Concentrated liquid pharmaceutical formulations of furosemide and methods of administering the same
Disclosed herein, in part, are liquid pharmaceutical formulations comprising furosemide or a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable excipients, and a pharmaceutically acceptable buffer. Methods of treating congestion, edema, fluid overload, or hypertension in a patient in need thereof are also provided.
1 . A liquid pharmaceutical formulation comprising:
(i) furosemide, or a pharmaceutically acceptable salt thereof;
(ii) one or more pharmaceutically acceptable excipients comprising benzyl alcohol; and
(iii) a pharmaceutically acceptable buffer comprising tromethamine or a pharmaceutically acceptable salt thereof in a concentration from about 25 mM to about 100 mM,
wherein the concentration of furosemide in the liquid pharmaceutical formulation is from about 40 mg/mL to about 250 mg/mL.
2 . The liquid pharmaceutical formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients is selected from the group consisting of ethanol, glycerin, N-methyl-pyrrolidone (NMP), sodium chloride, a polyethylene glycol (PEG), propylene glycol, a polysorbate, a polyvinylpyrrolidone (PVP), a cyclodextrin, and any combination thereof.
3 . The liquid pharmaceutical formulation of claim 1 , wherein the amount of the one or more pharmaceutically acceptable excipients in the liquid pharmaceutical formulation is from about 0.1% (w/w) to about 30% (w/w).
4 . A liquid pharmaceutical formulation comprising:
(i) furosemide, or a pharmaceutically acceptable salt thereof;
(ii) benzyl alcohol; and tromethamine or a pharmaceutically acceptable salt thereof in a concentration from about 25 mM to about 150 mM, wherein the concentration of furosemide in the liquid pharmaceutical formulation is from about 60 mg/mL to about 250 mg/mL.
5 . The liquid pharmaceutical formulation of 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 of claim 4 , wherein the amount of benzyl alcohol in the liquid pharmaceutical formulation is from about 0.5% (w/w) to about 5% (w/w).
7 . The liquid pharmaceutical formulation of claim 4 , wherein the concentration of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulation is from about 25 mM to about 75 mM.
8 . A liquid pharmaceutical formulation, comprising:
(i) 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 comprising benzyl alcohol; and
(iii) from about 25 mM to about 100 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 40 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.
9 . A liquid pharmaceutical formulation of claim 8 , comprising: from about 0.1% (w/w) to about 10% (w/w) benzyl alcohol.
10 . The liquid pharmaceutical formulation of claim 8 , wherein the amount of benzyl alcohol in the liquid pharmaceutical formulation is from about 0.5% (w/w) to about 5% (w/w).
11 . The liquid pharmaceutical formulation of claim 1 , wherein the amount of tromethamine or a pharmaceutically acceptable salt thereof in the liquid pharmaceutical formulation is from about 25 mM to about 75 mM.
12 . The liquid pharmaceutical formulation of claim 1 , wherein the pH of the liquid pharmaceutical formulation is from about 6.5 to about 8.5.
13 . The liquid pharmaceutical formulation of claim 1 , wherein the pH of the liquid pharmaceutical formulation is from about 7 to about 8.
14 . A method of treating congestion, edema, fluid overload, or hypertension in a patient in need thereof, the method comprising administering to the patient the liquid pharmaceutical formulation of claim 1 .
15 . The method of claim 14 , wherein the liquid pharmaceutical formulation is administered to the patient by subcutaneous injection or subcutaneous infusion.
16 . The method of claim 15 , wherein the liquid pharmaceutical formulation is administered to the patient by subcutaneous infusion using an on-body, subcutaneous delivery system.
17 . The method of claim 16 , wherein the on-body, subcutaneous delivery system is a pump device.
18 . A kit for the treatment of congestion, edema, fluid overload, or hypertension comprising a liquid pharmaceutical formulation of claim 1 ; and instructions for treating the congestion, edema, fluid overload, or hypertension.
19 . The kit of claim 18 , comprising one, two, three or more units of the liquid pharmaceutical formulation.
20 . The kit of claim 18 , further comprising an on-body, subcutaneous delivery system.