 7 to about 8.5, about 7.1 to about 8.5, about 7.3 to about 8.5, about 7.5 to about 8.5, about 7.7 to about 8.5, about 7.9 to about 8.5, about 8.1 to about 8.5, about 8.3 to about 8.5, about 7 to about 8.3, about 7 to about 8.1, about 7 to about 7.9, about 7 to about 7.7, about 7 to about 7.5, about 7 to about 7.3, about 7 to about 7.1, about 7.1 to about 8.3, about 7.1 to about 8.1, about 7.1 to about 8.1 It can be about 7.9, about 7.1 to about 7.7, about 7.1 to about 7.5, about 7.1 to about 7.3, about 7.3 to about 8.3, about 7.3 to about 8.1, about 7.3 to about 7.9, about 7.3 to about 7.7, about 7.3 to about 7.5, about 7.5 to about 8.3, about 7.5 to about 8.1, about 7.5 to about 7.9, about 7.5 to about 7.7, about 7.7 to about 8.3, about 7.7 to about 8.1, about 7.7 to about 7.9, about 7.9 to about 8.3, about 7.9 to about 8.1, or about 8.1 to about 8.3.

[0067] In certain embodiments, the pH of the liquid pharmaceutical formulations described herein can be about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, about 8, about 8.1, about 8.2, about 8.3, about 8.4, or about 8.5. In certain embodiments, the pH of the liquid pharmaceutical formulations described herein can be about 7.4. In certain embodiments, the pH of the liquid pharmaceutical formulations described herein can be about 7.7.

[0068] In certain embodiments, the pH of the liquid pharmaceutical formulations described herein is 5.5±0.3, 5.6±0.3, 5.7±0.3, 5.8±0.3, 5.9±0.3, 6±0.3, 6.1±0.3, 6.2±0.3, 6.3±0.3, 6.4±0.3, 6.5±0.3, 6.6±0.3, 6.7±0.3, 6.8±0.3. The pH of the liquid pharmaceutical formulations described herein may be 7.4±0.3, 6.9±0.3, 7±0.3, 7.1±0.3, 7.2±0.3, 7.3±0.3, 7.4±0.3, 7.5±0.3, 7.6±0.3, 7.7±0.3, 7.8±0.3, 7.9±0.3, 8±0.3, 8.1±0.3, 8.2±0.3, 8.3±0.3, 8.4±0.3, or 8.5±0.3. In certain embodiments, the pH of the liquid pharmaceutical formulations described herein may be 7.4±0.3. In certain embodiments, the pH of the liquid pharmaceutical formulations described herein may be 7.7±0.3.

[0069] (i) a pharmaceutically acceptable buffer solution In certain embodiments, the concentration of the pharmaceutically acceptable buffer in the liquid pharmaceutical formulation described herein is from about 10 mM to about 500 mM, from about 20 mM to about 500 mM, from about 30 mM to about 500 mM, from about 40 mM to about 500 mM, from about 50 mM to about 500 mM, from about 60 mM to about 500 mM, from about 70 mM to about 500 mM, from about 80 mM to about 500 mM, from about 90 mM to about 500 mM, from about 100 mM to about 500 mM, from about 125 mM to about 500 mM, from about 150 mM to about 500 mM, from about 200 mM to about 500 mM, from about 250 mM to about 500 mM, from about 300 mM to about 500 mM, 350 mM to about 500 mM, about 400 mM to about 500 mM, about 450 mM to about 500 mM, about 10 mM to about 450 mM, about 10 mM to about 400 mM, about 10 mM to about 350 mM, about 10 mM to about 300 mM, about 10 mM to about 250 mM, about 10 mM to about 200 mM, about 10 mM ~150mM, 10mM~125mM, 10mM~100mM, 10mM~90mM, 10m~80mM, 10m M ~ about 70mM, about 10mM - about 60mM, about 10mM - about 50mM, about 10mM - about 40mM, about 10mM - about 30mM, about 10mM - about 20mM, about 20mM to about 450mM, about 20mM to about 400mM, about 20mM to about 350mM, about 20mM to about 300mM, about 20mM ~about 250mM, about 20mM to about 200mM, about 20mM to about 150mM, about 20mM to about 100mM, about 20mM to about 90mM, about 20 mM~about 80mM, about 20mM~about 70mM, about 20mM~about 60mM, about 20mM~about 50mM, about 20mM~about 40mM, about 20mM ~30mM, approximately 30mM~450mM, approximately 30mM~400mM, approximately 30mM~350mM, approximately 30mM~300mM, approximately 30m M ~ about 250mM, about 30mM - about 200mM, about 30mM - about 150mM, about 30mM - about 125mM, about 30mM - about 100mM, about 30mM to about 90mM, about 30mM to about 80mM, about 30mM to about 70mM, about 30mM to about 60mM, about 30mM to about 50mM, about 30m M ~ about 40mM, about 40mM - about 450mM, about 40mM - about 400mM, about 40mM - about 350mM, about 40mM - about 300mM, about 4 0mM to about 250mM, about 40mM to about 200mM, about 40mM to about 150mM, about 40mM to about 125mM, about 40mM to about 100mM,about 40mM to about 90mM, about 40mM to about 80mM, about 40mM to about 70mM, about 40mM to about 60mM, about 40mM to about 50mM, about 50mM to about 450mM, about 50mM to about 400mM, about 50mM to about 350mM, about 50mM to about 300mM, about 50mM to about 250mM, about 50mM to about 200mM, about 50mM to about 150mM, about 50mM to about 125mM, about 50mM to about 100mM, about 50mM to about 90mM, about 50mM to about 80mM, about 50mM to about 70mM, about 50mM to about 60mM, about 60mM to about 450mM, about 60mM to about 400mM, about 60mM to about 350mM, about 60mM to about 300mM, about 60mM to about 250mM, about 60mM to about 200mM, about 60mM to about 150mM, about 60mM to about 125mM, about 60mM to about 100mM, about 60mM to about 90mM, about 60mM to about 80mM, about 60mM to about 70mM, about 70mM to about 450mM, about 70mM to about 400mM, about 70mM to about 350mM, about 70mM to about 300mM, about 70mM to about 250mM, about 70mM to about 200mM, about 70mM to about 150mM, about 70mM to about 100mM, about 70mM to about 90mM, about 70mM to about 80mM , about 80mM to about 450mM, about 80mM to about 400mM, about 80mM to about 350mM, about 80mM to about 300mM, about 80mM to about 250mM, about 80mM to about 200mM, about 80mM to about 150mM, about 80mM to about 100mM, about 80mM to about 90mM, about 90mM to about 450mM, about 90mM to about 400mM, about 90mM to about 350mM, about 90mM to about 300mM, about 90mM to about 250mM, about 90mM to about 200mM, about 90mM to about 150mM, about 90mM to about 100mM, about 100mM to about 450mM , about 100mM to about 400mM, about 100mM to about 350mM, about 100mM to about 300mM, about 100mM to about 250mM, about 100mM to about 200mM, about 100mM to about 150mM, about 150mM to about 450mM, about 150mM to about 400mM, about 150mM to about 350mM , about 150mM to about 300mM, about 150mM to about 250mM, about 150mM to about 200mM, about 200mM to about 450mM, about 200mM to about 400mM, about 200mM to about 350mM, about 200mM to about 300mM, about 200mM to about 250mM, about 250mM to about 450mM,The concentration of the pharmaceutically acceptable buffer in the liquid pharmaceutical formulation described herein can be about 250 mM to about 400 mM, about 250 mM to about 350 mM, about 250 mM to about 300 mM, about 300 mM to about 450 mM, about 300 mM to about 400 mM, about 300 mM to about 350 mM, about 350 mM to about 450 mM, about 350 mM to about 400 mM, or about 400 mM to about 450 mM. In certain embodiments, the concentration of the pharmaceutically acceptable buffer in the liquid pharmaceutical formulation described herein can be about 50 mM to about 125 mM.

[0070] In certain embodiments, the concentration of the pharmaceutically acceptable buffer in the liquid pharmaceutical formulations described herein is about 10 mM, about 15 mM, about 20 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, about 45 mM, about 50 mM, about 55 mM, about 60 mM, about 65 mM, about 70 mM, about 75 mM, about 80 mM, about 85 mM, about 90 mM, about 95 mM, about 100 mM, about 105 mM, about 110 mM, The concentration of the pharmaceutically acceptable buffer in the liquid pharmaceutical formulation described herein may be about 115 mM, about 120 mM, about 125 mM, about 130 mM, about 135 mM, about 140 mM, about 145 mM, about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, about 200 mM, about 225 mM, about 250 mM, about 275 mM, about 300 mM, about 325 mM, about 350 mM, about 375 mM, about 400 mM, about 425 mM, about 450 mM, about 475 mM, or about 500 mM. In certain embodiments, the concentration of the pharmaceutically acceptable buffer in the liquid pharmaceutical formulation described herein may be about 50 mM. In certain embodiments, the concentration of the pharmaceutically acceptable buffer in the liquid pharmaceutical formulation described herein may be about 125 mM.

[0071] In certain embodiments, the concentration of the pharmaceutically acceptable buffer in the liquid pharmaceutical formulations described herein can be about 10 mM or less, about 20 mM or less, about 30 mM or less, about 40 mM or less, about 50 mM or less, about 60 mM or less, about 70 mM or less, about 80 mM or less, about 90 mM or less, about 100 mM or less, about 125 mM or less, about 150 mM or less, about 175 mM or less, about 200 mM or less, about 225 mM or less, about 250 mM or less, about 275 mM or less, about 300 mM or less, about 325 mM or less, about 350 mM or less, about 375 mM or less, about 400 mM or less, about 425 mM or less, about 450 mM or less, about 475 mM or less, or about 500 mM or less.

[0072] In certain embodiments, the pharmaceutically acceptable buffer comprises a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and any combination thereof. In certain embodiments, the buffering agent is histidine. In certain embodiments, the buffering agent is citrate. In certain embodiments, the buffering agent is sodium phosphate. In certain embodiments, the buffering agent is potassium phosphate. In certain embodiments, the buffering agent is tromethamine or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutically acceptable salt of tromethamine is tromethamine hydrochloride.

[0073] In certain embodiments, the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulation described herein is from about 10 mM to about 250 mM, from about 15 mM to about 250 mM, from about 20 mM to about 250 mM, from about 25 mM to about 250 mM, from about 30 mM to about 250 mM, from about 40 mM to about 250 mM, from about 50 mM to about 250 mM, from about 60 mM to about 250 mM, from about 70 mM to about 250 mM, from about 80 mM to about 250 mM, from about 90 mM to about 250 mM, from about 100 mM to about 250 mM, from about 125 mM to about 250 mM, from about 150 mM to about 250 mM, or from about 175 mM. ~about 250mM, about 200mM to about 250mM, about 225mM to about 250mM, about 10mM to about 225mM, about 10mM to about 200mM, Approximately 10mM to approximately 175mM, approximately 10mM to approximately 150mM, approximately 10mM to approximately 125mM, approximately 10mM to approximately 100mM, approximately 10mM to approximately 90m M, about 10mM to about 80mM, about 10mM to about 70mM, about 10mM to about 60mM, about 10mM to about 50mM, about 10mM to about 40mM, Approximately 10mM to approximately 30mM, approximately 10mM to approximately 25mM, approximately 10mM to approximately 20mM, approximately 10mM to approximately 15mM, approximately 15mM to approximately 225mM, approximately 15mM to about 200mM, about 15mM to about 175mM, about 15mM to about 150mM, about 15mM to about 125mM, about 15mM to about 100m M, about 15mM to about 90mM, about 15mM to about 80mM, about 15mM to about 70mM, about 15mM to about 60mM, about 15mM to about 50mM, Approximately 15mM to approximately 40mM, approximately 15mM to approximately 30mM, approximately 15mM to approximately 25mM, approximately 15mM to approximately 20mM, approximately 20mM to approximately 225mM, approximately 20mM to about 200mM, about 20mM to about 175mM, about 20mM to about 150mM, about 20mM to about 125mM, about 20mM to about 100m M, about 20mM to about 90mM, about 20mM to about 80mM, about 20mM to about 70mM, about 20mM to about 60mM, about 20mM to about 50mM, Approximately 20mM to approximately 40mM, approximately 20mM to approximately 30mM, approximately 20mM to approximately 25mM, approximately 25mM to approximately 225mM, approximately 25mM to approximately 200mM, Approximately 25mM to approximately 175mM, approximately 25mM to approximately 150mM, approximately 25mM to approximately 125mM, approximately 25mM to approximately 100mM, approximately 25mM to approximately 90m M, about 25mM to about 80mM, about 25mM to about 70mM, about 25mM to about 60mM, about 25mM to about 50mM, about 25mM to about 40mM,about 25mM to about 30mM, about 30mM to about 225mM, about 30mM to about 200mM, about 30mM to about 175mM, about 30mM to about 150mM, about 30mM to about 125mM, about 30mM to about 100mM, about 30mM to about 90mM, about 30mM to about 80mM, about 30mM to about 70mM , about 30mM to about 60mM, about 30mM to about 50mM, about 30mM to about 40mM, about 40mM to about 225mM, about 40mM to about 200mM, about 40mM to about 175mM, about 40mM to about 150mM, about 40mM to about 125mM, about 40mM to about 100mM, about 40mM to about 90mM , about 40mM to about 80mM, about 40mM to about 70mM, about 40mM to about 60mM, about 40mM to about 50mM, about 50mM to about 225mM, about 50mM to about 200mM, about 50mM to about 175mM, about 50mM to about 150mM, about 50mM to about 125mM, about 50mM to about 100mM M, about 50 mM to about 90 mM, about 50 mM to about 80 mM, about 50 mM to about 70 mM, about 50 mM to about 60 mM, about 60 mM to about 225 mM, about 60 mM to about 200 mM, about 60 mM to about 175 mM, about 60 mM to about 150 mM, about 60 mM to about 125 mM, about 60 mM to about 100 mM M, about 60mM to about 90mM, about 60mM to about 80mM, about 60mM to about 70mM, about 60mM to about 60mM, about 70mM to about 225mM, about 70mM to about 200mM, about 70mM to about 175mM, about 70mM to about 150mM, about 70mM to about 125mM, about 70mM to about 100mM, about 70mM to about 90mM, about 70mM to about 80mM, about 80mM to about 225mM, about 80mM to about 200mM, about 80mM to about 175mM, about 80mM to about 150mM, about 80mM to about 125mM, about 80mM to about 100mM, about 80mM to about 90mM, about 90mM to about 225mM, about 90mM to about 200mM, about 90mM to about 175mM, about 90mM to about 150mM, about 90mM to about 125mM, about 90mM to about 100mM, about 100mM to about 225mM, about 100mM to about 200mM, about 100mM to about 175mM, about 100mM to about 150mM, about 100mM to about 125mM, about 125mM to about 225mM, about 125mM to about 200mM, about 125mM to about 175mM, about 125mM to about 150mM, about 150mM to about 225mM, about 150mM to about 200mM, about 150mM to about 175mM,The concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulation described herein may be about 150 mM to about 250 mM, about 175 mM to about 225 mM, about 175 mM to about 200 mM, or about 200 mM to about 225 mM. In certain embodiments, the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulation described herein is about 10 mM to about 200 mM. In certain embodiments, the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulation described herein is about 25 mM to about 150 mM. In certain embodiments, the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulation described herein is about 50 mM to about 125 mM.

[0074] In certain embodiments, the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulations described herein is about 10 mM, about 11 mM, about 12 mM, about 13 mM, about 14 mM, about 15 mM, about 16 mM, about 17 mM, about 18 mM, about 19 mM, about 20 mM, about 21 mM, about 22 mM, about 23 mM, about 24 mM, about 25 mM, about 26 mM, about 27 mM, about 28 mM, about 29 mM, about 30 mM, about 32 mM, about 34 mM, about 36 mM, , about 38 mM, about 40 mM, about 45 mM, about 50 mM, about 55 mM, about 60 mM, about 65 mM, about 70 mM, about 75 mM, about 80 mM, about 85 mM, about 90 mM, about 95 mM, about 100 mM, about 105 mM, about 110 mM, about 115 mM, about 120 mM, about 125 mM, about 130 mM, about 140 mM, about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, about 200 mM, about 225 mM, or about 250 mM. In certain embodiments, the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulations described herein may be about 50 mM. In certain embodiments, the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulations described herein may be about 125 mM.

[0075] In certain embodiments, the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulations described herein can be about 10 mM or less, about 20 mM or less, about 30 mM or less, about 40 mM or less, about 50 mM or less, about 60 mM or less, about 70 mM or less, about 80 mM or less, about 90 mM or less, about 100 mM or less, about 125 mM or less, about 150 mM or less, about 175 mM or less, about 200 mM or less, about 225 mM or less, or about 250 mM or less.

[0076] (ii) pH adjuster In certain embodiments, the liquid pharmaceutical formulations described herein further comprise a pharmaceutically acceptable pH adjusting agent.

[0077] Exemplary pharmaceutically acceptable pH adjusting agents include, but are not limited to, one or more of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, and trolamine.

[0078] In certain embodiments, the pharmaceutically acceptable pH adjusting agent is selected from the group consisting of potassium hydroxide, sodium hydroxide, hydrochloric acid, and combinations thereof. In certain embodiments, the pharmaceutically acceptable pH adjusting agent is hydrochloric acid and sodium hydroxide. In certain embodiments, the pharmaceutically acceptable pH adjusting agent is sodium hydroxide. In certain embodiments, the pharmaceutically acceptable pH adjusting agent is potassium hydroxide. In certain embodiments, the pharmaceutically acceptable pH adjusting agent is hydrochloric acid.

[0079] antioxidants In certain embodiments, the liquid pharmaceutical formulations described herein may further comprise an antioxidant.

[0080] In certain embodiments, the amount of antioxidant in the liquid pharmaceutical formulations described herein is from about 0.01% (w / w) to about 2% (w / w), from about 0.05% (w / w) to about 2% (w / w), from about 0.1% (w / w) to about 2% (w / w), from about 0.2% (w / w) to about 2% (w / w), from about 0.3% (w / w) to about 2% (w / w), from about 0.4% (w / w) to about 2% (w / w), from about 0.5% (w / w) to about 2% (w / w), from about 0.6% (w / w) to about 2% (w / w), from about 0.7% (w / w) to about 2% (w / w), from about 0.8% (w / w) to about 2% (w / w), or about 0.9% (w / w). ~ about 2% (w / w), about 1% (w / w) ~ about 2% (w / w), about 1.1% (w / w) ~ about 2% (w / w), about 1.2% (w / w) ~ about 2% (w / w), about 1.3% (w / w) ~ about 2% (w / w), about 1.4% (w / w) ~ about 2% (w / w), about 1.5% (w / w) ~ about 2% (w / w), about 1.6% (w / w) to about 2% (w / w), about 1.7% (w / w) to about 2% (w / w), about 1.8% (w / w) to about 2% (w / w), about 1.9% (w / w) to about 2% (w / w), about 0.01% (w / w) to about 1.9% (w / w), about 0.01% (w / w) to about 1.8% (w / w), about 0.01% (w / w) to about 1.7% (w / w), about 0.01% (w / w) to about 1.6% (w / w), about 0.01% (w / w) to about 1.5% (w / w), about 0.01% (w / w) to about 1.4% (w / w), about 0.01% (w / w) to about 1.3% (w / w), about 0.01% (w / w) to about 1.2% (w / w), about 0.01% (w / w) to about 1.1% (w / w), about 0.01% (w / w) to about 1% (w / w), about 0.01% (w / w) to about 0.9% (w / w), about 0.01% (w / w) to about 0.8% (w / w), about 0.01% (w / w) to about 0.7% ( w / w), about 0.01% (w / w) to about 0.6% (w / w), about 0.01% (w / w) to about 0.5% (w / w), about 0.01% (w / w) to about 0.4% (w / w), about 0.01% (w / w) to about 0.3% (w / w), about 0.01% (w / w) to about 0.2% (w / w), about 0.01 % (w / w) to approximately 0.1% (w / w), approximately 0.01% (w / w) to approximately 0.05% (w / w), approximately 0.05% (w / w) to approximately 1.9% (w / w), approximately 0.05% (w / w) to approximately 1.8% (w / w), approximately 0.05% (w / w) to approximately 1.7% (w / w), approximately 0.05% (w / w) to approximately 1.6% (w / w), about 0.05% (w / w) to about 1.5% (w / w), about 0.05% (w / w) to about 1.4% (w / w), about 0.05% (w / w) to about 1.3% (w / w), about 0.05% (w / w) to about 1.2% (w / w), about 0.05% (w / w) to about 1.1% (w / w), about 0.05% (w / w) to approximately 1% (w / w), approximately 0.05% (w / w) to approximately 0.9% (w / w), approximately 0.05% (w / w) to approximately 0.8% (w / w), approximately 0.05% (w / w) to approximately 0.7% (w / w), approximately 0.05% (w / w) to approximately 0.6% (w / w), approximately 0.05% (w / w) to approximately 0.5% (w / w), approximately 0.05% (w / w) to approximately 0.4% (w / w), approximately 0.05% (w / w) to approximately 0.3% (w / w), approximately 0.05% (w / w) to approximately 0.2% (w / w), approximately 0.05% (w / w) to approximately 0.1% (w / w), approximately 0.1% (w / w) to approximately 1.9% (w / w), approximately 0.1% (w / w) to approximately 1.8% (w / w), approximately 0.1% (w / w) to approximately 1.7% (w / w), approximately 0.1% (w / w) to approximately 1.6% (w / w), approximately 0.1% (w / w) to approximately 1.5% (w / w), approximately 0.1% (w / w) to approximately 1.4% (w / w), approximately 0.1% (w / w) to approximately 1.3% (w / w), about 0.1% (w / w) to about 1.2% (w / w), about 0.1% (w / w) to about 1.1% (w / w), about 0.1% (w / w) to about 1% (w / w), about 0.1% (w / w) to about 0.9% (w / w), about 0.1% (w / w) to about 0.8% (w / w), about 0.1% (w / w) Approximately 0.7% (w / w), approximately 0.1% (w / w) to approximately 0.6% (w / w), approximately 0.1% (w / w) to approximately 0.5% (w / w), approximately 0.1% (w / w) to approximately 0.4% (w / w), approximately 0.1% (w / w) to approximately 0.3% (w / w), approximately 0.1% (w / w) to approximately 0.2% (w / w), approximately 0.2 %(w / w) to about 1.9%(w / w), about 0.2%(w / w) to about 1.8%(w / w), about 0.2%(w / w) to about 1.7%(w / w), about 0.2%(w / w) to about 1.6%(w / w), about 0.2%(w / w) to about 1.5%(w / w), about 0.2%(w / w) to about 1.4%(w / w), about 0.2% (w / w) to about 1.3% (w / w), about 0.2% (w / w) to about 1.2% (w / w), about 0.2% (w / w) to about 1.1% (w / w), about 0.2% (w / w) to about 1% (w / w), about 0.2% (w / w) to about 0.9% (w / w), about 0.2% (w / w) to about 0.8% (w / w), about 0.2% (w / w) to about 0.7% (w / w), about 0.2% (w / w) to about 0.6% (w / w), about 0.2% (w / w) to about 0.5% (w / w), about 0.2% (w / w) to about 0.4% (w / w), about 0.2% (w / w) to about 0.3% (w / w), about 0.3% ( (w / w) to about 1.9% (w / w), about 0.3% (w / w) to about 1.8% (w / w), about 0.3% (w / w) to about 1.7% (w / w), about 0.3% (w / w) to about 1.6% (w / w), about 0.3% (w / w) to about 1.5% (w / w), about 0.3% (w / w) to about 1.4% (w / w) , about 0.3% (w / w) to about 1.3% (w / w), about 0.3% (w / w) to about 1.2% (w / w), about 0.3% (w / w) to about 1.1% (w / w), about 0.3% (w / w) to about 1% (w / w), about 0.3% (w / w) to about 0.9% (w / w), about 0.3% (w / w) to about 0.8 % (w / w), about 0.3% (w / w) to about 0.7% (w / w), about 0.3% (w / w) to about 0.6% (w / w), about 0.3% (w / w) to about 0.5% (w / w), about 0.3% (w / w) to about 0.4% (w / w), about 0.4% (w / w) to about 1.9% (w / w), about 0.4% (w / (w / w) to about 1.8% (w / w), about 0.4% (w / w) to about 1.7% (w / w), about 0.4% (w / w) to about 1.6% (w / w), about 0.4% (w / w) to about 1.5% (w / w), about 0.4% (w / w) to about 1.4% (w / w), about 0.4% (w / w) to about 1.3% (w / w), Approximately 0.4% (w / w) to approximately 1.2% (w / w), approximately 0.4% (w / w) to approximately 1.1% (w / w), approximately 0.4% (w / w) to approximately 1% (w / w), approximately 0.4% (w / w) to approximately 0.9% (w / w), approximately 0.4% (w / w) to approximately 0.8% (w / w), approximately 0.4% (w / w) to approximately 0.7% ( (w / w), about 0.4% (w / w) to about 0.6% (w / w), about 0.4% (w / w) to about 0.5% (w / w), about 0.5% (w / w) to about 1.9% (w / w), about 0.5% (w / w) to about 1.8% (w / w), about 0.5% (w / w) to about 1.7% (w / w), about 0.5% (w / w) ~ approximately 1.6% (w / w), approximately 0.5% (w / w) ~ approximately 1.5% (w / w), approximately 0.5% (w / w) ~ approximately 1.4% (w / w), approximately 0.5% (w / w) ~ approximately 1.3% (w / w), approximately 0.5% (w / w) ~ approximately 1.2% (w / w), approximately 0.5% (w / w) ~ approximately 1.1% (w / w), approximately 0.5% (w / w) to approximately 1% (w / w), approximately 0.5% (w / w) to approximately 0.9% (w / w), approximately 0.5% (w / w) to approximately 0.8% (w / w), approximately 0.5% (w / w) to approximately 0.7% (w / w), approximately 0.5% (w / w) to approximately 0.6% (w / w), approximately 0.6% (w / w) to approximately 1.9% (w / w), about 0.6% (w / w) to about 1.8% (w / w), about 0.6% (w / w) to about 1.7% (w / w), about 0.6% (w / w) to about 1.6% (w / w), about 0.6% (w / w) to about 1.5% (w / w), about 0.6% (w / w) to about 1.4% (w / w), about 0.6% (w / w) to Approximately 1.3% (w / w), approximately 0.6% (w / w) to approximately 1.2% (w / w), approximately 0.6% (w / w) to approximately 1.1% (w / w), approximately 0.6% (w / w) to approximately 1% (w / w), approximately 0.6% (w / w) to approximately 0.9% (w / w), approximately 0.6% (w / w) to approximately 0.8% (w / w), approximately 0.6% (w / w) to about 0.7% (w / w), about 0.7% (w / w) to about 1.9% (w / w), about 0.7% (w / w) to about 1.8% (w / w), about 0.7% (w / w) to about 1.7% (w / w), about 0.7% (w / w) to about 1.6% (w / w), about 0.7% (w / w) to about 1.5% (w / w), about 0.7% (w / w) to about 1.4% (w / w), about 0.7% (w / w) to about 1.3% (w / w), about 0.7% (w / w) to about 1.2% (w / w), about 0.7% (w / w) to about 1.1% (w / w), about 0.7% (w / w) to about 1% (w / w), about 0.7% (w / w) to about 0 0.9% (w / w), approximately 0.7% (w / w) to approximately 0.8% (w / w), approximately 0.8% (w / w) to approximately 1.9% (w / w), approximately 0.8% (w / w) to approximately 1.8% (w / w), approximately 0.8% (w / w) to approximately 1.7% (w / w), approximately 0.8% (w / w) to approximately 1.6% (w / w), approximately 0.8% (w / w) to about 1.5% (w / w), about 0.8% (w / w) to about 1.4% (w / w), about 0.8% (w / w) to about 1.3% (w / w), about 0.8% (w / w) to about 1.2% (w / w), about 0.8% (w / w) to about 1.1% (w / w), about 0.8% (w / w) to about 1% (w / w) , about 0.8% (w / w) to about 0.9% (w / w), about 0.9% (w / w) to about 1.9% (w / w), about 0.9% (w / w) to about 1.8% (w / w), about 0.9% (w / w) to about 1.7% (w / w), about 0.9% (w / w) to about 1.6% (w / w), about 0.9% (w / w) to about 1.5% (w / w), approximately 0.9% (w / w) to approximately 1.4% (w / w), approximately 0.9% (w / w) to approximately 1.3% (w / w), approximately 0.9% (w / w) to approximately 1.2% (w / w), approximately 0.9% (w / w) to approximately 1.1% (w / w), approximately 0.9% (w / w) to approximately 1% (w / w), approximately 1% (w / w) ~ approximately 1.9% (w / w), approximately 1% (w / w) ~ approximately 1.8% (w / w), approximately 1% (w / w) ~ approximately 1.7% (w / w), approximately 1% (w / w) ~ approximately 1.6% (w / w), approximately 1% (w / w) ~ approximately 1.5% (w / w), approximately 1% (w / w) ~ approximately 1.4% (w / w), approximately 1% (w / w) ~ approximately 1. 3% (w / w), approximately 1% (w / w) to approximately 1.2% (w / w), approximately 1% (w / w) to approximately 1.1% (w / w), approximately 1.1% (w / w) to approximately 1.9% (w / w), approximately 1.1% (w / w) to approximately 1.8% (w / w), approximately 1.1% (w / w) to approximately 1.7% (w / w), approximately 1.1% (w / w) ~ about 1.6% (w / w), about 1.1% (w / w) to about 1.5% (w / w), about 1.1% (w / w) to about 1.4% (w / w), about 1.1% (w / w) to about 1.3% (w / w), about 1.1% (w / w) to about 1.2% (w / w), about 1.2% (w / w) to about 1.9% (w / w), about 1 0.2% (w / w) to approximately 1.8% (w / w), approximately 1.2% (w / w) to approximately 1.7% (w / w), approximately 1.2% (w / w) to approximately 1.6% (w / w), approximately 1.2% (w / w) to approximately 1.5% (w / w), approximately 1.2% (w / w) to approximately 1.4% (w / w), approximately 1.2% (w / w) to approximately 1.3% (w / w), about 1.3% (w / w) to about 1.9% (w / w), about 1.3% (w / w) to about 1.8% (w / w), about 1.3% (w / w) to about 1.7% (w / w), about 1.3% (w / w) to about 1.6% (w / w), about 1.3% (w / w) to about 1.5% (w / w), about 1.3% (w / (w / w) to about 1.4% (w / w), about 1.4% (w / w) to about 1.9% (w / w), about 1.4% (w / w) to about 1.8% (w / w), about 1.4% (w / w) to about 1.7% (w / w), about 1.4% (w / w) to about 1.6% (w / w), about 1.4% (w / w) to about 1.5% (w / w), Approximately 1.5% (w / w) to approximately 1.9% (w / w), approximately 1.5% (w / w) to approximately 1.8% (w / w), approximately 1.5% (w / w) to approximately 1.7% (w / w), approximately 1.5% (w / w) to approximately 1.6% (w / w), approximately 1.6% (w / w) to approximately 1.9% (w / w), approximately 1.6% (w / w) to approximately 1.In certain embodiments, the antioxidant content in the liquid pharmaceutical formulations described herein may be about 8% (w / w), about 1.6% (w / w) to about 1.7% (w / w), about 1.7% (w / w) to about 1.9% (w / w), about 1.7% (w / w) to about 1.8% (w / w), or about 1.8% (w / w) to about 1.9% (w / w). The amount of antioxidant can be from about 0.01% (w / w) to about 0.3% (w / w). In certain embodiments, the amount of antioxidant in the liquid pharmaceutical formulations described herein can be from about 0.05% (w / w) to about 2% (w / w).

[0081] In certain embodiments, the amount of antioxidant in the liquid pharmaceutical formulations described herein is about 0.05% (w / w), about 0.1% (w / w), about 0.2% (w / w), about 0.3% (w / w), about 0.4% (w / w), about 0.5% (w / w), about 0.6% (w / w), about 0.7% (w / w), about 0.8% (w / w), about It can be 0.9% (w / w), about 1.0% (w / w), about 1.1% (w / w), about 1.2% (w / w), about 1.3% (w / w), about 1.4% (w / w), about 1.5% (w / w), about 1.6% (w / w), about 1.7% (w / w), about 1.8% (w / w), about 1.9% (w / w), or about 2.0% (w / w). In certain embodiments, the amount of antioxidant in the liquid pharmaceutical formulations described herein can be about 0.3% (w / w).

[0082] In certain embodiments, the antioxidant is selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof. In certain embodiments, the antioxidant is sodium disulfite. In certain embodiments, the antioxidant is sodium bisulfite monothioglycerol. In certain embodiments, the antioxidant is methionine. In certain embodiments, the antioxidant is EDTA.

[0083] In certain embodiments, the amount of sodium disulfite in the liquid pharmaceutical formulations described herein is from about 0.01% (w / w) to about 2% (w / w), from about 0.05% (w / w) to about 2% (w / w), from about 0.1% (w / w) to about 2% (w / w), from about 0.2% (w / w) to about 2% (w / w), from about 0.3% (w / w) to about 2% (w / w), from about 0.4% (w / w) to about 2% (w / w), from about 0.5% (w / w) to about 2% (w / w), from about 0.6% (w / w) to about 2% (w / w), from about 0.7% (w / w) to about 2% (w / w), from about 0.8% (w / w) to about 2% (w / w), or from about 0. 9% (w / w) to approximately 2% (w / w), approximately 1% (w / w) to approximately 2% (w / w), approximately 1.1% (w / w) to approximately 2% (w / w), approximately 1.2% (w / w) to approximately 2% (w / w), approximately 1.3% (w / w) to approximately 2% (w / w), approximately 1.4% (w / w) to approximately 2% (w / w), approximately 1.5% (w / w) ) to about 2% (w / w), about 1.6% (w / w) to about 2% (w / w), about 1.7% (w / w) to about 2% (w / w), about 1.8% (w / w) to about 2% (w / w), about 1.9% (w / w) to about 2% (w / w), about 0.01% (w / w) to about 1.9% (w / w), about 0.01% (w / w) ~ about 1.8% (w / w), about 0.01% (w / w) to about 1.7% (w / w), about 0.01% (w / w) to about 1.6% (w / w), about 0.01% (w / w) to about 1.5% (w / w), about 0.01% (w / w) to about 1.4% (w / w), about 0.01% (w / w) to about 1.3% (w / w), about 0.01% (w / w) to about 1.2% (w / w), about 0.01% (w / w) to about 1.1% (w / w), about 0.01% (w / w) to about 1% (w / w), about 0.01% (w / w) to about 0.9% (w / w), about 0.01% (w / w) to about 0.8% (w / w), about 0.01% (w / w) to about 0.7% (w / w), about 0.01% (w / w) to about 0.6% (w / w), about 0.01% (w / w) to about 0.5% (w / w), about 0.01% (w / w) to about 0.4% (w / w), about 0.01% (w / w) to about 0.3% (w / w), about 0.01% (w / w) to about 0.2% (w / w), approximately 0.01% (w / w) to approximately 0.1% (w / w), approximately 0.01% (w / w) to approximately 0.05% (w / w), approximately 0.05% (w / w) to approximately 1.9% (w / w), approximately 0.05% (w / w) to approximately 1.8% (w / w), approximately 0.05% (w / w) to approximately 1.7% (w / w), approximately 0.0.05% (w / w) to about 1.6% (w / w), about 0.05% (w / w) to about 1.5% (w / w), about 0.05% (w / w) to about 1.4% (w / w), about 0.05% (w / w) to about 1.3% (w / w), about 0.05% (w / w) to about 1.2% (w / w), about 0.05% (w / w) to about 1.1% (w / w), about 0.05% (w / w) to about 1% (w / w), about 0.05% (w / w) to about 0.9% (w / w), about 0.05% (w / w) to about 0.8% (w / w), about 0.05% (w / w) to about 0.7% (w / w), about 0.05% (w / w) to about 0.6% (w / w), about 0 0.05% (w / w) to approximately 0.5% (w / w), approximately 0.05% (w / w) to approximately 0.4% (w / w), approximately 0.05% (w / w) to approximately 0.3% (w / w), approximately 0.05% (w / w) to approximately 0.2% (w / w), approximately 0.05% (w / w) to approximately 0.1% (w / w), approximately 0.1% (w / w) to approximately 1.9% (w / w), approximately 0.1% (w / w) to approximately 1.8% (w / w), approximately 0.1% (w / w) to approximately 1.7% (w / w), approximately 0.1% (w / w) to approximately 1.6% (w / w), approximately 0.1% (w / w) to approximately 1.5% (w / w), approximately 0.1% (w / w) to approximately 1.4% (w / w), approximately 0.1% (w / w) to about 1.3% (w / w), about 0.1% (w / w) to about 1.2% (w / w), about 0.1% (w / w) to about 1.1% (w / w), about 0.1% (w / w) to about 1% (w / w), about 0.1% (w / w) to about 0.9% (w / w), about 0.1% (w / w) to about 0.8% (w / w), Approximately 0.1% (w / w) to approximately 0.7% (w / w), approximately 0.1% (w / w) to approximately 0.6% (w / w), approximately 0.1% (w / w) to approximately 0.5% (w / w), approximately 0.1% (w / w) to approximately 0.4% (w / w), approximately 0.1% (w / w) to approximately 0.3% (w / w), approximately 0.1% (w / w) to approximately 0.2 % (w / w), about 0.2% (w / w) to about 1.9% (w / w), about 0.2% (w / w) to about 1.8% (w / w), about 0.2% (w / w) to about 1.7% (w / w), about 0.2% (w / w) to about 1.6% (w / w), about 0.2% (w / w) to about 1.5% (w / w), about 0.2% (w / (w / w) to about 1.4% (w / w), about 0.2% (w / w) to about 1.3% (w / w), about 0.2% (w / w) to about 1.2% (w / w), about 0.2% (w / w) to about 1.1% (w / w), about 0.2% (w / w) to about 1% (w / w), about 0.2% (w / w) to about 0.9% (w / w), about 0.2% (w / w) to approximately 0.8% (w / w), approximately 0.2% (w / w) to approximately 0.7% (w / w), approximately 0.2% (w / w) to approximately 0.6% (w / w), approximately 0.2% (w / w) to approximately 0.5% (w / w), approximately 0.2% (w / w) to approximately 0.4% (w / w), approximately 0.2% (w / w) to approximately 0.3% ( w / w), about 0.3% (w / w) to about 1.9% (w / w), about 0.3% (w / w) to about 1.8% (w / w), about 0.3% (w / w) to about 1.7% (w / w), about 0.3% (w / w) to about 1.6% (w / w), about 0.3% (w / w) to about 1.5% (w / w), about 0.3% (w / w) ~ about 1.4% (w / w), about 0.3% (w / w) to about 1.3% (w / w), about 0.3% (w / w) to about 1.2% (w / w), about 0.3% (w / w) to about 1.1% (w / w), about 0.3% (w / w) to about 1% (w / w), about 0.3% (w / w) to about 0.9% (w / w), about 0.3 %(w / w) to about 0.8%(w / w), about 0.3%(w / w) to about 0.7%(w / w), about 0.3%(w / w) to about 0.6%(w / w), about 0.3%(w / w) to about 0.5%(w / w), about 0.3%(w / w) to about 0.4%(w / w), about 0.4%(w / w) to about 1.9%(w / w), about 0.4% (w / w) to about 1.8% (w / w), about 0.4% (w / w) to about 1.7% (w / w), about 0.4% (w / w) to about 1.6% (w / w), about 0.4% (w / w) to about 1.5% (w / w), about 0.4% (w / w) to about 1.4% (w / w), about 0.4% (w / w) Approximately 1.3% (w / w), approximately 0.4% (w / w) to approximately 1.2% (w / w), approximately 0.4% (w / w) to approximately 1.1% (w / w), approximately 0.4% (w / w) to approximately 1% (w / w), approximately 0.4% (w / w) to approximately 0.9% (w / w), approximately 0.4% (w / w) to approximately 0.8% (w / w), approximately 0.4% ( (w / w) to about 0.7% (w / w), about 0.4% (w / w) to about 0.6% (w / w), about 0.4% (w / w) to about 0.5% (w / w), about 0.5% (w / w) to about 1.9% (w / w), about 0.5% (w / w) to about 1.8% (w / w), about 0.5% (w / w) to about 1.7% (w / w) , about 0.5% (w / w) to about 1.6% (w / w), about 0.5% (w / w) to about 1.5% (w / w), about 0.5% (w / w) to about 1.4% (w / w), about 0.5% (w / w) to about 1.3% (w / w), about 0.5% (w / w) to about 1.2% (w / w), about 0.5% (w / w) to about 1.1% (w / w), about 0.5% (w / w) to about 1% (w / w), about 0.5% (w / w) to about 0.9% (w / w), about 0.5% (w / w) to about 0.8% (w / w), about 0.5% (w / w) to about 0.7% (w / w), about 0.5% (w / w) to about 0.6% (w / w), about 0.6% (w / (w / w) to about 1.9% (w / w), about 0.6% (w / w) to about 1.8% (w / w), about 0.6% (w / w) to about 1.7% (w / w), about 0.6% (w / w) to about 1.6% (w / w), about 0.6% (w / w) to about 1.5% (w / w), about 0.6% (w / w) to about 1.4% (w / w), Approximately 0.6% (w / w) to approximately 1.3% (w / w), approximately 0.6% (w / w) to approximately 1.2% (w / w), approximately 0.6% (w / w) to approximately 1.1% (w / w), approximately 0.6% (w / w) to approximately 1% (w / w), approximately 0.6% (w / w) to approximately 0.9% (w / w), approximately 0.6% (w / w) to approximately 0.8% (w / w), about 0.6% (w / w) to about 0.7% (w / w), about 0.7% (w / w) to about 1.9% (w / w), about 0.7% (w / w) to about 1.8% (w / w), about 0.7% (w / w) to about 1.7% (w / w), about 0.7% (w / w) to about 1.6% (w / w), about 0.7% (w / (w / w) to about 1.5% (w / w), about 0.7% (w / w) to about 1.4% (w / w), about 0.7% (w / w) to about 1.3% (w / w), about 0.7% (w / w) to about 1.2% (w / w), about 0.7% (w / w) to about 1.1% (w / w), about 0.7% (w / w) to about 1% (w / w), about 0 0.7% (w / w) to approximately 0.9% (w / w), approximately 0.7% (w / w) to approximately 0.8% (w / w), approximately 0.8% (w / w) to approximately 1.9% (w / w), approximately 0.8% (w / w) to approximately 1.8% (w / w), approximately 0.8% (w / w) to approximately 1.7% (w / w), approximately 0.8% (w / w) to approximately 1.6% (w / w), about 0.8% (w / w) to about 1.5% (w / w), about 0.8% (w / w) to about 1.4% (w / w), about 0.8% (w / w) to about 1.3% (w / w), about 0.8% (w / w) to about 1.2% (w / w), about 0.8% (w / w) to about 1.1% (w / w), about 0.8% (w / (w / w) to about 1% (w / w), about 0.8% (w / w) to about 0.9% (w / w), about 0.9% (w / w) to about 1.9% (w / w), about 0.9% (w / w) to about 1.8% (w / w), about 0.9% (w / w) to about 1.7% (w / w), about 0.9% (w / w) to about 1.6% (w / w), about 0.9% (w / w) to approximately 1.5% (w / w), approximately 0.9% (w / w) to approximately 1.4% (w / w), approximately 0.9% (w / w) to approximately 1.3% (w / w), approximately 0.9% (w / w) to approximately 1.2% (w / w), approximately 0.9% (w / w) to approximately 1.1% (w / w), approximately 0.9% (w / w) to approximately 1% (w / w), about 1% (w / w) to about 1.9% (w / w), about 1% (w / w) to about 1.8% (w / w), about 1% (w / w) to about 1.7% (w / w), about 1% (w / w) to about 1.6% (w / w), about 1% (w / w) to about 1.5% (w / w), about 1% (w / w) to about 1.4% (w / w), about 1% (w / w) to approximately 1.3% (w / w), approximately 1% (w / w) to approximately 1.2% (w / w), approximately 1% (w / w) to approximately 1.1% (w / w), approximately 1.1% (w / w) to approximately 1.9% (w / w), approximately 1.1% (w / w) to approximately 1.8% (w / w), approximately 1.1% (w / w) to approximately 1.7% (w / w) , about 1.1% (w / w) to about 1.6% (w / w), about 1.1% (w / w) to about 1.5% (w / w), about 1.1% (w / w) to about 1.4% (w / w), about 1.1% (w / w) to about 1.3% (w / w), about 1.1% (w / w) to about 1.2% (w / w), about 1.2% (w / w) to about 1 0.9% (w / w), approximately 1.2% (w / w) to approximately 1.8% (w / w), approximately 1.2% (w / w) to approximately 1.7% (w / w), approximately 1.2% (w / w) to approximately 1.6% (w / w), approximately 1.2% (w / w) to approximately 1.5% (w / w), approximately 1.2% (w / w) to approximately 1.4% (w / w), approximately 1.2% (w / w) to about 1.3% (w / w), about 1.3% (w / w) to about 1.9% (w / w), about 1.3% (w / w) to about 1.8% (w / w), about 1.3% (w / w) to about 1.7% (w / w), about 1.3% (w / w) to about 1.6% (w / w), about 1.3% (w / w) to about 1.5% (w / w), about 1.3% (w / w) to about 1.4% (w / w), about 1.4% (w / w) to about 1.9% (w / w), about 1.4% (w / w) to about 1.8% (w / w), about 1.4% (w / w) to about 1.7% (w / w), about 1.4% (w / w) to about 1.6% (w / w), about 1.4% (w / w) Approximately 1.5% (w / w), approximately 1.5% (w / w) to approximately 1.9% (w / w), approximately 1.5% (w / w) to approximately 1.8% (w / w), approximately 1.5% (w / w) to approximately 1.7% (w / w), approximately 1.5% (w / w) to approximately 1.6% (w / w), approximately 1.6% (w / w) to approximately 1.9% (w / w), approximately 1.The concentration may be 6% (w / w) to about 1.8% (w / w), about 1.6% (w / w) to about 1.7% (w / w), about 1.7% (w / w) to about 1.9% (w / w), about 1.7% (w / w) to about 1.8% (w / w), or about 1.8% (w / w) to about 1.9% (w / w), in certain embodiments, in the liquid pharmaceutical formulations described herein. The amount of sodium disulfite in the liquid pharmaceutical formulations described herein can be from about 0.01% (w / w) to about 0.3% (w / w). In certain embodiments, the amount of sodium disulfite in the liquid pharmaceutical formulations described herein can be from about 0.05% (w / w) to about 2% (w / w).

[0084] In certain embodiments, the amount of sodium disulfite in the liquid pharmaceutical formulations described herein is about 0.05% (w / w), about 0.1% (w / w), about 0.2% (w / w), about 0.3% (w / w), about 0.4% (w / w), about 0.5% (w / w), about 0.6% (w / w), about 0.7% (w / w), about 0.8% (w / w), or about 0.1% (w / w). ), about 0.9% (w / w), about 1.0% (w / w), about 1.1% (w / w), about 1.2% (w / w), about 1.3% (w / w), about 1.4% (w / w), about 1.5% (w / w), about 1.6% (w / w), about 1.7% (w / w), about 1.8% (w / w), about 1.9% (w / w), or about 2.0% (w / w). In certain embodiments, the amount of antioxidant in the liquid pharmaceutical formulations described herein may be about 0.3% (w / w).

[0085] Osmolality and osmolality In certain embodiments, the liquid pharmaceutical formulations described herein provide a saturation level of about 100 mOsm / kg to about 1600 mOsm / kg, about 200 mOsm / kg to about 1600 mOsm / kg, about 300 mOsm / kg to about 1600 mOsm / kg, about 400 mOsm / kg to about 1600 mOsm / kg, about 600 mOsm / kg to about 1600 mOsm / kg, about 800 mOsm / kg to about 1600 mOsm / kg, about 120 mOsm / kg to about 1600 mOsm / kg, about 180 mOsm / kg to about 1600 mOsm / kg, about 200 mOsm / kg to about 1600 mOsm / kg, about 250 mOsm / kg to about 1600 mOsm / kg, about 300 mOsm / kg to about 1600 mOsm / kg, about 400 mOsm / kg to about 1600 mOsm / kg, about 600 mOsm / kg to about 1600 mOsm / kg, about 800 mOsm / kg to about 1600 mOsm / kg, about 120 mOsm / kg to about 1600 mOsm / kg, about 18 ... 0mOsm / kg~about 1600mOsm / kg, about 100mOsm / kg~about 1200mOsm / kg, about 100mOsm / kg~about 800mOsm / kg, about 100mOsm / kg~about 600mOsm / kg, about 100mOsm / kg to about 400mOsm / kg, about 100mOsm / kg to about 300mOsm / kg, about 100mOsm / kg to about 200mOsm / kg, about 200mOsm / kg to about 1200 mOsm / kg, about 200mOsm / kg~about 800mOsm / kg, about 200mOsm / kg~about 600mOsm / kg, about 200mOsm / kg~about 400mOsm / kg, about 200mOsm / kg~ Approx. 300mOsm / kg, Approx. 300mOsm / kg~Approx. 1200mOsm / kg, Approx. 300mOsm / kg~Approx. 800mOsm / kg, Approx. 300mOsm / kg~Approx. 600mOsm / kg, Approx. 300mOs In some embodiments, the liquid pharmaceutical formulations described herein have an osmolality in the range of about 200 mOsm / kg to about 400 mOsm / kg. In some embodiments, the liquid pharmaceutical formulations described herein have an osmolality in the range of about 300 mOsm / kg to about 600 mOsm / kg. In some embodiments, the liquid pharmaceutical formulations described herein have an osmolality in the range of about 300 mOsm / kg to about 600 mOsm / kg. In some embodiments, the liquid pharmaceutical formulations described herein have an osmolality in the range of about 300 mOsm / kg to about 600 mOsm / kg. In some embodiments, the liquid pharmaceutical formulations described herein have an osmolality in the range of about 300 mOsm / kg to about 600 mOsm / kg. In some embodiments, the liquid pharmaceutical formulations described herein have an osmolality in the range of about 200 mOsm / kg to about 4 ...200 mOsm / kg to about 400 mOsm / kg. In some embodiments, the liquid pharmaceutical formulations described herein have an osmol In certain embodiments, the liquid pharmaceutical formulations described herein have an osmolality ranging from about 300 mOsm / kg to about 450 mOsm / kg.

[0086] In certain embodiments, the liquid pharmaceutical formulations described herein have an osmolality ranging from about 100 mOsm / kg to about 1600 mOsm / kg. In certain embodiments, the liquid pharmaceutical formulations described herein have an osmolality ranging from about 200 mOsm / kg to about 800 mOsm / kg. In certain embodiments, the liquid pharmaceutical formulations described herein have an osmolality ranging from about 200 mOsm / kg to about 600 mOsm / kg. In certain embodiments, the liquid pharmaceutical formulations described herein have an osmolality ranging from about 200 mOsm / kg to about 400 mOsm / kg. In certain embodiments, the liquid pharmaceutical formulations described herein have an osmolality ranging from about 275 mOsm / kg to about 400 mOsm / kg.

[0087] It should be understood that the above ranges and explanations for osmolality are equally applicable to osmolality, but using the units "Osm / kg."

[0088] In certain embodiments, the liquid pharmaceutical formulations described herein may further comprise an osmolality or osmolality adjuster.

[0089] In certain embodiments, the osmolality or osmolality adjuster is selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof. In certain embodiments, the osmolality or osmolality adjuster is sodium chloride, potassium chloride, or a combination thereof. In certain embodiments, the osmolality or osmolality adjuster is sodium chloride. In certain embodiments, the osmolality or osmolality adjuster is potassium chloride.

[0090] Other pharmaceutically acceptable excipients In certain embodiments, the liquid pharmaceutical formulations described herein can further comprise one or more additional pharmaceutically acceptable excipients (e.g., solubilizing agents, pharmaceutically acceptable carriers, etc.).

[0091] In certain embodiments, the amount of one or more additional pharmaceutically acceptable excipients in the liquid pharmaceutical formulations described herein is from about 0.1% (w / w) to about 30% (w / w), from about 0.5% (w / w) to about 30% (w / w), from about 1% (w / w) to about 30% (w / w), from about 1.5% (w / w) to about 30% (w / w), (w / w), from about 2% (w / w) to about 30% (w / w), from about 2.5% (w / w) to about 30% (w / w), from about 3% (w / w) to about 30% (w / w), from about 3.5% (w / w) to about 30% (w / w), about 4% (w / w), or / w) to about 30% (w / w), about 4.5% (w / w) to about 30% (w / w), about 5% (w / w) to about 30% (w / w), about 10% (w / w) to about 30% (w / w), about 15% (w / w) to about 30% (w / w), about 20% (w / w) to about 30% (w / w), about 25% (w / w) to about 30% (w / w), about 0.1% (w / w) to about 25% (w / w), about 0.1% (w / w) to about 20% (w / w), about 0.1% (w / w) to about 15% (w / w), about 0.1% (w / w) to about 10% (w / w), about 0.1% (w / w) ~ about 5% (w / w), about 0.1% (w / w) to about 4.5% (w / w), about 0.1% (w / w) to about 4% (w / w), about 0.1% (w / w) to about 3.5% (w / w), about 0.1% (w / w) to about 3% (w / w), about 0.1% (w / w) to about 2.5% (w / w), about 0.1% (w / w) to about 2% (w / w), about 0.1% (w / w) to about 1.5% (w / w), about 0.1% (w / w) to about 1% (w / w), about 0.1% (w / w) to about 0.5% (w / w), about 0.5% (w / w) to about 25% (w / w), about 0.5% ( (w / w) to about 20% (w / w), about 0.5% (w / w) to about 15% (w / w), about 0.5% (w / w) to about 10% (w / w), about 0.5% (w / w) to about 5% (w / w), about 0.5% (w / w) to about 4.5% (w / w), about 0.5% (w / w) to about 4% (w / w), about 0.5% (w / w) to about 3.5% (w / w), about 0.5% (w / w) to about 3% (w / w), about 0.5% (w / w) to about 2.5% (w / w), about 0.5% (w / w) to about 2% (w / w), about 0.5% (w / w) to about 1.5% (w / w), about 0.5% (w / w) to approximately 1% (w / w), approximately 1% (w / w) to approximately 25% (w / w), approximately 1% (w / w) to approximately 20% (w / w), approximately 1% (w / w) to approximately 15% (w / w), approximately 1% (w / w) to approximately 10% (w / w), approximately 1% (w / w) to approximately 5% (w / w), approximately 1% (w / w) to approximately 4. 5% (w / w), approximately 1% (w / w) to approximately 4% (w / w), approximately 1% (w / w) to approximately 3.5% (w / w), approximately 1% (w / w) to approximately 2.5% (w / w), approximately 1% (w / w) to approximately 2% (w / w), approximately 1% (w / w) to approximately 1.5% (w / w), approximately 1.5% (w / w) to approximately 25% (w / w) , about 1.5% (w / w) to about 20% (w / w), about 1.5% (w / w) to about 15% (w / w), about 1.5% (w / w) to about 10% (w / w), about 1.5% (w / w) to about 5% (w / w), about 1.5% (w / w) to about 4.5% (w / w), about 1.5% (w / w) to about 4% (w / w) ), about 1.5% (w / w) to about 3.5% (w / w), about 1.5% (w / w) to about 3% (w / w), about 1.5% (w / w) to about 2.5% (w / w), about 1.5% (w / w) to about 2% (w / w), about 2% (w / w) to about 25% (w / w), about 2% (w / w) to about 20% (w / w), Approximately 2% (w / w) to approximately 15% (w / w), approximately 2% (w / w) to approximately 10% (w / w), approximately 2% (w / w) to approximately 5% (w / w), approximately 2% (w / w) to approximately 4.5% (w / w), approximately 2% (w / w) to approximately 4% (w / w), approximately 2% (w / w) to approximately 3.5% (w / w), approximately 2% (w / w) to Approximately 3% (w / w), approximately 2% (w / w) to approximately 2.5% (w / w), approximately 2.5% (w / w) to approximately 25% (w / w), approximately 2.5% (w / w) to approximately 20% (w / w), approximately 2.5% (w / w) to approximately 15% (w / w), approximately 2.5% (w / w) to approximately 10% (w / w), approximately 2.5% (w / w) Approximately 5% (w / w), approximately 2.5% (w / w) to approximately 4.5% (w / w), approximately 2.5% (w / w) to approximately 4% (w / w), approximately 2.5% (w / w) to approximately 3.5% (w / w), approximately 2.5% (w / w) to approximately 3% (w / w), approximately 3% (w / w) to approximately 25% (w / w), approximately 3% (w / w) to approximately 20 % (w / w), about 3% (w / w) to about 15% (w / w), about 3% (w / w) to about 10% (w / w), about 3% (w / w) to about 5% (w / w), about 3% (w / w) to about 4.5% (w / w), about 3% (w / w) to about 4% (w / w), about 3% (w / w) to about 3.5% (w / w), about 3.5% (w / w) to about 25% (w / w), about 3.5% (w / w) to about 20% (w / w), about 3.5% (w / w) to about 15% (w / w), about 3.5% (w / w) to about 10% (w / w), about 3.5% (w / w) to about 5% (w / w), about 3.5% (w / w) to about 4.5% (w / w), about 3.5% (w / w) to about 4% (w / w) ), about 4% (w / w) to about 25% (w / w), about 4% (w / w) to about 20% (w / w), about 4% (w / w) to about 15% (w / w), about 4% (w / w) to about 10% (w / w), about 4% (w / w) to about 5% (w / w), about 4% (w / w) to about 4.5% (w / w), about 4.5% (w / w) to about 25% (w / w), about 4.5 %(w / w) to about 20%(w / w), about 4.5%(w / w) to about 15%(w / w), about 4.5%(w / w) to about 10%(w / w), about 4.5%(w / w) to about 5%(w / w), about 5%(w / w) to about 25%(w / w), about 5%(w / w) to about 20%(w / w), about 5%(w / w) to about 15%(w / w), about 5%(w The concentration may be from about 10% (w / w) to about 10% (w / w), from about 10% (w / w) to about 25% (w / w), from about 10% (w / w) to about 20% (w / w), from about 10% (w / w) to about 15% (w / w), from about 15% (w / w) to about 25% (w / w), from about 15% (w / w) to about 20% (w / w), or from about 20% (w / w) to about 25% (w / w).

[0092] In certain embodiments, the amount of one or more additional pharmaceutically acceptable excipients in the liquid pharmaceutical formulations described herein is about 0.1% (w / w), about 0.25% (w / w), about 0.5% (w / w), about 0.75% (w / w), about 1% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3% (w / w), about 3.5% (w / w), about 4% (w / w), about 4.5% (w / w), about 5% (w / w), about 6% (w / w), , about 7% (w / w), about 8% (w / w), about 9% (w / w), about 10% (w / w), about 11% (w / w), about 12% (w / w), about 13% (w / w), about 14% (w / w), about 15% (w / w), about 16% (w / w), about 17% (w / w), about 18% (w / w), about 19% (w / w), about 20% (w / w), about 21% (w / w), about 22% (w / w), about 23% (w / w), about 24% (w / w), about 25% (w / w), about 26% (w / w), about 27% (w / w), about 28% (w / w), about 29% (w / w), or about 30% (w / w). In certain embodiments, the amount of one or more additional pharmaceutically acceptable excipients in the liquid pharmaceutical formulations described herein may be about 1% (w / w). In certain embodiments, the amount of one or more additional pharmaceutically acceptable excipients in the liquid pharmaceutical formulations described herein may be about 3.5% (w / w).

[0093] In certain embodiments, the one or more additional pharmaceutically acceptable excipients are selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0094] In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise ethanol. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise benzyl alcohol. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise glycerin. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise N-methyl-pyrrolidone (NMP). In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise sodium chloride. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise sodium carbonate. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise mannitol. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise lactose. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise dextrose. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise polyethylene glycol (PEG). In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise propylene glycol. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise a polysorbate (e.g., polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate). In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise polyvinylpyrrolidone (PVP). In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise a cyclodextrin. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise a cyclodextrin derivative. In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise vitamin E.In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise one or more naturally occurring forms of vitamin E (e.g., alpha-tocopherol, beta-tocopherol, gamma-tocopherol, and delta-tocopherol and alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, and delta-tocotrienol). In certain embodiments, the one or more additional pharmaceutically acceptable excipients comprise a vitamin E derivative (e.g., tocopheryl acetate, tocopheryl glucoside, tocopheryl phosphate).

[0095] (1) Benzyl alcohol In certain embodiments, the liquid pharmaceutical formulations described herein may further comprise benzyl alcohol. In certain embodiments, the benzyl alcohol in the liquid pharmaceutical formulations described herein may act as a solubilizing agent.

[0096] In certain embodiments, the amount of benzyl alcohol in the liquid pharmaceutical formulations described herein is from about 0.1% (w / w) to about 10% (w / w), from about 0.5% (w / w) to about 10% (w / w), from about 1% (w / w) to about 10% (w / w), from about 1.5% (w / w) to about 10% (w / w), from about 2% (w / w) to about 10% (w / w), from about 2.5% (w / w) to about 10% (w / w), from about 3% (w / w) to about 10% (w / w), from about 3.5% (w / w) to about 10% (w / w), from about 4% (w / w) to about 10% (w / w), from about 4.5% (w / w) to about 10% (w / w), About 5% (w / w) to about 10% (w / w), about 6% (w / w) to about 10% (w / w), about 7% (w / w) to about 10% (w / w), about 8% (w / w) to about 10% (w / w), about 9% (w / w) to about 10% (w / w), about 0.1% (w / w) to about 9% (w / w), about 0.1% (w / w) to about 8% (w / w), about 0.1% (w / w) to about 7% (w / w), about 0.1% (w / w) to about 6% (w / w), about 0.1% (w / w) to about 4.5% (w / w), about 0.1% (w / w) to about 4% (w / w), about 0.1% (w / w) to about 3.5% (w / w), about 0.1% ( (w / w) to about 3% (w / w), about 0.1% (w / w) to about 2.5% (w / w), about 0.1% (w / w) to about 2% (w / w), about 0.1% (w / w) to about 1.5% (w / w), about 0.1% (w / w) to about 1% (w / w), about 0.1% (w / w) to about 0.5% (w / w), about 0.5% (w / w) to about 9% (w / w), about 0.5% (w / w) to about 8% (w / w), about 0.5% (w / w) to about 7% (w / w), about 0.5% (w / w) to about 6% (w / w), about 0.5% (w / w) to about 5% (w / w), about 0.5% (w / w) to about 4.5% (w / w), about 0. 5% (w / w) to approximately 4% (w / w), approximately 0.5% (w / w) to approximately 3.5% (w / w), approximately 0.5% (w / w) to approximately 3% (w / w), approximately 0.5% (w / w) to approximately 2.5% (w / w), approximately 0.5% (w / w) to approximately 2% (w / w), approximately 0.5% (w / w) to approximately 1.5% (w / w) , about 0.5% (w / w) to about 1% (w / w), about 1% (w / w) to about 9% (w / w), about 1% (w / w) to about 8% (w / w), about 1% (w / w) to about 7% (w / w), about 1% (w / w) to about 6% (w / w), about 1% (w / w) to about 5% (w / w), about 1% (w / w) to about 4.5% (w / w), about 1% (w / w) to about 4% (w / w), about 1% (w / w) to about 3.5% (w / w), about 1% (w / w) to about 3% (w / w), about 1% (w / w) to about 2.5% (w / w), about 1% (w / w) to about 2% (w / w), about 1% (w / w) to about 1.5% (w / w), about 1.5% (w / w) to approximately 9% (w / w), approximately 1.5% (w / w) to approximately 8% (w / w), approximately 1.5% (w / w) to approximately 7% (w / w), approximately 1.5% (w / w) to approximately 6% (w / w), approximately 1.5% (w / w) to approximately 5% (w / w), approximately 1.5% (w / w) to approximately 4.5% (w / w), approximately 1. 5% (w / w) to about 4% (w / w), about 1.5% (w / w) to about 3.5% (w / w), about 1.5% (w / w) to about 3% (w / w), about 1.5% (w / w) to about 2.5% (w / w), about 1.5% (w / w) to about 2% (w / w), about 2% (w / w) to about 9% (w / w), about 2% (w / w) to about 8% (w / w), about 2% (w / w) to about 7% (w / w), about 2% (w / w) to about 6% (w / w), about 2% (w / w) to about 5% (w / w), about 2% (w / w) to about 4.5% (w / w), about 2% (w / w) to about 4% (w / w), about 2% (w / w) to about 3.5% (w / w) , about 2% (w / w) to about 3% (w / w), about 2% (w / w) to about 2.5% (w / w), about 2.5% (w / w) to about 9% (w / w), about 2.5% (w / w) to about 8% (w / w), about 2.5% (w / w) to about 7% (w / w), about 2.5% (w / w) to about 6% (w / w), about 2.5% (w / w) to about 5% (w / w), about 2.5% (w / w) to about 4.5% (w / w), about 2.5% (w / w) to about 4% (w / w), about 2.5% (w / w) to about 3.5% (w / w), about 2.5% (w / w) to about 3% (w / w), about 3% (w / w) to about 9% (w / w), about 3% (w / w) ) to about 8% (w / w), about 3% (w / w) to about 7% (w / w), about 3% (w / w) to about 6% (w / w), about 3% (w / w) to about 5% (w / w), about 3% (w / w) to about 4.5% (w / w), about 3% (w / w) to about 4% (w / w), about 3% (w / w) to about 3.5% (w / w), about 3.5% (w / w) to approximately 9% (w / w), approximately 3.5% (w / w) to approximately 8% (w / w), approximately 3.5% (w / w) to approximately 7% (w / w), approximately 3.5% (w / w) to approximately 6% (w / w), approximately 3.5% (w / w) to approximately 5% (w / w), approximately 3.5% (w / w) to approximately 4.5% (w / w), approximately 3.5% (w / w) to about 4% (w / w), about 4% (w / w) to about 9% (w / w), about 4% (w / w) to about 8% (w / w), about 4% (w / w) to about 7% (w / w), about 4% (w / w) to about 6% (w / w), about 4% (w / w) to about 5% (w / w), about 4% (w / w) to about 4.5% (w / w), about 4.5% (w / w) to about 9% (w / w), about 4.5% (w / w) to about 8% (w / w), about 4.5% (w / w) to about 7% (w / w), about 4.5% (w / w) to about 6% (w / w), The amount of benzyl alcohol in the liquid pharmaceutical formulations described herein can be about 4.5% (w / w) to about 5% (w / w), about 5% (w / w) to about 9% (w / w), about 5% (w / w) to about 8% (w / w), about 5% (w / w) to about 7% (w / w), about 5% (w / w) to about 6% (w / w), about 6% (w / w) to about 9% (w / w), about 6% (w / w) to about 8% (w / w), about 6% (w / w) to about 7% (w / w), about 7% (w / w) to about 9% (w / w), about 7% (w / w) to about 8% (w / w), or about 8% (w / w) to about 9% (w / w). In certain embodiments, the amount of benzyl alcohol in the liquid pharmaceutical formulations described herein is about 0.1% (w / w) to about 10% (w / w). In certain embodiments, the amount of benzyl alcohol in the liquid pharmaceutical formulations described herein is from about 1% (w / w) to about 3.5% (w / w).

[0097] In certain embodiments, the amount of benzyl alcohol in the liquid pharmaceutical formulations described herein can be about 0.1% (w / w), about 0.5% (w / w), about 1% (w / w), about 1.5% (w / w), about 2% (w / w), about 2.5% (w / w), about 3% (w / w), about 3.5% (w / w), about 4% (w / w), about 4.5% (w / w), about 5% (w / w), about 6% (w / w), about 7% (w / w), about 8% (w / w), about 9% (w / w), or about 10% (w / w). In certain embodiments, the amount of benzyl alcohol in the liquid pharmaceutical formulations described herein can be about 1% (w / w). In certain embodiments, the amount of benzyl alcohol in the liquid pharmaceutical formulations described herein can be about 3.5% (w / w).

[0098] (2) Cyclodextrin and derivatives In certain embodiments, the liquid pharmaceutical formulations described herein may include a cyclodextrin. In certain embodiments, the liquid pharmaceutical formulations described herein may include a cyclodextrin derivative.

[0099] Cyclodextrins contemplated as useful pharmaceutically acceptable excipients include, but are not limited to, α (alpha)-cyclodextrin, β (beta)-cyclodextrin, and γ (gamma)-cyclodextrin. In certain embodiments, the liquid pharmaceutical formulations described herein may include α-cyclodextrin. In certain embodiments, the liquid pharmaceutical formulations described herein may include β-cyclodextrin. In certain embodiments, the liquid pharmaceutical formulations described herein may include γ-cyclodextrin.

[0100] Cyclodextrin derivatives contemplated to be useful as pharmaceutically acceptable excipients include, but are not limited to, sulfobutyl-ether-β-cyclodextrin (e.g., Captisol), hydroxypropyl-β-cyclodextrin (e.g., 2-hydroxypropyl-β-cyclodextrin), and methylated β-cyclodextrin (e.g., randomly methylated β-cyclodextrin). In certain embodiments, the liquid pharmaceutical formulations described herein may include sulfobutyl-ether-β-cyclodextrin. In certain embodiments, the liquid pharmaceutical formulations described herein may include Captisol®. In certain embodiments, the liquid pharmaceutical formulations described herein may include hydroxypropyl-β-cyclodextrin. In certain embodiments, the liquid pharmaceutical formulations described herein may include methylated β-cyclodextrin.

[0101] In certain embodiments, the amount of cyclodextrin in the liquid pharmaceutical formulation is from about 5% to about 50% (w / w), from about 10% to about 50% (w / w), from about 15% to about 50% (w / w), from about 20% to about 50% (w / w), from about 20% to about 50% (w / w), from about 25% to about 50% (w / w), from about 30% to about 50% (w / w), from about 35% to about 50% (w / w), from about 40% to about 50% (w / w), or from about 45% to about 50% (w / w). ), about 5% to about 45% (w / w), about 5% to about 40% (w / w), about 5% to about 35% (w / w), about 5% to about 30% (w / w), about 5% to about 25% (w / w), about 5% to about 20% (w / w), about 5% to about 15% (w / w), about 5% to about 10% (w / w), about 10% to about 45% (w / w), about 10% to about 40% (w / w), about 10% to about 35% (w / w), about 10% to about 30% (w / w), about 10% to about 25% (w / w), about 10% to about 20% (w / w), about 10% to about 15% (w / w), about 15% to about 45% (w / w), about 15% to about 40% (w / w), about 15% to about 35% (w / w), about 15% to about 30% (w / w), about 15% to about 25% (w / w), about 15% to about 20% (w / w), about 20% to about 45% (w / w), about 20% to about 40% (w / w), about 20% to about 35% (w / w), about 20% to about 30% (w / w), about 20% to about 25% (w / w), about 25% to about 45% (w / w), about 25% to about 40% (w / w), about 25% to about 35% (w / w), about 25% to about 30% (w / w), about 30% to about 45% (w / w), about 30% to about 40% (w / w), about 30% to about 35% (w / w), about 35% to about 45% (w / w), about 35% to about 40% (w / w), or about 40% to about 45% (w / w).

[0102] In certain embodiments, the amount of cyclodextrin derivative in the liquid pharmaceutical formulation is about 5% to about 50% (w / w), about 10% to about 50% (w / w), about 15% to about 50% (w / w), about 20% to about 50% (w / w), about 20% to about 50% (w / w), about 25% to about 50% (w / w), about 30% to about 50% (w / w), about 35% to about 50% (w / w), about 40% to about 50% (w / w), or about 45% to about 50% (w / w). / w), about 5% to about 45% (w / w), about 5% to about 40% (w / w), about 5% to about 35% (w / w), about 5% to about 30% (w / w), about 5% to about 25% (w / w), about 5% to about 20% (w / w), about 5% to about 15% (w / w), about 5% to about 10% (w / w), about 10% to about 45% (w / w), about 10% to about 40% (w / w), about 10% to about 35% (w / w), about 10% to about 30% (w / w), about 10% to About 25% (w / w), about 10% to about 20% (w / w), about 10% to about 15% (w / w), about 15% to about 45% (w / w), about 15% to about 40% (w / w), about 15% to about 35% (w / w), about 15% to about 30% (w / w), about 15% to about 25% (w / w), about 15% to about 20% (w / w), about 20% to about 45% (w / w), about 20% to about 40% (w / w), about 20% to about 35% (w / w), about 20% to about 30% (w / w), about 20% to about 25% (w / w), about 25% to about 45% (w / w), about 25% to about 40% (w / w), about 25% to about 35% (w / w), about 25% to about 30% (w / w), about 30% to about 45% (w / w), about 30% to about 40% (w / w), about 30% to about 35% (w / w), about 35% to about 45% (w / w), about 35% to about 40% (w / w), or about 40% to about 45% (w / w).

[0103] In certain embodiments, the amount of cyclodextrin in the liquid pharmaceutical formulation is 5% (w / w) or less, 10% (w / w) or less, 15% (w / w) or less, 20% (w / w) or less, 25% (w / w) or less, 30% (w / w) or less, 35% (w / w) or less, 40% (w / w) or less, 45% (w / w) or less, or 50% (w / w) or less.

[0104] In certain embodiments, the amount of cyclodextrin derivative in the liquid pharmaceutical formulation is 5% (w / w) or less, 10% (w / w) or less, 15% (w / w) or less, 20% (w / w) or less, 25% (w / w) or less, 30% (w / w) or less, 35% (w / w) or less, 40% (w / w) or less, 45% (w / w) or less, or 50% (w / w) or less.

[0105] In certain embodiments, the amount of cyclodextrin in the liquid pharmaceutical formulation is about 5% (w / w), about 6% (w / w), about 7% (w / w), about 8% (w / w), about 9% (w / w), about 10% (w / w), about 11% (w / w), about 12% (w / w), about 13% (w / w), about 14% (w / w), about 15% (w / w), about 16% (w / w), about 17% (w / w), about 18% (w / w), about 19% (w / w), about 20% (w / w), about 25% (w / w), about 30% (w / w), about 35% (w / w), about 40% (w / w), about 45% (w / w), or about 50% (w / w).

[0106] In certain embodiments, the amount of cyclodextrin derivative in the liquid pharmaceutical formulation is about 5% (w / w), about 6% (w / w), about 7% (w / w), about 8% (w / w), about 9% (w / w), about 10% (w / w), about 11% (w / w), about 12% (w / w), about 13% (w / w), about 14% (w / w), about 15% (w / w), about 16% (w / w), about 17% (w / w), about 18% (w / w), about 19% (w / w), about 20% (w / w), about 25% (w / w), about 30% (w / w), about 35% (w / w), about 40% (w / w), about 45% (w / w), or about 50% (w / w).

[0107] In certain embodiments, the concentration of cyclodextrin in the liquid pharmaceutical formulation is from about 40 mM to about 200 mM, from about 50 mM to about 200 mM, from about 60 mM to about 200 mM, from about 70 mM to about 200 mM, from about 80 mM to about 200 mM, from about 90 mM to about 200 mM, from about 100 mM to about 200 mM, from about 120 mM to about 200 mM, from about 140 mM to about 200 mM, from about 160 mM to about 200 mM, from about 180 mM to about 200 mM, from about 40 mM to about 180 mM, from about 40 mM to about 160 mM, from about 40 mM to about 140 mM, or from about 40 mM to about 180 mM. M ~ about 120mM, about 40mM - about 100mM, about 40mM - about 90mM, about 40mM - about 80mM, about 40mM - about 70mM, about 40mM - about 60mM, about 40mM - about 50mM, about 50mM - about 180mM, about 50mM - about 160mM, about 50m M ~ about 140mM, about 50mM - about 120mM, about 50mM - about 100mM, about 50mM - about 90mM, about 50mM - about 80mM, about 50mM - about 70mM, about 50mM - about 60mM, about 60mM - about 180mM, about 60mM - about 160mM, about 60 mm~140mM, 60mM~120mM, 60mM~100mM, 60mM~90mM, 60mM~80mM, 60mM~70mM, 70mM~180mM, 70mM~160mM, 70mM~140mM, approx. 70mM to about 120mM, about 70mM to about 100mM, about 70mM to about 90mM, about 70mM to about 80mM, about 80mM to about 180mM, about 80mM to about 160mM, about 80mM to about 140mM, about 80mM to about 120mM, about 80mM to about 100m M, about 80mM to about 90mM, about 90mM to about 180mM, about 90mM to about 160mM, about 90mM to about 140mM, about 90mM to about 120mM, about 90mM to about 100mM, about 100mM to about 180mM, about 100mM to about 160mM, about 100m M ~ about 140mM, about 100mM - about 120mM, about 120mM - about 180mM, about 120mM - about 160mM, about 120mM - about 140mM, about 140mM - about 180mM, about 140mM - about 160mM, or about 160mM - about 180mM.

[0108] In certain embodiments, the concentration of the cyclodextrin derivative in the liquid pharmaceutical formulation is about 40 mM to about 200 mM, about 50 mM to about 200 mM, about 60 mM to about 200 mM, about 70 mM to about 200 mM, about 80 mM to about 200 mM, about 90 mM to about 200 mM, about 100 mM to about 200 mM, about 120 mM to about 200 mM, about 140 mM to about 200 mM, about 160 mM to about 200 mM, about 180 mM to about 200 mM, about 40 mM to about 180 mM, about 40 mM to about 160 mM, about 40 mM to about 140 mM, about 40 mM to about 140 mM, about 40 mM to about 180 mM, about 40 mM to about 160 mM, about 40 mM to about 140 mM, about 40 mM to about 140 mM, about 40 mM to about 16 ...60 mM, about 40 mM to about 140 mM, about 40 mM to about 160 mM, about 40 mM to about 160 mM, about 40 mM to about 160 mM, about 40 mM to about 160 mM, about 40 mM to about 160 mM, about 40 mM to about 160 mM, about 40 mM to about 160 mM, about 40 mM 0mM to about 120mM, about 40mM to about 100mM, about 40mM to about 90mM, about 40mM to about 80mM, about 40mM to about 70mM, about 40mM to about 60mM, about 40mM to about 50mM, about 50mM to about 180mM, about 50mM to about 160mM, about 5 0mM to about 140mM, about 50mM to about 120mM, about 50mM to about 100mM, about 50mM to about 90mM, about 50mM to about 80mM, about 50mM to about 70mM, about 50mM to about 60mM, about 60mM to about 180mM, about 60mM to about 160mM, about 6 0mM to about 140mM, about 60mM to about 120mM, about 60mM to about 100mM, about 60mM to about 90mM, about 60mM to about 80mM, about 60mM to about 70mM, about 70mM to about 180mM, about 70mM to about 160mM, about 70mM to about 140mM, Approximately 70mM to approximately 120mM, approximately 70mM to approximately 100mM, approximately 70mM to approximately 90mM, approximately 70mM to approximately 80mM, approximately 80mM to approximately 180mM, approximately 80mM to approximately 160mM, approximately 80mM to approximately 140mM, approximately 80mM to approximately 120mM, approximately 80mM to approximately 100m M, about 80mM to about 90mM, about 90mM to about 180mM, about 90mM to about 160mM, about 90mM to about 140mM, about 90mM to about 120mM, about 90mM to about 100mM, about 100mM to about 180mM, about 100mM to about 160mM, about 100m M ~ about 140mM, about 100mM - about 120mM, about 120mM - about 180mM, about 120mM - about 160mM, about 120mM - about 140mM, about 140mM - about 180mM, about 140mM - about 160mM, or about 160mM - about 180mM.

[0109] In certain embodiments, the concentration of cyclodextrin in the liquid pharmaceutical formulation is about 40 mM, about 45 mM, about 50 mM, about 55 mM, about 60 mM, about 65 mM, about 70 mM, about 75 mM, about 80 mM, about 85 mM, about 90 mM, about 95 mM, about 100 mM, about 110 mM, about 120 mM, about 130 mM, about 140 mM, about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, or about 200 mM.

[0110] In certain embodiments, the concentration of the cyclodextrin derivative in the liquid pharmaceutical formulation is about 40 mM, about 45 mM, about 50 mM, about 55 mM, about 60 mM, about 65 mM, about 70 mM, about 75 mM, about 80 mM, about 85 mM, about 90 mM, about 95 mM, about 100 mM, about 110 mM, about 120 mM, about 130 mM, about 140 mM, about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, or about 200 mM.

[0111] In certain embodiments, the liquid pharmaceutical formulation further comprises water (e.g., water for injection (WFI)).

[0112] Exemplary Furosemide Liquid Pharmaceutical Formulations In various embodiments, provided herein are liquid pharmaceutical formulations for treating a disease or disorder described herein (e.g., congestion, edema, fluid overload, or hypertension) in a patient in need thereof, comprising a therapeutically effective amount of furosemide and a pharmaceutically acceptable excipient. The liquid pharmaceutical formulation may include, inter alia, a pharmaceutically acceptable pH adjuster, antioxidant, osmolality adjuster, and / or a pharmaceutically acceptable buffer, as described herein.

[0113] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer.

[0114] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) tromethamine, or a pharmaceutically acceptable salt thereof.

[0115] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof.

[0116] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0117] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0118] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0119] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0120] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0121] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) pharmaceutically acceptable pH adjusters, including sodium hydroxide and hydrochloric acid.

[0122] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an antioxidant.

[0123] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0124] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant.

[0125] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0126] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0127] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0128] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0129] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0130] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0131] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) sodium chloride, including

[0132] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) one or more additional pharmaceutically acceptable excipients.

[0133] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0134] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0135] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer containing a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine, or a pharmaceutically acceptable salt thereof; and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0136] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0137] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof; and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0138] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) cyclodextrin or a derivative thereof.

[0139] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0140] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) Cyclodextrin or a derivative thereof.

[0141] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0142] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) Cyclodextrin or a derivative thereof.

[0143] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0144] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) benzyl alcohol.

[0145] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0146] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) benzyl alcohol, including

[0147] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0148] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) benzyl alcohol, including

[0149] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0150] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof; (iii) benzyl alcohol, (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0151] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof; (iii) about 0.1% (w / w) to about 10% (w / w) of benzyl alcohol; (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0152] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 1 mg / mL to about 250 mg / mL of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0153] Exemplary Bumetanide Liquid Pharmaceutical Formulations In various embodiments, provided herein are liquid pharmaceutical formulations for treating a disease or disorder described herein (e.g., congestion, edema, fluid overload, or hypertension) in a patient in need thereof, comprising a therapeutically effective amount of bumetanide and a pharmaceutically acceptable excipient. The liquid pharmaceutical formulation may include, inter alia, a pharmaceutically acceptable pH adjuster, antioxidant, osmolality adjuster, and / or a pharmaceutically acceptable buffer, as described herein.

[0154] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer.

[0155] In various embodiments, the liquid pharmaceutical formulation comprises: (i) bumetanide, or a pharmaceutically acceptable salt thereof, in a therapeutically effective amount; and (ii) tromethamine, or a pharmaceutically acceptable salt thereof.

[0156] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof.

[0157] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0158] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0159] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0160] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0161] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0162] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) pharmaceutically acceptable pH adjusters, including sodium hydroxide and hydrochloric acid.

[0163] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an antioxidant.

[0164] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0165] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant.

[0166] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0167] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0168] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0169] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0170] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0171] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0172] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) sodium chloride, including

[0173] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) one or more additional pharmaceutically acceptable excipients.

[0174] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0175] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0176] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer containing a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine, or a pharmaceutically acceptable salt thereof; and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0177] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0178] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof; and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0179] In various embodiments, the liquid pharmaceutical formulation comprises: (i) bumetanide, or a pharmaceutically acceptable salt thereof, in a therapeutically effective amount; and (ii) cyclodextrin or a derivative thereof.

[0180] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof, and (ii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0181] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) Cyclodextrin or a derivative thereof.

[0182] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0183] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) Cyclodextrin or a derivative thereof.

[0184] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0185] In various embodiments, the liquid pharmaceutical formulation comprises: (i) bumetanide, or a pharmaceutically acceptable salt thereof, in a therapeutically effective amount; and (ii) benzyl alcohol.

[0186] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof, and (ii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0187] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) benzyl alcohol, including

[0188] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0189] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) benzyl alcohol, including

[0190] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0191] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof; (iii) benzyl alcohol, (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0192] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof; (iii) about 0.1% (w / w) to about 10% (w / w) of benzyl alcohol; (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0193] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.025 mg / mL to about 65 mg / mL of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0194] Exemplary Torsemide Liquid Pharmaceutical Formulations In various embodiments, provided herein is a liquid pharmaceutical formulation for treating a disease or disorder described herein (e.g., congestion, edema, fluid overload, or hypertension) in a patient in need thereof, comprising a therapeutically effective amount of torsemide and a pharmaceutically acceptable excipient. The liquid pharmaceutical formulation may include, inter alia, a pharmaceutically acceptable pH adjuster, antioxidant, osmolality adjuster, and / or a pharmaceutically acceptable buffer, as described herein.

[0195] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer.

[0196] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) tromethamine, or a pharmaceutically acceptable salt thereof.

[0197] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof.

[0198] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0199] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0200] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0201] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0202] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0203] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) pharmaceutically acceptable pH adjusters, including sodium hydroxide and hydrochloric acid.

[0204] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an antioxidant.

[0205] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0206] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant.

[0207] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0208] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0209] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0210] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0211] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0212] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0213] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) sodium chloride, including

[0214] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) one or more additional pharmaceutically acceptable excipients.

[0215] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0216] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0217] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer containing a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine, or a pharmaceutically acceptable salt thereof; and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0218] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0219] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0220] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) cyclodextrin or a derivative thereof.

[0221] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0222] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) Cyclodextrin or a derivative thereof.

[0223] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0224] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) Cyclodextrin or a derivative thereof.

[0225] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0226] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) benzyl alcohol.

[0227] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0228] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) benzyl alcohol, including

[0229] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0230] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) benzyl alcohol, including

[0231] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0232] In various embodiments, the liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof; (iii) benzyl alcohol, (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0233] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof; (iii) about 0.1% (w / w) to about 10% (w / w) of benzyl alcohol; (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0234] In various embodiments, the liquid pharmaceutical formulation comprises: (i) about 0.5 mg / mL to about 125 mg / mL of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0235] Furosemide unit liquid pharmaceutical dosage form As described herein, in one aspect, the present invention provides a unit liquid pharmaceutical formulation of a loop diuretic (e.g., bumetanide, furosemide, or torsemide).

[0236] In various embodiments, the liquid pharmaceutical formulation generally comprises: (i) a therapeutically effective amount of a loop diuretic, or a pharmaceutically acceptable salt thereof; and (ii) pharmaceutically acceptable excipients, such as pharmaceutically acceptable pH adjusters, antioxidants, osmolality adjusters, and / or pharmaceutically acceptable buffers, as described herein.

[0237] Loop diuretics In certain embodiments, the amount of loop diuretic in the unit liquid pharmaceutical formulation described herein is from about 0.025 mg to about 250 mg, from about 0.1 mg to about 250 mg, from about 1 mg to about 250 mg, from about 5 mg to about 250 mg, from about 10 mg to about 250 mg, from about 20 mg to about 250 mg, from about 30 mg to about 250 mg, from about 40 mg to about 250 mg, from about 50 mg to about 250 mg, from about 60 mg to about 250 mg, from about 70 mg to about 250 mg, from about 80 mg to about 250 mg, from about 90 mg to about 250 mg, from about 100 mg to about 250 mg, from about 120 mg to about 250 mg, or from about 140 mg ~250mg, 160mg~250mg, 180mg~250mg, 200mg~250mg, 225mg~250mg, 0.025mg~225mg, 0.025mg~200mg, 0.025mg~180mg, 0.025mg~16 0mg, about 0.025mg to about 140mg, about 0.025mg to about 120mg, about 0.025mg to about 100mg, about 0.025mg to about 90mg, about 0.025mg to about 80mg, about 0.025mg to about 70mg, about 0.025mg to about 60mg, about 0.025mg to about 50 mg, approx. 0.025 mg ~ approx. 40 mg, approx. 0.025 mg ~ approx. 30 mg, approx. 0.025 mg ~ approx. 20 mg, approx. 0.025 mg ~ approx. 10 mg, approx. 0.025 mg ~ approx. 5 mg, approx. 1mg to about 200mg, about 0.1mg to about 180mg, about 0.1mg to about 160mg, about 0.1mg to about 140mg, about 0.1mg to about 120mg, about 0.1mg to about 100mg, about 0.1mg to about 90mg, about 0.1mg to about 80mg, about 0.1mg to about 70mg, about 0.1 mg~60mg, approx. 0.1mg~approx. 50mg, approx. 0.1mg~approx. 40mg, approx. 0.1mg~approx. 30mg, approx. 0.1mg~approx. 20mg, approx. mg~180mg, 1mg~160mg, 1mg~140mg, 1mg~120mg, 1mg~100mg, 1mg~90mg, 1mg~80mg, 1mg~70mg, 1mg~60mg, 1mg~50mg, 1mg~40mg,about 1 mg to about 30 mg, about 1 mg to about 20 mg, about 1 mg to about 10 mg, about 1 mg to about 5 mg, about 5 mg to about 225 mg, about 5 mg to about 200 mg, about 5 mg to about 180 mg, about 5 mg to about 160 mg, about 5 mg to about 140 mg, about 5 mg to about 120 mg, about 5 mg to about 100 mg, about 5 mg to about 90 mg, about 5 mg to about 80 mg, about 5 mg to about 70 mg, about 5 mg to about 60 mg, about 5 mg to about 50 mg, about 5 mg to about 40 mg, about 5 mg to about 30 mg, about 5 mg to about 20 mg, about 5 mg to about 10 mg, about 10 mg to about 225 mg, about 10 mg to about 20 0mg, about 10mg to about 180mg, about 10mg to about 160mg, about 10mg to about 140mg, about 10mg to about 120mg, about 10mg to about 100mg, about 10mg to about 90mg, about 10mg to about 80mg, about 10mg to about 70mg, about 10mg to about 60mg, about 10mg to about 50mg, about 10mg to about 40mg, about 10mg to about 30mg, about 10mg to about 20mg, about 20mg to about 225mg, about 20mg to about 200mg, about 20mg to about 180mg, about 20mg to about 160mg, about 20mg to about 140mg, about 20mg to about 120mg, about 20mg to about 100 mg, about 20 mg to about 90 mg, about 20 mg to about 80 mg, about 20 mg to about 70 mg, about 20 mg to about 60 mg, about 20 mg to about 50 mg, about 20 mg to about 40 mg, about 20 mg to about 30 mg, about 30 mg to about 225 mg, about 30 mg to about 200 mg, about 30 mg to about 180 mg, about 30 mg to about 160 mg, about 30 mg to about 140 mg, about 30 mg to about 120 mg, about 30 mg to about 100 mg, about 30 mg to about 90 mg, about 30 mg to about 80 mg, about 30 mg to about 70 mg, about 30 mg to about 60 mg, about 30 mg to about 50 mg, about 30 mg to about 40 mg, about 40 mg to about 225 mg, about 40 mg to about 200 mg, about 40 mg to about 180 mg, about 40 mg to about 160 mg, about 40 mg to about 140 mg, about 40 mg to about 120 mg, about 40 mg to about 100 mg, about 40 mg to about 90 mg, about 40 mg to about 80 mg, about 40 mg to about 70 mg, about 40 mg to about 60 mg, about 40 mg to about 50 mg, about 50 mg to about 225 mg, about 50 mg to about 200 mg, about 50 mg to about 180 mg, about 50 mg to about 160 mg, about 50 mg to about 140 mg, about 50 mg to about 120 mg, about 50 mg to about 100 mg,Approximately 50mg to approximately 90mg, approximately 50mg to approximately 80mg, approximately 50mg to approximately 70mg, approximately 50mg to approximately 60mg, approximately 60mg to approximately 225mg, approximately 60mg to approximately 200mg, approximately 60mg to approximately 180mg, approximately 60mg to approximately 160m g, about 60mg to about 140mg, about 60mg to about 120mg, about 60mg to about 100mg, about 60mg to about 90mg, about 60mg to about 80mg, about 60mg to about 70mg, about 70mg to about 225mg, about 70mg to about 2 00mg, about 70mg to about 180mg, about 70mg to about 160mg, about 70mg to about 140mg, about 70mg to about 120mg, about 70mg to about 100mg, about 70mg to about 90mg, about 70mg to about 80mg, about 70m g ~ about 225mg, about 80mg - about 200mg, about 80mg - about 180mg, about 80mg - about 160mg, about 80mg - about 140mg, about 80mg - about 120mg, about 80mg - about 100mg, about 80mg - about 90mg, Approximately 70mg to approximately 225mg, approximately 90mg to approximately 200mg, approximately 90mg to approximately 180mg, approximately 90mg to approximately 160mg, approximately 90mg to approximately 140mg, approximately 90mg to approximately 120mg, approximately 90mg to approximately 100mg, approximately 100mg to Approximately 225mg, approximately 100mg to approximately 200mg, approximately 100mg to approximately 180mg, approximately 100mg to approximately 160mg, approximately 100mg to approximately 140mg, approximately 100mg to approximately 120mg, approximately 120mg to approximately 225mg, approximately 120mg to The amount of loop diuretic in the unit liquid pharmaceutical formulation described herein can be about 200 mg, about 120 mg to about 180 mg, about 120 mg to about 160 mg, about 120 mg to about 140 mg, about 140 mg to about 225 mg, about 140 mg to about 200 mg, about 140 mg to about 180 mg, about 140 mg to about 160 mg, about 160 mg to about 225 mg, about 160 mg to about 200 mg, about 160 mg to about 180 mg, about 180 mg to about 225 mg, about 180 mg to about 200 mg, or about 200 mg to about 225 mg. In certain embodiments, the amount of loop diuretic in the unit liquid pharmaceutical formulation described herein can be about 0.025 mg to about 250 mg.

[0238] In certain embodiments, the amount of loop diuretic in the unit liquid pharmaceutical formulations described herein can be greater than about 0.025 mg, greater than about 0.1 mg, greater than about 1 mg, greater than about 5 mg, greater than about 10 mg, greater than about 20 mg, greater than about 30 mg, greater than about 40 mg, greater than about 50 mg, greater than about 60 mg, greater than about 70 mg, greater than about 80 mg, greater than about 90 mg, greater than about 100 mg, greater than about 110 mg, greater than about 120 mg, greater than about 130 mg, greater than about 140 mg, greater than about 150 mg, greater than about 160 mg, greater than about 170 mg, greater than about 180 mg, greater than about 190 mg, greater than about 200 mg, greater than about 210 mg, greater than about 220 mg, greater than about 230 mg, greater than about 240 mg, or greater than about 250 mg.

[0239] In certain embodiments, the amount of loop diuretic in the unit liquid pharmaceutical formulation described herein is about 0.025 mg, about 0.05 mg, about 0.075 mg, about 0.1 mg, about 0.2 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 22 mg, about 24 mg , about 26 mg, about 28 mg, about 30 mg, about 32 mg, about 34 mg, about 36 mg, about 38 mg, about 40 mg, about 42 mg, about 44 mg, about 46 mg, about 48 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, or about 250 mg.

[0240] In certain embodiments, the loop diuretic is selected from the group consisting of furosemide, bumetanide, ethacrynic acid, torsemide, or a pharmaceutically acceptable salt thereof. In certain embodiments, the loop diuretic is furosemide or a pharmaceutically acceptable salt thereof. In certain embodiments, the loop diuretic is bumetanide or a pharmaceutically acceptable salt thereof. In certain embodiments, the loop diuretic is ethacrynic acid or a pharmaceutically acceptable salt thereof. In certain embodiments, the loop diuretic is torsemide or a pharmaceutically acceptable salt thereof.

[0241] In certain embodiments, the amount of furosemide in the unit liquid pharmaceutical formulation described herein is from about 1 mg to about 250 mg, from about 5 mg to about 250 mg, from about 10 mg to about 250 mg, from about 20 mg to about 250 mg, from about 30 mg to about 250 mg, from about 40 mg to about 250 mg, from about 50 mg to about 250 mg, from about 60 mg to about 250 mg, from about 70 mg to about 250 mg, from about 80 mg to about 250 mg, from about 90 mg to about 250 mg, from about 100 mg to about 250 mg, from about 120 mg to about 250 mg, from about 140 mg to about 250 mg, from about 160 mg to about 250 mg, from about 180 mg to about 250 mg, 0mg, about 200mg to about 250mg, about 225mg to about 250mg, about 1mg to about 225mg, about 1mg to about 200mg, about 1mg to about 180mg, about 1mg to about 160mg, about 1mg to about 140mg, about 1mg to about 120mg, about 1mg to about 100mg, about 1mg to about 90 mg, about 1 mg to about 80 mg, about 1 mg to about 70 mg, about 1 mg to about 60 mg, about 1 mg to about 50 mg, about 1 mg to about 40 mg, about 1 mg to about 30 mg, about 1 mg to about 20 mg, about 1 mg to about 10 mg, about 1 mg to about 5 mg, about 5 mg to about 225 mg, about 5 mg to about 200 mg, About 5mg to about 180mg, about 5mg to about 160mg, about 5mg to about 140mg, about 5mg to about 120mg, about 5mg to about 100mg, about 5mg to about 90mg, about 5mg to about 80mg, about 5mg to about 70mg, about 5mg to about 60mg, about 5mg to about 50mg, about 5mg to about 40m g, approx. 5 mg ~ approx. 30 mg, approx. 5 mg ~ approx. 20 mg, approx. 5 mg ~ approx. 10 mg, approx. 10 mg ~ approx. 225 mg, approx. 10 mg ~ approx. 200 mg, approx. g, about 10mg to about 90mg, about 10mg to about 80mg, about 10mg to about 70mg, about 10mg to about 60mg, about 10mg to about 50mg, about 10mg to about 40mg, about 10mg to about 30mg, about 10mg to about 20mg, about 20mg to about 225mg, about 20mg to about 200mg, About 20mg to about 180mg, about 20mg to about 160mg, about 20mg to about 140mg, about 20mg to about 120mg, about 20mg to about 100mg, about 20mg to about 90mg, about 20mg to about 80mg, about 20mg to about 70mg, about 20mg to about 60mg, about 20mg to about 50mg,about 20 mg to about 40 mg, about 20 mg to about 30 mg, about 30 mg to about 225 mg, about 30 mg to about 200 mg, about 30 mg to about 180 mg, about 30 mg to about 160 mg, about 30 mg to about 140 mg, about 30 mg to about 120 mg, about 30 mg to about 100 mg, about 30 mg to about 90 mg, about 30 mg to about 80 mg, about 30 mg to about 70 mg, about 30 mg to about 60 mg, about 30 mg to about 50 mg, about 30 mg to about 40 mg, about 40 mg to about 225 mg, about 40 mg to about 200 mg, about 40 mg to about 180 mg, about 40 mg to about 160 mg, about 40 mg to about 140 mg, about 40mg to about 120mg, about 40mg to about 100mg, about 40mg to about 90mg, about 40mg to about 80mg, about 40mg to about 70mg, about 40mg to about 60mg, about 40mg to about 50mg, about 50mg to about 225mg, about 50mg to about 200mg, about 50mg to about 180mg, about 50mg to about 160mg, about 50mg to about 140mg, about 50mg to about 120mg, about 50mg to about 100mg, about 50mg to about 90mg, about 50mg to about 80mg, about 50mg to about 70mg, about 50mg to about 60mg, about 60mg to about 225mg, about 60mg to about 200mg, about 6 0mg to about 180mg, about 60mg to about 160mg, about 60mg to about 140mg, about 60mg to about 120mg, about 60mg to about 100mg, about 60mg to about 90mg, about 60mg to about 80mg, about 60mg to about 70mg, about 70mg to about 225mg, about 70mg to about 200mg, about 70mg to about 180mg, about 70mg to about 160mg, about 70mg to about 140mg, about 70mg to about 120mg, about 70mg to about 100mg, about 70mg to about 90mg, about 70mg to about 80mg, about 70mg to about 225mg, about 80mg to about 200mg, about 80mg to about 18 0mg, about 80mg to about 160mg, about 80mg to about 140mg, about 80mg to about 120mg, about 80mg to about 100mg, about 80mg to about 90mg, about 70mg to about 225mg, about 90mg to about 200mg, about 90mg to about 180mg, about 90mg to about 160mg, about 90mg to about 140mg, about 90mg to about 120mg, about 90mg to about 100mg, about 100mg to about 225mg, about 100mg to about 200mg, about 100mg to about 180mg, about 100mg to about 160mg, about 100mg to about 140mg, about 100mg to about 120mg,The amount of furosemide in the unit liquid pharmaceutical formulation described herein can be about 1 mg to about 225 mg, about 120 mg to about 200 mg, about 120 mg to about 180 mg, about 120 mg to about 160 mg, about 120 mg to about 140 mg, about 140 mg to about 225 mg, about 140 mg to about 200 mg, about 140 mg to about 180 mg, about 140 mg to about 160 mg, about 160 mg to about 225 mg, about 160 mg to about 200 mg, about 160 mg to about 180 mg, about 180 mg to about 225 mg, about 180 mg to about 200 mg, or about 200 mg to about 225 mg. In certain embodiments, the amount of furosemide in the unit liquid pharmaceutical formulation described herein can be about 1 mg to about 250 mg.

[0242] In certain embodiments, the amount of furosemide in the unit liquid pharmaceutical formulations described herein can be greater than about 1 mg, greater than about 5 mg, greater than about 10 mg, greater than about 20 mg, greater than about 30 mg, greater than about 40 mg, greater than about 50 mg, greater than about 60 mg, greater than about 70 mg, greater than about 80 mg, greater than about 90 mg, greater than about 100 mg, greater than about 110 mg, greater than about 120 mg, greater than about 130 mg, greater than about 140 mg, greater than about 150 mg, greater than about 160 mg, greater than about 170 mg, greater than about 180 mg, greater than about 190 mg, greater than about 200 mg, greater than about 210 mg, greater than about 220 mg, greater than about 230 mg, greater than about 240 mg, or greater than about 250 mg.

[0243] In certain embodiments, the amount of furosemide in the unit liquid pharmaceutical formulations described herein is about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 22 mg, about 24 mg, about 26 mg, about 28 mg, about 30 mg, about 32 mg, about 34 mg, about 36 mg, about 38 mg, about 40 mg, about 42 mg, about 44 mg, about 45 mg, about 46 mg, about 47 mg, about 48 mg, about 49 mg, about 50 mg, about 51 mg, about 52 mg, about 53 mg, about 54 mg, about 55 mg, about 56 mg, about 57 mg, about 58 mg, about 59 mg, about 60 mg, about 61 mg, about 62 mg, about 63 mg, about 64 mg, about 65 mg, about 66 mg, about 67 mg, about 68 mg, about 69 mg, about 70 mg, about 71 mg, about 72 mg, about 73 mg, about 74 mg, about 75 mg, about 76 mg, about 77 mg, about 78 mg, about 79 mg, about 80 mg, about 81 mg, about 82 mg, about 83 mg, about 84 mg, about 85 mg, about 86 mg, about 87 mg, about 88 mg, about 89 mg, about 90 mg, about 91 mg, about 92 mg, about 93 mg, about 94 mg, about 95 mg, In certain embodiments, the amount of furosemide in the unit liquid pharmaceutical formulations described herein can be about 80 mg.

[0244] In certain embodiments, the amount of bumetanide in the unit liquid pharmaceutical formulation described herein is from about 0.025 mg to about 65 mg, from about 0.1 mg to about 65 mg, from about 0.5 mg to about 65 mg, from about 1 mg to about 65 mg, from about 5 mg to about 65 mg, from about 10 mg to about 65 mg, from about 20 mg to about 65 mg, from about 30 mg to about 65 mg, from about 40 mg to about 65 mg, from about 50 mg to about 65 mg, from about 60 mg to about 65 mg, from about 0.025 mg to about 60 mg, from about 0.025 mg to about 50 mg, from about 0.025 mg to about 40 mg, mg, about 0.025mg to about 30mg, about 0.025mg to about 20mg, about 0.025mg to about 10mg, about 0.025mg to about 5mg, about 0.025mg to about 1mg, about 0.025mg to about 0.5mg, about 0.025mg to about 0.1mg, about 0.1 mg to about 60 mg, about 0.1 mg to about 50 mg, about 0.1 mg to about 40 mg, about 0.1 mg to about 30 mg, about 0.1 mg to about 20 mg, about 0.1 mg to about 10 mg, about 0.1 mg to about 5 mg, about 0.1 mg to about 1 mg, about 0.5 mg to about 60mg, about 0.5mg to about 50mg, about 0.5mg to about 40mg, about 0.5mg to about 30mg, about 0.5mg to about 20mg, about 0.5mg to about 10mg, about 0.5mg to about 10mg, about 0.5mg to about 5mg, about 0.5mg to about 1mg, about 1 mg ~ about 60mg, about 1mg - about 50mg, about 1mg - about 40mg, about 1mg - about 30mg, about 1mg - about 20mg, about 1mg - about 10mg, about 1mg - about 5mg, about 5mg - about 60mg, about 5mg - about 50mg, about 5mg - about 40mg, about 5 In certain embodiments, the amount of bumetanide in a unit liquid pharmaceutical formulation described herein can be from about 0.025 mg to about 65 mg.

[0245] In certain embodiments, the amount of bumetanide in the unit liquid pharmaceutical formulations described herein can be greater than about 0.025 mg, greater than about 1 mg, greater than about 5 mg, greater than about 10 mg, greater than about 20 mg, greater than about 30 mg, greater than about 40 mg, greater than about 50 mg, or greater than about 60 mg.

[0246] In certain embodiments, the amount of bumetanide in the unit liquid pharmaceutical formulation described herein is about 0.025 mg, about 0.05 mg, about 0.075 mg, about 0.1 mg, about 0.25 mg, about 0.5 mg, about 0.75 mg, about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, about 25 mg, about 26 mg, about 27 mg, about 28 mg, about 29 mg, about 30 mg, about 31 mg, about 32 mg, about 33 mg, about 34 mg, about 35 mg, about 36 mg, about 37 mg, about 38 mg, about 39 mg, about 40 mg, about 41 mg, about 42 mg, about 43 mg, about 44 mg, about 45 mg, about 46 mg, about 47 mg, about 48 mg, about 49 mg, about 50 mg, about 51 mg, about 52 mg, about 53 mg, about 54 mg, about 55 mg, about 56 mg, about 57 mg, about 58 mg, about 59 mg, about 60 mg, about 61 mg, about 62 mg, about 63 mg, about 64 mg, about 65 mg, about 66 mg, about 67 mg, about 68 mg, about 69 mg, about 70 mg, about 71 mg, about 72 mg, about 73 mg, about 74 mg, about 75 mg, It can be 3 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 22 mg, about 24 mg, about 26 mg, about 28 mg, about 30 mg, about 32 mg, about 34 mg, about 36 mg, about 38 mg, about 40 mg, about 42 mg, about 44 mg, about 46 mg, about 48 mg, about 50 mg, about 55 mg, about 60 mg, or about 65 mg.

[0247] In certain embodiments, the amount of torsemide in the unit liquid pharmaceutical formulation described herein is from about 0.5 mg to about 125 mg, from about 1 mg to about 125 mg, from about 5 mg to about 125 mg, from about 10 mg to about 125 mg, from about 20 mg to about 125 mg, from about 30 mg to about 125 mg, from about 40 mg to about 125 mg, from about 50 mg to about 125 mg, from about 75 mg to about 125 mg, from about 100 mg to about 125 mg, from about 0.5 mg to about 100mg, about 0.5mg to about 75mg, about 0.5mg to about 50mg, about 0.5mg to about 40mg, about 0.5mg to about 30mg, about 0.5mg to about 20mg, about 0.5mg to about 10mg, about 0.5mg ~5mg, approx. 0.5mg~approx.1mg, approx.1mg~approx.100mg, approx.1mg~approx.75mg, approx.1mg~approx.50mg, approx.1mg~approx.40mg, approx.1mg~approx.30mg, approx.1mg~approx.20mg, approx.1mg~ About 10mg, about 1mg to about 5mg, about 5mg to about 100mg, about 5mg to about 75mg, about 5mg to about 50mg, about 5mg to about 40mg, about 5mg to about 30mg, about 5mg to about 20mg, about 5mg to about 1 0mg, about 10mg to about 100mg, about 10mg to about 75mg, about 10mg to about 50mg, about 10mg to about 40mg, about 10mg to about 30mg, about 10mg to about 20mg, about 20mg to about 100mg, It can be about 20 mg to about 75 mg, about 20 mg to about 50 mg, about 20 mg to about 40 mg, about 20 mg to about 30 mg, about 30 mg to about 100 mg, about 30 mg to about 75 mg, about 30 mg to about 50 mg, about 30 mg to about 40 mg, about 40 mg to about 100 mg, about 40 mg to about 75 mg, about 40 mg to about 50 mg, about 50 mg to about 100 mg, about 50 mg to about 75 mg, or about 75 mg to about 100 mg.

[0248] In certain embodiments, the amount of torsemide in the liquid pharmaceutical formulations described herein can be greater than about 0.5 mg, greater than about 1 mg, greater than about 5 mg, greater than about 10 mg, greater than about 20 mg, greater than about 30 mg, greater than about 40 mg, greater than about 50 mg, greater than about 60 mg, greater than about 70 mg, greater than about 80 mg, greater than about 90 mg, greater than about 100 mg, or greater than about 125 mg.

[0249] In certain embodiments, the amount of torsemide in the unit liquid pharmaceutical formulations described herein can be about 0.5 mg, about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, or about 125 mg.

[0250] Other excipients for unit liquid pharmaceutical preparations It should be understood that the excipients, amounts and concentrations, and other conditions and parameters described herein for liquid pharmaceutical formulations are equally applicable to the unit liquid pharmaceutical formulations described herein as if those excipients, amounts and concentrations, and other conditions and parameters were described herein in this section, but for the sake of brevity, will not be repeated.

[0251] In particular, the pH, pharmaceutically acceptable buffers and their concentrations, pharmaceutically acceptable pH adjusting agents and their concentrations, antioxidants and their concentrations, osmolality, and additional pharmaceutically acceptable excipients (such as benzyl alcohol, cyclodextrins and cyclodextrin derivatives) and their concentrations described herein for the liquid pharmaceutical formulations are equally applicable to the unit liquid pharmaceutical formulations described herein.

[0252] Exemplary Furosemide Unit Liquid Pharmaceutical Formulations In various embodiments, provided herein is a unit liquid pharmaceutical formulation for treating a disease or disorder described herein (e.g., congestion, edema, fluid overload, or hypertension) in a patient in need thereof, comprising a therapeutically effective amount of furosemide and a pharmaceutically acceptable excipient. The unit liquid pharmaceutical formulation may include, inter alia, a pharmaceutically acceptable pH adjuster, an antioxidant, an osmolality adjuster, and / or a pharmaceutically acceptable buffer, as described herein.

[0253] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer.

[0254] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) tromethamine, or a pharmaceutically acceptable salt thereof.

[0255] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof.

[0256] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0257] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0258] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0259] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0260] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0261] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) pharmaceutically acceptable pH adjusters, including sodium hydroxide and hydrochloric acid.

[0262] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an antioxidant.

[0263] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0264] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant.

[0265] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0266] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0267] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0268] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0269] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0270] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0271] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) sodium chloride, including

[0272] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) one or more additional pharmaceutically acceptable excipients.

[0273] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0274] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0275] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer containing a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine, or a pharmaceutically acceptable salt thereof; and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0276] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0277] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0278] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) cyclodextrin or a derivative thereof.

[0279] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0280] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) Cyclodextrin or a derivative thereof.

[0281] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0282] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) Cyclodextrin or a derivative thereof.

[0283] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0284] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) benzyl alcohol.

[0285] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof, and (ii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0286] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) benzyl alcohol, including

[0287] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0288] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) benzyl alcohol, including

[0289] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0290] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof; (iii) benzyl alcohol, (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0291] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof; (iii) about 0.1% (w / w) to about 10% (w / w) of benzyl alcohol; (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0292] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0293] Exemplary Bumetanide Unit Liquid Pharmaceutical Formulations In various embodiments, provided herein is a unit liquid pharmaceutical formulation for treating a disease or disorder described herein (e.g., congestion, edema, fluid overload, or hypertension) in a patient in need thereof, comprising a therapeutically effective amount of bumetanide and a pharmaceutically acceptable excipient. The unit liquid pharmaceutical formulation may include, inter alia, a pharmaceutically acceptable pH adjuster, antioxidant, osmolality adjuster, and / or a pharmaceutically acceptable buffer, as described herein.

[0294] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer.

[0295] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) bumetanide, or a pharmaceutically acceptable salt thereof, in a therapeutically effective amount; and (ii) tromethamine, or a pharmaceutically acceptable salt thereof.

[0296] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof.

[0297] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0298] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0299] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0300] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0301] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0302] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) pharmaceutically acceptable pH adjusters, including sodium hydroxide and hydrochloric acid.

[0303] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an antioxidant.

[0304] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0305] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant.

[0306] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0307] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0308] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0309] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0310] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0311] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0312] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) sodium chloride, including

[0313] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) one or more additional pharmaceutically acceptable excipients.

[0314] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0315] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0316] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer containing a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine, or a pharmaceutically acceptable salt thereof; and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0317] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0318] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0319] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) bumetanide, or a pharmaceutically acceptable salt thereof, in a therapeutically effective amount; and (ii) cyclodextrin or a derivative thereof.

[0320] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof, and (ii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0321] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) Cyclodextrin or a derivative thereof.

[0322] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0323] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) Cyclodextrin or a derivative thereof.

[0324] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0325] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) bumetanide, or a pharmaceutically acceptable salt thereof, in a therapeutically effective amount; and (ii) benzyl alcohol.

[0326] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof, and (ii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0327] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) benzyl alcohol, including

[0328] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0329] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) benzyl alcohol, including

[0330] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0331] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof; (iii) benzyl alcohol, (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0332] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof; (iii) about 0.1% (w / w) to about 10% (w / w) of benzyl alcohol; (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0333] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.025 mg to about 65 mg of bumetanide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0334] Exemplary Torsemide Unit Liquid Pharmaceutical Formulations In various embodiments, provided herein is a unit liquid pharmaceutical formulation for treating a disease or disorder described herein (e.g., congestion, edema, fluid overload, or hypertension) in a patient in need thereof, comprising a therapeutically effective amount of torsemide and a pharmaceutically acceptable excipient. The unit liquid pharmaceutical formulation may include, inter alia, a pharmaceutically acceptable pH adjuster, antioxidant, osmolality adjuster, and / or a pharmaceutically acceptable buffer, as described herein.

[0335] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer.

[0336] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) tromethamine, or a pharmaceutically acceptable salt thereof.

[0337] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof.

[0338] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0339] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0340] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0341] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) a pharmaceutically acceptable pH adjusting agent.

[0342] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) A pharmaceutically acceptable pH adjuster selected from the group consisting of acetic acid, citric acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, aqueous ammonia, ammonium carbonate, diethanolamine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, trolamine, and combinations thereof.

[0343] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) pharmaceutically acceptable pH adjusters, including sodium hydroxide and hydrochloric acid.

[0344] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an antioxidant.

[0345] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0346] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant.

[0347] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) about 0.01% (w / w) to about 2% (w / w) of an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, ethylenediaminetetraacetic acid (EDTA), and combinations thereof.

[0348] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0349] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0350] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0351] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) an osmolality adjuster.

[0352] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer solution comprising a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and a combination thereof; and (iii) an osmolality adjuster selected from the group consisting of sodium chloride, potassium chloride, isosorbide, mannitol, xylitol, and combinations thereof.

[0353] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) sodium chloride, including

[0354] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) one or more additional pharmaceutically acceptable excipients.

[0355] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer comprising a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and combinations thereof; and (iii) one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0356] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0357] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer containing a buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine, or a pharmaceutically acceptable salt thereof; and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0358] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients.

[0359] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof; and (iii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and combinations thereof.

[0360] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) cyclodextrin or a derivative thereof.

[0361] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0362] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) Cyclodextrin or a derivative thereof.

[0363] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0364] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) Cyclodextrin or a derivative thereof.

[0365] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 5% to about 50% (w / w) of cyclodextrin or a derivative thereof.

[0366] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) benzyl alcohol.

[0367] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof, and (ii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0368] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) a pharmaceutically acceptable buffer, and (iii) benzyl alcohol, including

[0369] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0370] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) benzyl alcohol, including

[0371] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.1% (w / w) to about 10% (w / w) benzyl alcohol.

[0372] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) a therapeutically effective amount of torsemide, or a pharmaceutically acceptable salt thereof; (ii) tromethamine, or a pharmaceutically acceptable salt thereof; (iii) benzyl alcohol, (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0373] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof; (iii) about 0.1% (w / w) to about 10% (w / w) of benzyl alcohol; (iv) sodium chloride, and (v) pH adjusters including sodium hydroxide and / or hydrochloric acid.

[0374] In various embodiments, the unit liquid pharmaceutical formulation comprises: (i) about 0.5 mg to about 125 mg of torsemide, or a pharmaceutically acceptable salt thereof; (ii) about 10 mM to about 250 mM tromethamine, or a pharmaceutically acceptable salt thereof, and (iii) about 0.01% (w / w) to about 2% (w / w) sodium disulfite.

[0375] Treatment method In one aspect, the liquid pharmaceutical formulations or unit liquid pharmaceutical formulations described herein may be used for the treatment or prevention of a variety of diseases and disorders, including, but not limited to, congestion, edema, fluid overload, and / or hypertension, in patients in need thereof.

[0376] In various embodiments, the method comprises administering to the patient a liquid pharmaceutical formulation described herein.

[0377] In various embodiments, the method comprises administering to the patient a unit liquid pharmaceutical formulation described herein.

[0378] In certain embodiments, the liquid pharmaceutical formulations described herein include a loop diuretic, such as furosemide, as the only therapeutically active agent in the liquid pharmaceutical formulation. In some embodiments, the liquid pharmaceutical formulations described herein further include a second therapeutic agent. In certain embodiments, the liquid pharmaceutical formulation and the second therapeutic agent are administered simultaneously, together or separately, or separately at different times as part of a regimen.

[0379] In certain embodiments, the liquid pharmaceutical formulations described herein can be administered parenterally, e.g., by infusion or injection, including subcutaneous administration as appropriate. For example, the liquid pharmaceutical formulation can be administered, for example, by subcutaneous injection or delivery, or intravenous injection or delivery. In some embodiments, the liquid pharmaceutical formulation is administered intravenously to a patient. In some embodiments, the liquid pharmaceutical formulation is administered to a patient by intramuscular injection, subcutaneous injection, or subcutaneous infusion. In some embodiments, the liquid pharmaceutical formulation is administered to a patient by subcutaneous infusion using a body-worn subcutaneous delivery system. In some embodiments, the liquid pharmaceutical formulation is administered to a patient by subcutaneous infusion using a wearable subcutaneous delivery system. In some embodiments, the liquid pharmaceutical formulation is administered to a patient by subcutaneous infusion using a pump device. In some embodiments, the pump device is a micropump device or a patch device. In some embodiments, the pump device is a patch device. In some embodiments, the liquid pharmaceutical formulation is administered to a patient by intramuscular or subcutaneous injection using an autoinjector. In some embodiments, the autoinjector is a disposable autoinjector.

[0380] In certain embodiments, the liquid pharmaceutical formulations described herein are administered to a patient by subcutaneous infusion over about 0.5 hours, about 1.0 hours, about 1.5 hours, about 2.0 hours, about 4.0 hours, or about 8.0 hours. In certain embodiments, the liquid pharmaceutical formulations described herein are administered to a patient by subcutaneous infusion over about 1 minute, about 2 minutes, about 3 minutes, about 4 minutes, about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 40 minutes, about 50 minutes, about 60 minutes, about 90 minutes, about 120 minutes, about 240 minutes, or about 480 minutes. In certain embodiments, the liquid pharmaceutical formulations described herein are administered to a patient by subcutaneous injection over a period of 30 seconds or less (e.g., 1 second, 2 seconds, 3 seconds, 4 seconds, 5 seconds, 6 seconds, 7 seconds, 8 seconds, 9 seconds, 10 seconds, 11 seconds, 12 seconds, 13 seconds, 14 seconds, 15 seconds, 16 seconds, 17 seconds, 18 seconds, 19 seconds, 20 seconds, 21 seconds, 22 seconds, 23 seconds, 24 seconds, 25 seconds, 26 seconds, 27 seconds, 28 seconds, 29 seconds, or 30 seconds).

[0381] In certain embodiments, the unit liquid pharmaceutical formulations described herein include a loop diuretic, such as furosemide, as the only therapeutically active agent in the unit liquid pharmaceutical formulation. In some embodiments, the unit liquid pharmaceutical formulations described herein further include a second therapeutic agent. In some embodiments, the unit liquid pharmaceutical formulation and the second therapeutic agent are administered simultaneously, together or separately, or separately at different times, as part of a regimen.

[0382] In certain embodiments, the unit liquid pharmaceutical formulations described herein can be administered parenterally, e.g., by infusion, injection, or implantation, including subcutaneous administration as appropriate. For example, the unit liquid pharmaceutical formulation can be administered, e.g., by subcutaneous injection or delivery, or intravenous injection or delivery. In some embodiments, the unit liquid pharmaceutical formulation is administered intravenously to a patient. In some embodiments, the unit liquid pharmaceutical formulation is administered to a patient by subcutaneous injection or infusion. In some embodiments, the unit liquid pharmaceutical formulation is administered to a patient by subcutaneous infusion using a body-worn subcutaneous delivery system. In some embodiments, the unit liquid pharmaceutical formulation is administered to a patient by subcutaneous infusion using a wearable subcutaneous delivery system. In certain embodiments, the unit liquid pharmaceutical formulation is administered to a patient by subcutaneous infusion using a pump device. In some embodiments, the pump device is a micropump device or a patch device. In some embodiments, the pump device is a patch device.

[0383] In certain embodiments, the unit liquid pharmaceutical formulations described herein are administered to a patient by subcutaneous infusion over a period of about 0.5 hours, about 1 hour, about 1.5 hours, about 2 hours, about 4 hours, or about 8 hours. In certain embodiments, the unit liquid pharmaceutical formulations described herein are administered to a patient by subcutaneous infusion over a period of 30 seconds or less.

[0384] When administered for the treatment or prevention of a disease or disorder disclosed herein, it will be understood that an effective dosage may vary depending on many factors, such as the particular compound or therapeutic combination used, the method of administration, and the severity of the condition being treated, as well as various physical factors related to the individual being treated. For therapeutic use, the liquid pharmaceutical formulations or unit liquid pharmaceutical formulations described herein may be provided to a patient already suffering from the disease or disorder in question in an amount sufficient to cure or at least partially ameliorate the symptoms of the disease or disorder and its complications. The dosage used to treat a particular individual must typically be subjectively determined by the attending physician. The variables involved include the patient's particular condition and condition, as well as their size, age, and response pattern. In some embodiments, an effective amount is an amount sufficient to cure or at least partially ameliorate the symptoms of a disease or disorder and its complications. In some embodiments, an effective amount is an amount sufficient to cure or at least partially ameliorate the symptoms of a disease or disorder and its complications.

[0385] kit In one aspect, the present invention provides kits for the treatment or prevention of various diseases and disorders, including but not limited to, congestion, edema, fluid overload, or hypertension, in a patient in need thereof.

[0386] In various embodiments, the kit comprises the liquid pharmaceutical formulation described herein. In certain embodiments, the kit comprises one or more unit doses of the liquid pharmaceutical formulation. In certain embodiments, the kit further comprises a medical device. In certain embodiments, the kit further comprises instructions for treating the disease or disorder of the present invention.

[0387] In various embodiments, the kit comprises a unit liquid pharmaceutical formulation described herein. In certain embodiments, the kit comprises one or more units of the liquid pharmaceutical formulation. In some embodiments, the kit comprises one, two, three, or more units of the liquid pharmaceutical formulation. In certain embodiments, the kit further comprises a medical device. In certain embodiments, the kit further comprises instructions for treating a disease or disorder of the present invention.

[0388] Several medical devices have been proposed to facilitate self-administration of pharmaceutical formulations. Such devices may include a reservoir (e.g., pre-filled) containing the liquid pharmaceutical formulation described herein to be administered. For example, a micropump can provide precise subcutaneous administration of a small amount of liquid pharmaceutical formulation. Such a micropump can be small and portable. Another type of device useful for subcutaneous delivery or administration of pharmaceutical formulations is often referred to as a patch device, a body-worn subcutaneous delivery system, or a wearable subcutaneous delivery system (e.g., a pump-patch device). Patch devices are typically applied directly to the patient's skin. One type of device useful for intramuscular or subcutaneous delivery of pharmaceutical formulations is an autoinjector.

[0389] Thus, in various embodiments, a medical device such as a micropump or patch device may include a reservoir containing a pharmaceutical formulation, a hypodermic needle configured for removable insertion into a patient's skin, a micropump having an inlet in fluid communication with the reservoir and an outlet in fluid communication with the hypodermic needle, a control system configured to control the micropump to deliver the pharmaceutical formulation from the reservoir to the hypodermic needle (thereby administering the pharmaceutical formulation subcutaneously to the patient), and a housing for supporting the reservoir, hypodermic needle, micropump, and control system, wherein the housing is portable and adapted for contact with a patient's skin. The liquid pharmaceutical formulation contained within the reservoir may be any of the liquid pharmaceutical formulations or unit liquid pharmaceutical formulations described herein.

[0390] In certain embodiments, the medical device can be of unitary construction. Such medical devices can be single-use or one-time use. In certain embodiments, the medical device can be of multi-part construction. In such medical devices, there can be disposable or reusable parts or components. For example, a housing defining or containing a reservoir can be a disposable or reusable component of the medical device. In some embodiments, a disposable or reusable housing defining or containing a reservoir can contain a pharmaceutical formulation of the present teachings. In various embodiments, a hypodermic needle can be a disposable component of the medical device.

[0391] In certain embodiments, the medical device is a pump device. In some embodiments, the pump device is a micropump device or a patch device. In some embodiments, the pump device is a patch device. In certain embodiments, the medical device is selected from the group including a needle and syringe set, an autoinjector, a single-use fixed-dose injection pen, a multi-use fixed-dose injection pen, a single-use variable-dose injection pen, or a multi-use variable-dose injection pen. [Example]

[0392] The invention generally described herein will be more readily understood by reference to the following examples, which are intended merely to illustrate certain aspects and embodiments of the invention and are not intended to limit the invention.

[0393] Example 1. Manufacturing process of furosemide liquid pharmaceutical formulation The following examples outline the manufacturing process for all exemplified liquid pharmaceutical formulations of furosemide.

[0394] The corresponding amounts of ingredients are listed in the formulations disclosed in Table 1. Tromethamine and sodium disulfite were added to the appropriate amount of water for injection (WFI) and mixed until dissolved. Sodium hydroxide (NaOH) was added. Approximately 1 / 3 of the total amount of furosemide bulk drug was added and mixed until dissolved. Benzyl alcohol was added and mixed until uniform. NaOH was added. Approximately 1 / 3 of the total amount of furosemide bulk drug was added and mixed until dissolved. NaOH was added. The remaining furosemide bulk drug was added and mixed until dissolved. A pH sample was taken, and the solution was adjusted to a pH of 7.20-7.60 with additional NaOH. After pH adjustment, WFI was added to the resulting solution until the final weight was reached and mixed. The solution was filtered through a 0.22 μm PVDF filter and filled into a glass syringe. [Table 1]

[0395] Incorporation by Reference The entire disclosure of each of the patent documents and scientific articles referenced herein is incorporated by reference for all purposes.

[0396] equivalent The present disclosure may be embodied in other specific forms without departing from its spirit or essential characteristics. Accordingly, the foregoing embodiments should be considered in all respects as illustrative rather than limiting of the disclosure described herein. The scope of the present disclosure is, therefore, indicated by the appended claims, rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

1. (i) a therapeutically effective amount of furosemide, or a pharmaceutically acceptable salt thereof; (ii) an antioxidant; and (iii) a pharmaceutically acceptable buffer.

2. 10. The liquid pharmaceutical formulation of claim 1, further comprising (iv) one or more additional pharmaceutically acceptable excipients.

3. 3. The liquid pharmaceutical formulation of claim 2, wherein the one or more additional pharmaceutically acceptable excipients are selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and any combination thereof.

4. 4. The liquid pharmaceutical formulation of claim 2 or 3, wherein the one or more additional pharmaceutically acceptable excipients comprise benzyl alcohol.

5. 5. The liquid pharmaceutical formulation according to claim 4, wherein the amount of benzyl alcohol in the liquid pharmaceutical formulation is from about 0.1% (w / w) to about 10% (w / w).

6. The liquid pharmaceutical formulation according to any one of claims 1 to 5, wherein the concentration of said pharmaceutically acceptable buffer in said liquid pharmaceutical formulation is from about 10 mM to about 500 mM.

7. 7. The liquid pharmaceutical formulation of any one of claims 1-6, wherein the pharmaceutically acceptable buffer comprises a buffering agent selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and any combination thereof.

8. 8. The liquid pharmaceutical formulation of claim 7, wherein the buffering agent is tromethamine or a pharmaceutically acceptable salt thereof.

9. 9. The liquid pharmaceutical formulation according to claim 8, wherein the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulation is from about 10 mM to about 200 mM.

10. 10. The liquid pharmaceutical formulation according to claim 8, wherein the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulation is from about 25 mM to about 150 mM.

11. The liquid pharmaceutical formulation according to any one of claims 1 to 10, wherein the amount of said antioxidant in said liquid pharmaceutical formulation is from about 0.05% (w / w) to about 2% (w / w).

12. 12. The liquid pharmaceutical formulation of any one of claims 1-11, wherein the antioxidant is selected from the group consisting of sodium disulfite, sodium monothioglycerol bisulfite, methionine, EDTA, and combinations thereof.

13. 13. The liquid pharmaceutical formulation according to any one of claims 1 to 12, wherein the concentration of furosemide in said liquid pharmaceutical formulation is from about 1 mg / mL to about 250 mg / mL.

14. The liquid pharmaceutical formulation according to any one of claims 1 to 13, wherein the pH of the liquid pharmaceutical formulation is from about 6.5 to about 8.

5.

15. The liquid pharmaceutical formulation according to any one of claims 1 to 14, wherein the pH of the liquid pharmaceutical formulation is from about 7 to about 8.

3.

16. (i) about 1 mg to about 250 mg of furosemide, or a pharmaceutically acceptable salt thereof; (ii) about 0.1% (w / w) to about 30% (w / w) of one or more additional pharmaceutically acceptable excipients selected from the group consisting of ethanol, benzyl alcohol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, sodium carbonate, mannitol, lactose, dextrose, polyethylene glycol (PEG), propylene glycol, polysorbate, polyvinylpyrrolidone (PVP), cyclodextrin or a derivative thereof, vitamin E or a derivative thereof, and any combination thereof; (iii) about 0.05% (w / w) to about 2% (w / w) of an antioxidant selected from the group consisting of sodium disulfite, sodium bisulfite monothioglycerol, methionine, EDTA, and combinations thereof; (iv) about 10 mM to about 500 mM of a pharmaceutically acceptable buffer selected from the group consisting of histidine, citrate, sodium phosphate, potassium phosphate, tromethamine or a pharmaceutically acceptable salt thereof, and any combination thereof; The liquid pharmaceutical formulation has a pH of about 6.5 to about 8.

5.

17. The liquid pharmaceutical formulation of any one of claims 1-15 or the unit liquid pharmaceutical formulation of claim 16, further comprising one or more of water, a pH adjuster, and an osmolality adjuster.

18. 18. The liquid pharmaceutical formulation or unit liquid pharmaceutical formulation of claim 17, wherein the pH adjuster is selected from the group consisting of potassium hydroxide, sodium hydroxide, hydrochloric acid, and combinations thereof, and the osmolality adjuster is selected from the group consisting of sodium chloride, potassium chloride, and combinations thereof.

19. 19. A method of treating congestion, edema, fluid overload, or hypertension in a patient in need thereof, said method comprising administering to said patient a liquid pharmaceutical formulation according to any one of claims 1-15, 17 and 18, or a unit liquid pharmaceutical formulation according to any one of claims 16-18.

20. 20. The method of claim 19, wherein the liquid pharmaceutical formulation is administered to the patient by subcutaneous injection or subcutaneous infusion.

21. 21. The method of claim 20, wherein the liquid pharmaceutical formulation is administered to the patient by subcutaneous injection using a body-worn subcutaneous delivery system.

22. 22. The method of claim 21, wherein the body-worn subcutaneous delivery system is a pump device.

23. 20. The method of claim 19, wherein the unit liquid pharmaceutical formulation is administered to the patient by subcutaneous injection or subcutaneous infusion.

24. 24. The method of claim 23, wherein the unit liquid pharmaceutical formulation is administered to the patient by subcutaneous infusion using a body-worn subcutaneous delivery system.

25. 25. The method of claim 24, wherein the body-worn subcutaneous delivery system is a pump device.

26. A kit for treating congestion, edema, fluid overload, or hypertension, comprising a liquid pharmaceutical formulation according to any one of claims 1 to 15, 17, and 18, or a unit liquid pharmaceutical formulation according to any one of claims 16 to 18.

27. 27. The kit of claim 26, comprising one, two, three or more units.

28. 28. The kit of claim 26 or 27, further comprising a body-worn subcutaneous delivery system.

29. 29. The kit of claim 28, wherein the body-worn subcutaneous delivery system is a pump device.

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