Liquid Formulations Of Bendamustine

Abstract

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

1 . A stable, non-aqueous, liquid formulation comprising from about 5 mg/mL to about 200 mg/mL of bendamustine or a pharmaceutically acceptable salt thereof and up to about 90% of a non-aqueous polar protic solvent. 
     
     
         2 . The liquid formulation of  claim 1 , further comprising an antioxidant. 
     
     
         3 . The liquid formulation of  claim 1 , wherein said formulation contains not less than about 95% of the amount of bendamustine present prior to exposure to storage conditions that include a temperature of about 5° C. and a time period of about 180 days. 
     
     
         4 . The liquid formulation of  claim 1 , wherein said non-aqueous polar protic solvent is: an alkyl alcohol selected from ethylene glycol, propylene glycol, butylene glycol, glycerin, TWEEN 20, TWEEN 40, TWEEN 80, and a cyclodextrin; a polyalkylene glycol selected from polyethylene glycol, polypropylene glycol, and polybutylene glycol; niacinamide; or a mixture thereof. 
     
     
         5 . The liquid formulation of  claim 4 , wherein said non-aqueous polar protic solvent comprises polyethylene glycol. 
     
     
         6 . The liquid formulation of  claim 5 , wherein said non-aqueous polar protic solvent is a mixture of polyethylene glycol and propylene glycol. 
     
     
         7 . The liquid formulation of  claim 6 , wherein said formulation comprises 1.5% or less of PG-1, PG-2, or a combination thereof 
       
         
           
           
               
               
           
         
       
       as determined by HPLC analysis, after about 1 year of storage at about 5° C. 
     
     
         8 . A method of treating cancer comprising:
 providing the stable, non-aqueous, liquid 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.   
     
     
         9 . The method of  claim 8 , wherein the cancer is chronic lymphocytic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or breast cancer. 
     
     
         10 . The method of  claim 9 , wherein the cancer is chronic lymphocytic leukemia or non-Hodgkin's lymphoma.