Spironolactone aqueous compositions
Disclosed herein is a stable, ready-to-use liquid formulation comprising spironolactone and its method of use.
1. A method of treating an adult patient having heart failure, hypertension, or edema, said method comprising:
administering to the patient in need thereof a ready-to-use liquid formulation comprising:
micronized spironolactone in an amount of about 5 mg/mL;
xanthan gum in an amount to provide a formulation viscosity of from 100 cP to 300 cP,
glycerin in an amount of from 18 mg/mL to 24 mg/mL;
a sufficient amount of a citrate buffer to maintain a pH of the formulation from 4.5 to 5.5
and
a water vehicle.
2. The method of claim 1 , wherein the micronized spironolactone has a median volume particle size of not more than about 9.6 μm.
3. The method of claim 1 , wherein the micronized spironolactone has a median volume particle size of about 3.6 μm to about 9.6 μm.
4. The method of claim 1 , wherein the xanthan gum is present in an amount of from 1.3 mg/mL to 3.6 mg/mL.
5. The method of claim 1 , wherein the xanthan gum is present in an amount of from 1.8 mg/mL to 3.6 mg/mL.
6. The method of claim 1 , wherein the glycerin is present in an amount of from 18 mg/mL to 22 mg/mL.
7. The method of claim 1 , wherein the citrate buffer is present in an amount of from about 10 mM to about 100 mM.
8. The method of claim 1 , wherein the ready-to-use liquid formulation has a formulation viscosity that ranges from 120 cP to 170 cP.
9. The method of claim 1 , wherein the ready-to-use liquid formulation has a formulation viscosity that ranges from 150 cP to 170 cP.
10. The method of claim 1 , which further comprises administering to the adult patient having heart failure about 4 mL of the ready-to-use liquid formulation once daily or once every other day, wherein said patient has a serum potassium level of ≤5.0 mEq/L and an estimated glomular filtration rate >50 mL/min/1.73 m 2 .
11. The method of claim 1 , which further comprises administering to the adult patient having heart failure about 7.5 mL of the ready-to-use liquid formulation once daily or once every other day, wherein said patient has a serum potassium level of ≤5.0 mEq/L and an estimated glomular filtration rate >50 mL/min/1.73 m 2 .
12. A method of treating an adult patient having heart failure, hypertension, or edema, said method comprising:
administering to the patient in need thereof a ready-to-use liquid formulation comprising:
micronized spironolactone in an amount of about 5 mg/mL;
xanthan gum in an amount to provide a formulation viscosity of from 100 cP to 300 cP,
a dispersing agent consisting of glycerin in an amount of from 18 mg/mL to 24 mg/mL,
a sufficient amount of a citrate buffer to maintain a pH of the formulation from 4.5 to 5.5 and
a water vehicle.
13. The method of claim 12 , wherein the micronized spironolactone has a median volume particle size of not more than about 9.6 μm.
14. The method of claim 12 , wherein the spironolactone has a median volume particle size of about 3.6 μm to about 9.6 μm.
15. The method of claim 12 , wherein the xanthan gum is present in an amount of from 1.3 mg/mL to 3.6 mg/mL.
16. The method of claim 12 , wherein the xanthan gum is present in an amount of from 1.8 mg/mL to 3.6 mg/mL.
17. The method of claim 12 , wherein the glycerin is present in an amount of from 18 mg/mL to 22 mg/mL.
18. The method of claim 12 , wherein the citrate buffer is present in an amount of from about 10 mM to about 100 mM.
19. The method of claim 12 , wherein the ready-to-use liquid formulation has a viscosity that ranges from 120 cP to 170 cP.
20. The method of claim 12 , wherein the ready-to-use liquid formulation has a formulation viscosity that ranges from 150 cP to 170 cP.
21. The method of claim 12 , which further comprises administering to the adult patient having heart failure about 4 mL of the ready-to-use liquid formulation once daily or once every other day, wherein said patient has a serum potassium level of ≤5.0 mEq/L and an estimated glomular filtration rate >50 mL/min/1.73 m 2 .
22. The method of claim 12 , which further comprises administering to the adult patient having heart failure about 7.5 mL of the ready-to-use liquid formulation once daily or once every other day, wherein said patient has a serum potassium level of ≤5.0 mEq/L and an estimated glomular filtration rate >50 mL/min/1.73 m 2 .
23. The method of claim 1 , which further comprises administering to the adult patient having heart failure about 2 mL of the ready-to-use liquid formulation once daily or once every other day wherein said patient has a serum potassium level of ≤5.0 mEq/L and an estimated glomular filtration rate (eGFR) between 30 to 50 mL/min/1.73 m 2 .
24. The method of claim 12 , which further comprises administering to the adult patient having heart failure about 2 mL of the ready-to-use liquid formulation once daily or once every other day wherein said patient has a serum potassium level of ≤5.0 mEq/L and an estimated glomular filtration rate (eGFR) between 30 to 50 mL/min/1.73 m 2 .
25. The method of claim 1 , which further comprises administering to the adult patient having hypertension about 4 mL of the ready-to-use liquid formulation once daily in a single or a divided dose, wherein the hypertension is essential hypertension.
26. The method of claim 12 , which further comprises administering to the adult patient having hypertension about 4 mL of the ready-to-use liquid formulation once daily in a single or a divided dose, wherein the hypertension is essential hypertension.
27. The method of claim 1 , which further comprises administering to the adult patient having an essential hypertension about 15 mL of the ready-to-use liquid formulation once daily in a single or a divided dose, wherein the hypertension is essential hypertension.
28. The method of claim 12 , which further comprises administering to the adult patient having an essential hypertension about 15 mL of the ready-to-use liquid formulation once daily in a single or a divided dose, wherein the hypertension is essential hypertension.
29. The method of claim 1 , which further comprises administering to the adult patient having edema about 15 mL of the ready-to-use liquid formulation once daily.
30. The method of claim 12 , which further comprises administering to the adult patient having edema about 15 mL of the ready-to-use liquid formulation once daily.