Concentrated liquid pharmaceutical formulations of furosemide and methods of administering the same

1. A unit liquid pharmaceutical formulation comprising:

(i) from about 10 mg to about 200 mg furosemide, or a pharmaceutically acceptable salt thereof;

(ii) from about 0.1% (w/w) to about 30% (w/w) of one or more pharmaceutically acceptable excipients; and

(iii) from about 25 mM to about 150 mM of a pharmaceutically acceptable buffer comprising tromethamine or a pharmaceutically acceptable salt thereof,

wherein the concentration of furosemide in the liquid pharmaceutical formulation is from about 60 mg/mL to about 250 mg/mL and wherein the pH of the liquid pharmaceutical formulation is from about 6.5 to about 8.5.

2. A unit liquid pharmaceutical formulation comprising:

(i) from about 10 mg to about 200 mg furosemide, or a pharmaceutically acceptable salt thereof;

(ii) from about 0.1% (w/w) to about 10% (w/w) benzyl alcohol; and

(iii) from about 25 mM to about 150 mM tromethamine or a pharmaceutically acceptable salt thereof,

wherein the concentration of furosemide in the unit liquid pharmaceutical formulation is from about 60 mg/mL to about 200 mg/mL and the pH of the liquid pharmaceutical formulation is from about 6.5 to about 8.5.

3. The unit liquid pharmaceutical formulation of claim 2 , wherein the pH of the liquid pharmaceutical formulation is from about 7 to about 8.

4. The unit liquid pharmaceutical formulation of claim 2 , wherein the amount of benzyl alcohol in the unit liquid pharmaceutical formulation is from about 0.5% (w/w) to about 5% (w/w).

5. The unit liquid pharmaceutical formulation of claim 1 , further comprising one of more of water; a pH adjuster; and an osmolarity adjuster.

6. The unit liquid pharmaceutical formulation of claim 5 , wherein the pH adjuster is selected from the group consisting of potassium hydroxide, sodium hydroxide, hydrochloric acid, and combinations thereof; and the osmolarity adjuster is selected from the group consisting of sodium chloride, potassium chloride, and combinations thereof.

7. A method of treating congestion, edema, fluid overload, or hypertension in a patient in need thereof, the method comprising administering to the patient the unit liquid pharmaceutical formulation of claim 1 .

8. The method of claim 7 , wherein the unit liquid pharmaceutical formulation is administered to the patient by subcutaneous injection.

9. A kit for the treatment of congestion, edema, fluid overload, or hypertension comprising the unit liquid pharmaceutical formulation of claim 1 .

10. The kit of claim 9 , comprising one, two, three or more units of the unit liquid pharmaceutical formulation.

11. The unit liquid pharmaceutical formulation of claim 1 , wherein the liquid pharmaceutical formulation comprises from about 25 mM to about 100 mM of a pharmaceutically acceptable buffer comprising tromethamine or a pharmaceutically acceptable salt thereof.

12. The unit liquid pharmaceutical formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients is selected from the group consisting of ethanol, benzyl alcohol, glycerin, sodium chloride, a polyethylene glycol (PEG), propylene glycol, a polysorbate, a polyvinylpyrrolidone (PVP), a cyclodextrin, and any combination thereof.

13. The unit liquid pharmaceutical formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises benzyl alcohol.

14. The unit liquid formulation of claim 13 , wherein the one or more pharmaceutically acceptable excipients further comprises a polysorbate.

15. The unit liquid pharmaceutical formulation of claim 12 , wherein the one or more pharmaceutically acceptable excipients is benzyl alcohol, a polysorbate, or a combination thereof.

16. The unit liquid pharmaceutical formulation of claim 2 , further comprising a polysorbate.

17. The unit liquid pharmaceutical formulation of claim 1 , wherein the volume of the unit liquid pharmaceutical formulation is about 2 mL, about 1.5 mL, about 1.0 mL, or about 0.5 mL.

18. The unit liquid pharmaceutical formulation of claim 17 , wherein the volume is pre-loaded in a reservoir of a medical device.

19. The unit liquid pharmaceutical formulation of claim 18 , wherein the medical device is selected from the group consisting of a needle and syringe set, an autoinjector, a single use fixed dose injection pen, a multiuse fixed dose injection pen, a single use variable dose injection pen, and a multiuse variable dose injection pen.

20. The unit liquid pharmaceutical formulation of claim 1 , wherein the volume of the unit liquid pharmaceutical formulation is from about 0.5 mL to about 10 mL.

21. The unit liquid pharmaceutical formulation of claim 20 , wherein the volume is pre-loaded in a reservoir of a medical device.

22. The unit liquid pharmaceutical formulation of claim 21 , wherein the medical device is selected from the group consisting of a needle and syringe set, an autoinjector, a single use fixed dose injection pen, a multiuse fixed dose injection pen, a single use variable dose injection pen, and a multiuse variable dose injection pen.

23. The unit liquid pharmaceutical formulation of claim 1 , wherein the volume of the unit liquid pharmaceutical formulation is from about 0.5 mL to about 5 mL.

24. The unit liquid pharmaceutical formulation of claim 23 , wherein the volume is pre-loaded in a reservoir of a medical device.

25. The unit liquid pharmaceutical formulation of claim 24 , wherein the medical device is selected from the group consisting of a needle and syringe set, an autoinjector, a single use fixed dose injection pen, a multiuse fixed dose injection pen, a single use variable dose injection pen, and a multiuse variable dose injection pen.

26. The unit liquid pharmaceutical formulation of claim 2 , wherein the volume of the unit liquid pharmaceutical formulation is about 2 mL, about 1.5 mL, or about 1.0 mL.

27. The unit liquid pharmaceutical formulation of claim 26 , wherein the volume is pre-loaded in a reservoir of a medical device.

28. The unit liquid pharmaceutical formulation of claim 27 , wherein the medical device is selected from the group consisting of a needle and syringe set, an autoinjector, a single use fixed dose injection pen, a multiuse fixed dose injection pen, a single use variable dose injection pen, and a multiuse variable dose injection pen.

29. The unit liquid pharmaceutical formulation of claim 2 , wherein the volume of the unit liquid pharmaceutical formulation is about 0.5 mL.

30. The unit liquid pharmaceutical formulation of claim 29 , wherein the volume is pre-loaded in a reservoir of a medical device.

31. The unit liquid pharmaceutical formulation of claim 30 , wherein the medical device is selected from the group consisting of a needle and syringe set, an autoinjector, a single use fixed dose injection pen, a multiuse fixed dose injection pen, a single use variable dose injection pen, and a multiuse variable dose injection pen.

32. The unit liquid pharmaceutical formulation of claim 2 , wherein the volume of the unit liquid pharmaceutical formulation is from about 0.5 mL to about 5 mL.

33. The unit liquid pharmaceutical formulation of claim 32 , wherein the volume is pre-loaded in a reservoir of a medical device.

34. The unit liquid pharmaceutical formulation of claim 33 , wherein the medical device is selected from the group consisting of a needle and syringe set, an autoinjector, a single use fixed dose injection pen, a multiuse fixed dose injection pen, a single use variable dose injection pen, and a multiuse variable dose injection pen.