Spironolactone Aqueous Compositions

Abstract

Disclosed herein is a stable, ready-to-use liquid formulation comprising spironolactone and its method of use.

We claim: 
     
         1 . A ready-to-use liquid formulation, comprising:
 micronized spironolactone in an amount of about 5 mg/mL;   one or more pharmaceutically acceptable excipients comprising
 a hydrocolloid in an amount to provide a formulation viscosity of from 100 cP to 300 cP, and 
 glycerin in an amount of from 18 mg/mL to 24 mg/mL; and 
   a water vehicle.   
     
     
         2 . The ready-to-use liquid formulation of  claim 1 , wherein the micronized spironolactone has a median volume particle size of not more than about 9.6 μm. 
     
     
         3 . The ready-to-use liquid formulation 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 ready-to-use liquid formulation of  claim 1 , wherein the hydrocolloid comprises xanthan gum, methylcellulose, magnesium aluminum silicate, or a combination thereof. 
     
     
         5 . The ready-to-use liquid formulation of  claim 1 , wherein the hydrocolloid comprises from 1.3 mg/mL to 3.6 mg/mL xanthan gum. 
     
     
         6 . The ready-to-use liquid formulation of  claim 1 , wherein the glycerin is present in an amount of from 18 mg/mL to 22 mg/mL. 
     
     
         7 . The ready-to-use liquid formulation of  claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a buffer and wherein the pH of the formulation ranges from 4.5 to 5.5. 
     
     
         8 . The ready-to-use liquid formulation of  claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a buffer and wherein the pH of the formulation ranges from 4.8 to 5.2. 
     
     
         9 . The ready-to-use liquid formulation of  claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a buffer in an amount of about 10 mM to about 100 mM; wherein the pH of the formulation ranges from 4.8 to 5.2; and wherein the buffer is selected from acetate, aconitate, glutarate, glutamate, malate, succinate, tartrate, citrate, and phosphate. 
     
     
         10 . The ready-to-use liquid formulation of  claim 1 , wherein the formulation viscosity ranges from 130 cP to 170 cP. 
     
     
         11 . The ready-to-use liquid formulation of  claim 1 , wherein the spironolactone content is 100±10% of labeled content when stored under 25±° C. and 40% relative humidity for 12-months. 
     
     
         12 . A method of treating an adult patient having heart failure, hypertension, or edema, said method comprising administering to the patient in need thereof the ready-to-use liquid formulation of  claim 1 . 
     
     
         13 . 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 . 
     
     
         14 . 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 . 
     
     
         15 . 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 . 
     
     
         16 . 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. 
     
     
         17 . 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. 
     
     
         18 . 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.