Liquid Formulations of Bendamustine

Abstract

Stable liquid formulations of bendamustine, and pharmaceutically acceptable salts thereof, and polar aprotic solvents, are described.

What is claimed: 
     
         1 . A method of treating cancer comprising
 providing a non-aqueous liquid, pharmaceutical formulation comprising bendamustine, or a pharmaceutically acceptable salt thereof, and a polar aprotic solvent, wherein said formulation is stable following storage at a temperature of about 5° C. for a time period of from about 30 to about 365 days;   diluting the non-aqueous liquid, pharmaceutical formulation with a pharmaceutically acceptable injectable diluent to form an injectable pharmaceutical preparation;   administering the injectable pharmaceutical preparation to a patient in need of treatment for cancer.   
     
     
         2 . The method of  claim 1 , wherein the non-aqueous liquid, pharmaceutical formulation comprises the polar aprotic solvent dimethylacetamide. 
     
     
         3 . The method of  claim 2 , wherein the non-aqueous liquid, pharmaceutical formulation comprises the polar aprotic solvent dimethylacetamide and further comprises the nonaqueous polar protic solvent propylene glycol 
     
     
         4 . The method of  claim 3 , wherein the non-aqueous liquid, pharmaceutical formulation comprises about 66% (v/v) of the dimethylacetamide and about 34% (v/v) of the propylene glycol. 
     
     
         5 . The method of  claim 1 , wherein the non-aqueous liquid, pharmaceutical formulation comprises from about 5 mg/ml to about 120 mg/mL of bendamustine, or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The method of  claim 1 , wherein the non-aqueous liquid, pharmaceutical formulation comprises about 100 mg/mL of bendamustine, or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The method of  claim 1 , wherein the pharmaceutically acceptable injectable diluent is 0.9% sodium chloride. 
     
     
         8 . The method of  claim 1 , wherein the cancer is chronic lymphocytic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or breast cancer. 
     
     
         9 . The method of  claim 8 , wherein the cancer is chronic lymphocytic leukemia or non-Hodgkin's lymphoma. 
     
     
         10 . The method of  claim 1 , wherein the polar aprotic solvent is 1-methyl-2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethylacetamide, dimethyl sulfoxide, acetone, tetrahydrofuran, 1,4-dioxane, acetonitrile, dimethyl formamide, propylene carbonate, or a mixture thereof. 
     
     
         11 . The method of  claim 10 , wherein the non-aqueous liquid, pharmaceutical formulation further comprises a non-aqueous polar protic solvent. 
     
     
         12 . The method of  claim 11 , wherein the non-aqueous polar protic solvent is an alcohol, a polyalkylene glycol, an amide, or a mixture thereof. 
     
     
         13 . The method of  claim 12 , wherein the non-aqueous polar protic solvent is ethylene glycol, propylene glycol, butylene glycol, or a mixture thereof. 
     
     
         14 . The method of  claim 1 , wherein the non-aqueous liquid, pharmaceutical formulation further comprises an antioxidant, a surfactant, a lipid, a filler, an organic acid, a hydrophilic polymer, a complexing agent, a preservative, or a combination thereof.