Pharmaceutical compositions of torsemide and uses thereof
A pharmaceutical composition and a method of administering the pharmaceutical composition to a patient suffering from edema, heart failure, kidney or liver disease or having symptoms thereof are disclosed. The pharmaceutical composition includes torsemide, or a pharmaceutically acceptable salt, hydrate or ester thereof and a cyclodextrin.
1. A pharmaceutical composition, comprising:
torsemide, or a pharmaceutically acceptable salt, hydrate or ester thereof;
from 20% to 40% by weight of a β-cyclodextrin;
a buffer comprising tris(hydroxymethyl)aminomethane; and
at least 55% (w/w) water;
wherein the molar ratio of β-cyclodextrin to torsemide is greater than 2; and
the pharmaceutical composition has a pH value from about 7.0 to about 7.8.
2. The pharmaceutical composition of claim 1 , wherein the β-cyclodextrin is a sulfobutyl ether derivative of β-cyclodextrin.
3. The pharmaceutical composition of claim 2 , wherein the sulfobutyl ether derivative of β-cyclodextrin is sulfobutyl ether beta-cyclodextrin sodium.
4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a pH value from about 7.2 to about 7.6.
5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a pH value of about 7.42.
6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition contains the torsemide in an amount of from about 10 mg/mL to about 20 mg/mL.
7. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition contains the β-cyclodextrin in an amount of from 20% to 30% by weight.
8. The pharmaceutical composition of claim 7 , wherein the water is present in an amount of at least 60% (w/w) of the pharmaceutical composition.
9. The pharmaceutical composition of claim 1 , wherein the molar ratio of β-cyclodextrin to torsemide is from 2:1 to about 3:1.
10. A pharmaceutical composition, comprising:
from about 14 mM to about 115 mM of a diuretic selected from the group consisting of N-(isopropylcarbamoyl)-4-(m-tolylamino)pyridine-3-sulfonamide, a pharmaceutically acceptable salt thereof, and a mixture of the foregoing;
from 90 mM to 140 mM of a sulfobutyl ether derivative of β-cyclodextrin;
a buffer comprising tris(hydroxymethyl)aminomethane; and
at least 60% (w/w) water; wherein the pharmaceutical composition has a pH value from about 7.0 to about 8.0.
11. The pharmaceutical composition of claim 10 , wherein the sulfobutyl ether derivative of β-cyclodextrin is sulfobutyl ether beta-cyclodextrin sodium.
12. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition comprises from about 25 mM to about 60 mM of the diuretic.
13. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition comprises from about 25 mM to about 30 mM of the diuretic.
14. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition comprises from about 55 mM to about 60 mM of the diuretic.
15. The pharmaceutical composition of claim 10 , wherein the buffer is present in an amount ranging from about 1% (w/w) to about 5% (w/w).
16. The pharmaceutical composition of claim 10 , wherein the buffer is present in an amount of about 2% (w/w).
17. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition has a pH of from about 7.2 to about 7.6.
18. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition has a pH of about 7.4.
19. The pharmaceutical composition of claim 10 , wherein less than 1% of the diuretic degrades upon storage of the pharmaceutical composition at 40° C. for 29 days.
20. A method of treating a patient suffering from a condition selected from edema, heart failure, kidney disease, or liver disease, or having a symptom of any of the foregoing, comprising administering to the patient in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 10 to treat the condition.
21. A pharmaceutical composition, comprising:
from about 14 mM to about 115 mM of a diuretic selected from the group consisting of N-(isopropylcarbamoyl)-4-(m-tolylamino)pyridine-3-sulfonamide, a pharmaceutically acceptable salt thereof, and a mixture of the foregoing;
from about 130 mM to about 150 mM of a sulfobutyl ether derivative of β-cyclodextrin;
a buffer comprising tris(hydroxymethyl)aminomethane; and
at least 55% (w/w) water; wherein the pharmaceutical composition has a pH value from about 7.0 to about 8.0.
22. The pharmaceutical composition of claim 21 , wherein the water is present in an amount of at least 60% (w/w) of the pharmaceutical composition.