Pharmaceutical compositions of furosemide 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 furosemide, or a pharmaceutically acceptable salt, hydrate or ester thereof and a cyclodextrin.
1. A pharmaceutical composition, comprising:
from about 15 mg/mL to about 40 mg/mL furosemide, or a pharmaceutically acceptable salt thereof;
from about 10% to about 40% by weight of a sulfobutyl ether derivative of a β-cyclodextrin;
about 25 mM of a buffer comprising tris(hydroxymethyl)aminomethane;
optionally a pH adjusting agent; and
water;
wherein the pharmaceutical composition has a pH from about 7.0 to about 8.5.
2. A pharmaceutical composition, comprising:
about 20 mg/mL to about 40 mg/mL furosemide;
from about 10% to about 40% by weight of a sulfobutyl ether derivative of β-cyclodextrin;
about 25 mM of a buffer comprising tris(hydroxymethyl)aminomethane; and
water;
wherein the pharmaceutical composition has a pH of from about 7.0 to about 8.5.
3. The pharmaceutical composition of claim 2 , wherein the sulfobutyl ether derivative of β-cyclodextrin is captisol.
4. The pharmaceutical composition of claim 2 , wherein the pH value of the pharmaceutical composition is from about 7.2 to about 7.6.
5. The pharmaceutical composition of claim 2 , wherein the sulfobutyl ether derivative of β-cyclodextrin is present in an amount of from about 20% to about 30% by weight.
6. The pharmaceutical composition of claim 2 , wherein the sulfobutyl ether derivative of β-cyclodextrin is present in an amount of about 30% by weight.
7. A pharmaceutical composition, comprising:
from about 40 mM to about 160 mM of a diuretic selected from the group consisting of 4-chloro-2-((furan-2-ylmethyl)amino)-5-sulfamoylbenzoic acid, a pharmaceutically acceptable salt thereof, and a mixture thereof;
from about 45 mM to about 190 mM of a sulfobutyl ether derivative of β-cyclodextrin;
about 25 mM of a buffer comprising tris(hydroxymethyl)aminomethane; and
water; wherein the pharmaceutical composition has a pH value from about 7.0 to about 8.5.
8. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition comprises from about 120 mM to about 160 mM of a sulfobutyl ether derivative of β-cyclodextrin.
9. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition comprises from about 135 mM to about 145 mM of a sulfobutyl ether derivative of β-cyclodextrin.
10. The pharmaceutical composition of claim 7 , wherein the sulfobutyl ether derivative of β-cyclodextrin is sulfobutyl ether beta-cyclodextrin sodium.
11. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition comprises from about 80 mM to about 100 mM of the diuretic.
12. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition comprises about 91 mM of the diuretic.
13. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition has a pH of from about 7.0 to about 8.0.
14. The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition has a pH of about 7.4.
15. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition contains at least 50% (w/w) water.
16. The pharmaceutical composition of claim 7 , wherein less than 1% of the diuretic degrades upon storage of the pharmaceutical composition at 40° C. for 29 days.
17. The pharmaceutical composition of claim 7 , wherein less than 1% of the diuretic degrades upon storage of the pharmaceutical composition at 25° C. for 24 months.
18. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition comprises:
from 40 mM to 160 mM of a diuretic selected from the group consisting of 4-chloro-2-((furan-2-ylmethyl)amino)-5-sulfamoylbenzoic acid, a pharmaceutically acceptable salt thereof, and a mixture thereof;
from about 45 mM to about 190 mM of a sulfobutyl ether derivative of β-cyclodextrin;
about 25 mM of a buffer comprising tris(hydroxymethyl)aminomethane;
optionally a pH adjusting agent; and
water;
wherein the pharmaceutical composition has a pH value from about 7.0 to about 8.5.
19. The pharmaceutical composition of claim 18 , wherein the sulfobutyl ether derivative of β-cyclodextrin is present at a concentration of from about 135 mM to about 145 mM in the pharmaceutical composition.
20. The pharmaceutical composition of claim 18 , wherein the sulfobutyl ether derivative of β-cyclodextrin is sulfobutyl ether beta-cyclodextrin sodium.
21. The pharmaceutical composition of claim 19 , wherein the sulfobutyl ether derivative of β-cyclodextrin is sulfobutyl ether beta-cyclodextrin sodium.
22. The pharmaceutical composition of claim 18 , wherein the diuretic is present at a concentration of from about 80 mM to about 100 mM in the pharmaceutical composition.
23. The pharmaceutical composition of claim 21 , wherein the diuretic is present at a concentration of from about 80 mM to about 100 mM in the pharmaceutical composition.
24. The pharmaceutical composition of claim 18 , wherein the diuretic is present at a concentration of about 91 mM in the pharmaceutical composition.
25. The pharmaceutical composition of claim 21 , wherein the diuretic is present at a concentration of about 91 mM in the pharmaceutical composition.
26. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition has a pH of about 7.4.
27. The pharmaceutical composition of claim 25 , wherein the pharmaceutical composition has a pH of about 7.4.
28. A method of treating a condition selected from edema, heart failure, kidney disease, or liver disease, or symptoms thereof, comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 2 to treat the condition.