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 . An anhydrous, liquid, pharmaceutical formulation of bendamustine, or a pharmaceutically acceptable salt thereof, comprising 1.5% or less of PG-1, PG-2, or a combination thereof 
       
         
           
           
               
               
           
         
         as determined by HPLC analysis. 
       
     
     
         2 . The anhydrous, liquid, pharmaceutical formulation of  claim 1 , wherein the analysis is performed after about 1 year of storage. 
     
     
         3 . The anhydrous, liquid, pharmaceutical formulation of  claim 1 , wherein the analysis is performed after about 1 year of storage at about 5° C. 
     
     
         4 . The anhydrous, liquid, pharmaceutical formulation of  claim 1 , further comprising an alkylene glycol. 
     
     
         5 . The anhydrous, liquid, pharmaceutical formulation of  claim 4 , wherein the alkylene glycol is propylene glycol. 
     
     
         6 . The anhydrous, liquid, pharmaceutical formulation of  claim 1 , comprising at least about 90% of the amount of bendamustine present prior to storage of about 1 year, as determined by HPLC analysis. 
     
     
         7 . The anhydrous, liquid, pharmaceutical formulation of  claim 6 , wherein the storage is at about 5° C. 
     
     
         8 . The anhydrous, liquid, pharmaceutical formulation of  claim 1 , comprising at least about 90% of the amount of bendamustine present prior to storage of about 180 days, as determined by HPLC analysis. 
     
     
         9 . The anhydrous, liquid, pharmaceutical formulation of  claim 8 , wherein the storage is at about 5° C. 
     
     
         10 . The anhydrous, liquid, pharmaceutical formulation of  claim 1 , comprising at least about 90% of the amount of bendamustine present prior to storage of about 90 days, as determined by HPLC analysis. 
     
     
         11 . The anhydrous, liquid, pharmaceutical formulation of  claim 10 , wherein the storage is at about 5° C. 
     
     
         12 . The anhydrous, liquid, pharmaceutical formulation of  claim 1 , comprising at least about 90% of the amount of bendamustine present prior to storage of about 30 days, as determined by HPLC analysis. 
     
     
         13 . The anhydrous, liquid, pharmaceutical formulation of  claim 12 , wherein the storage is at about 5° C. 
     
     
         14 . The anhydrous, liquid, pharmaceutical formulation of  claim 1 , wherein the formulation is sterile. 
     
     
         15 . The anhydrous, liquid, pharmaceutical formulation of  claim 1 , comprising bendamustine at a concentration of about 5 mg/mL to about 200 mg/mL. 
     
     
         16 . An anhydrous, liquid, pharmaceutical formulation comprising bendamustine, or a pharmaceutically acceptable salt thereof, and propylene glycol, comprising about 1.5% or less of PG-1, PG-2, or a combination thereof 
       
         
           
           
               
               
           
         
         as determined by HPLC analysis. 
       
     
     
         17 . A method of treating cancer comprising
 providing the anhydrous, liquid, pharmaceutical formulation of  claim 1 ;   diluting the anhydrous, 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.   
     
     
         18 . The method of  claim 17 , wherein the cancer is chronic lymphocytic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or breast cancer. 
     
     
         19 . The method of  claim 17 , wherein the cancer is chronic lymphocytic leukemia or non-Hodgkin's lymphoma.