Stabilized liquid formulations containing picosulfate

Abstract

Stable liquid formulations containing picosulfate and magnesium citrate are provided. The formulations are useful to treat constipation or for the clearance of the bowel prior to X-ray examination, endoscopy or surgery.

What is claimed is: 
     
         1 . A liquid formulation comprising:
 picosulfate; magnesium citrate, and an antioxidant.   
     
     
         2 . The liquid formulation of  claim 1 , wherein the picosulfate is sodium picosulfate. 
     
     
         3 . The liquid formulation of  claim 1 , wherein the picosulfate is present in the formulation at a concentration in the range from about 0.10 mM to about 0.15 mM. 
     
     
         4 . The liquid formulation  claim 3 , wherein the picosulfate is present in the formulation at a concentration in the range from about 0.12 mM to about 0.14 mM. 
     
     
         5 . The liquid formulation of  claim 1 , wherein the antioxidant is chosen from ascorbic acid or a salt or ester thereof, butylated hydroxyanisole, butylated hydroxytoluene, histidine, D-mannose, propionic acid, potassium metabisulfite, propyl gallate, sodium metabisulfite, sodium sulfite, sodium thiosulfate, sulfur dioxide, and α-tocopherol. 
     
     
         6 . The liquid formulation of  claim 1 , wherein the antioxidant is chosen from ascorbic acid, sodium ascorbate, sodium metabisulfite, potassium metabisulfite, sodium sulfite, sodium thiosulfate, and sulfur dioxide. 
     
     
         7 . The liquid formulation of  claim 1 , wherein the antioxidant is sodium metabisulfite. 
     
     
         8 . The liquid formulation of  claim 1 , wherein the antioxidant is chosen from butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, and α-tocopherol. 
     
     
         9 . The liquid formulation of  claim 1 , wherein the antioxidant is present in the formulation at a concentration in the range from about 0.002 M to about 0.1 M. 
     
     
         10 . The liquid formulation of  claim 9 , wherein the antioxidant is present in the formulation at a concentration in the range from about 0.005 M to about 0.02 M. 
     
     
         11 . The liquid formulation of  claim 1 , wherein the magnesium citrate comprises magnesium and citrate in a molar ratio in the range from about 1:1 to about 1.5:1. 
     
     
         12 . The liquid formulation of  claim 11 , wherein the magnesium citrate comprises magnesium and citrate in a molar ratio of about 1.4:1. 
     
     
         13 . The liquid formulation of  claim 1 , wherein the magnesium citrate is formed from magnesium oxide and citric acid. 
     
     
         14 . The liquid formulation of  claim 1 , wherein the magnesium citrate is present in the formulation at a concentration of magnesium in the range from about 0.2 M to about 0.8 M. 
     
     
         15 . The liquid formulation of  claim 14 , wherein the magnesium citrate is present in the formulation at a concentration of magnesium in the range from about 0.5 M to about 0.6 M. 
     
     
         16 . The liquid formulation of  claim 1 , further comprising a carboxylic acid. 
     
     
         17 . The liquid formulation of  claim 16 , wherein the carboxylic acid is chosen from acetic acid, arginine, ascorbic acid, asparagine, aspartic acid, cysteine, fumaric acid, formic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, glycolic acid, histidine, lactic acid, lysine, maleic acid, malic acid, malonic acid, methionine, oxalic acid, propionic acid, serine, succinic acid, tartaric acid, threonine, and tyrosine. 
     
     
         18 . The liquid formulation of  claim 17 , wherein the carboxylic acid is malic acid, malonic acid or gluconic acid. 
     
     
         19 . The liquid formulation of  claim 16 , comprising the carboxylic acid at a concentration in the range from about 0.01 M to about 5 M. 
     
     
         20 . The liquid formulation of  claim 19 , comprising the carboxylic acid at a concentration in the range from about 0.1 M to about 1 M. 
     
     
         21 . The liquid formulation of  claim 1 , further comprising a water soluble anionic polymer. 
     
     
         22 . The liquid formulation of  claim 21 , wherein the water soluble anionic polymer is chosen from alginic acid, carboxymethylcellulose, carrageenans, polyacrylic acid and copolymers thereof, and xanthan gum. 
     
     
         23 . The liquid formulation of  claim 21 , comprising the water soluble anionic polymer at a concentration in the range from about 0.5 g/L to about 25 g/L. 
     
     
         24 . The liquid formulation of  claim 1 , further comprising a preservative agent chosen from methyl paraben, propyl paraben, sodium benzoate and potassium benzoate. 
     
     
         25 . The liquid formulation of  claim 1 , further comprising a chelating agent. 
     
     
         26 . The liquid formulation of  claim 1 , wherein the pH of the formulation is in the range from about 4.5 to about 5.2. 
     
     
         27 . The liquid formulation of  claim 26 , wherein the pH of the formulation is in the range from about 4.7 to about 4.9. 
     
     
         28 . The liquid formulation of  claim 27 , wherein the pH of the formulation is about 4.9. 
     
     
         29 . The liquid formulation of  claim 1 , wherein, when stored for 1 year at a temperature of about 25° C. and about 60% relative humidity, the formulation forms less than about 1.5% of Picosulfate Benzyl Alcohol and less than about 0.2% of Compound RRT 1.35 as measured by HPLC analysis area percentage compared to sodium picosulfate. 
     
     
         30 . The liquid formulation of  claim 1 , wherein, when stored for 1 year at a temperature of about 25° C. and about 60% relative humidity, the formulation forms less than about 1.5% of Picosulfate Related Compound A, less than about 1.5% of Picosulfate Benzyl Alcohol, less than about 0.2% of Compound RRT 1.35, and less than about 0.2% of Compound RRT 1.94 as measured by HPLC analysis area percentage compared to sodium picosulfate. 
     
     
         31 . The liquid formulation of  claim 1 , wherein, when stored for 1 year at a temperature of about 25° C. and about 60% relative humidity, the formulation forms less than about 1% of Picosulfate Related Compound A, less than about 1.3% of Picosulfate Benzyl Alcohol, less than about 0.2% of Compound RRT 1.35, and less than about 0.2% of Compound RRT 1.94 as measured by HPLC analysis area percentage compared to sodium picosulfate.