Stable ready-to-use carmustine pharmaceutical composition

Abstract

The present invention relates to a ready-to-use solution of carmustine that does not require dissolution or dilution of the carmustine prior to addition to saline and dextrose parenteral solutions. In particular, the invention relates to a stable liquid pharmaceutical composition containing carmustine in the form of ready-to-use solution and method for preparing the same.

1 . A liquid, ready-to-use parenteral pharmaceutical composition of carmustine dissolved in polysorbate as the sole solvent, wherein the pharmaceutical composition has a concentration of about 2 mg/mL to about 500 mg/mL of carmustine and wherein the liquid ready-to-use parenteral pharmaceutical composition is water free. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the polysorbate is selected from polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 and mixtures thereof. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the polysorbate is super refined polysorbate 80 with a peroxide value below 10 meq 02/kg. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition, after storage at 2-8° C. for 3 months, contains at least 90% by weight of the initial amount of carmustine. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition is admixed with 500 mL of 0.9% sodium chloride injection or 5% dextrose injection to form an administrable solution prior to administration to a patient. 
     
     
         6 . The pharmaceutical composition according to  claim 5 , wherein the administrable solution has a concentration of about 0.2 mg/mL of carmustine. 
     
     
         7 . A method for administering carmustine comprising:
 (a) adding the liquid, ready-to-use parenteral pharmaceutical composition of  claim 1  to 500 mL of 0.9% sodium chloride solution for injection or 5% dextrose solution for injection to form an administrable solution, wherein the pharmaceutical composition consists of carmustine dissolved in polysorbate 80 as the sole solvent, wherein the pharmaceutical composition has concentration of about 100 mg/mL of carmustine and the pharmaceutical composition has been stored at 2 to 8° C. in a sealed vial, and   (b) parenterally administering the administrable solution to a patient in need thereof.   
     
     
         8 . The pharmaceutical composition according to  claim 3 , wherein the polysorbate is super refined polysorbate 80 with a peroxide value about 0.5 meq 02/kg. 
     
     
         9 . The pharmaceutical composition according to  claim 3 , wherein the polysorbate is super refined polysorbate 80 with a peroxide value about 0.2 meq 02/kg. 
     
     
         10 . A liquid, ready-to-use parenteral pharmaceutical composition of carmustine dissolved in polysorbate as the sole solvent, wherein the pharmaceutical composition has a concentration of about 2 mg/mL to about 500 mg/mL of carmustine; the polysorbate is super refined polysorbate with a peroxide value below 10 meq 02/kg, the liquid ready-to-use parenteral pharmaceutical composition is water free, free of visible particles and is stored in a container that is free of polyvinyl chloride and free of di-2-ethylhexylphthalate. 
     
     
         11 . The pharmaceutical composition according to  claim 10 , wherein the polysorbate is selected from polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 and mixtures thereof. 
     
     
         12 . The pharmaceutical composition according to  claim 10 , wherein the polysorbate is super refined polysorbate with a peroxide value about 0.5 meq 02/kg. 
     
     
         13 . The pharmaceutical composition according to  claim 12 , wherein the polysorbate is super refined polysorbate with a peroxide value about 0.2 meq 02/kg. 
     
     
         14 . The pharmaceutical composition according to  claim 10 , wherein the pharmaceutical composition, after storage at 2-8° C. for 3 months, contains at least 90% by weight of the initial amount of carmustine. 
     
     
         15 . The pharmaceutical composition according to  claim 10  wherein the composition is stored in a vial with a head space within the vial comprising not more than 6% oxygen. 
     
     
         16 . The pharmaceutical composition according to  claim 10 , wherein the pharmaceutical composition is admixed with 500 mL of 0.9% sodium chloride injection or 5% dextrose injection to form an administrable solution prior to administration to a patient. 
     
     
         17 . A method for administering carmustine comprising:
 (a) adding the liquid, ready-to-use parenteral pharmaceutical composition of  claim 10  to 500 mL of 0.9% sodium chloride solution for injection or 5% dextrose solution for injection to form an administrable solution, wherein the pharmaceutical composition has concentration of about 100 mg/mL of carmustine and the pharmaceutical composition has been stored at 2 to 8° C. in a sealed vial, and   (b) parenterally administering the administrable solution to a patient in need thereof.   
     
     
         18 . A liquid, ready-to-use parenteral pharmaceutical composition of carmustine dissolved in super refined polysorbate 80 with a peroxide value below 10 meq 02/kg as the sole solvent, wherein the pharmaceutical composition has a concentration of about 100 mg/mL, the liquid ready-to-use parenteral pharmaceutical composition is water free, free of visible particles and is stored in a container with a head space containing no more than 6% oxygen and wherein the container is free of polyvinyl chloride and free of di-2-ethylhexylphthalate. 
     
     
         19 . The pharmaceutical composition as defined in  claim 18  wherein the polysorbate 80 has a peroxide value about 0.2 meq 02/kg to about 0.5 meq 02/kg.