Pharmaceutical composition of pemetrexed

Abstract

The present invention relates to pharmaceutical composition comprising pemetrexed, a ready to use injection comprising pemetrexed. Liquid composition of pemetrexed comprises head space oxygen less than 5%, dissolved oxygen less than 2ppm and individual impurity level less than 0.2%.

1 - 9 . (canceled) 
     
     
         10 . A liquid composition of pemetrexed comprising head space oxygen less than 5% with dissolved oxygen less than 2 parts per million (ppm) and individual impurity level in the final product less than 0.5%. 
     
     
         11 . The liquid composition of pemetrexed of claim  1 , wherein said composition comprises 5 to 100 mg/mL of pemetrexed or its pharmaceutically acceptable salts, at least one antioxidant and pharmaceutically acceptable excipients. 
     
     
         12 . The liquid composition of pemetrexed of  claim 11 , wherein the amount of said antioxidant in said composition is 10 mg/mL or less. 
     
     
         13 . The liquid composition of pemetrexed of  claim 11 , wherein said antioxidant comprises monothioglycerol, L-cysteine, thioglycolic acid or a combination thereof. 
     
     
         14 . The liquid composition of pemetrexed of  claim 11 , wherein said antioxidant comprises acetyl cysteine, butylated hydroxy toluene, butylated hydroxy anisole, DL-tocopherol, sodium metabisulfite, sodium formaldehyde sulfoxylate, ethylenediamine-tetraacetic acid (EDTA) or its derivatives, methionine, ascorbic acid, citric acid or its pharmaceutically acceptable salt, sodium sulfite or its derivative, or a combination thereof. 
     
     
         15 . The liquid composition of pemetrexed of  claim 10 , wherein said composition further comprises a pharmaceutically acceptable excipient. 
     
     
         16 . The liquid composition of pemetrexed of  claim 15 , wherein said pharmaceutically acceptable excipient comprises an osmolarity adjusting agent, a stabilizing agent, an optionally chelating agent, a pH adjusting agent, an optionally buffering agent, a vehicle, or a combination thereof. 
     
     
         17 . The liquid composition of pemetrexed of  claim 10 , wherein said composition is optionally prepared using a process of terminal sterilization. 
     
     
         18 . The liquid composition of pemetrexed of  claim 17 , wherein said terminal sterilization is steam sterilization with F 0  value of from 1 to 30 min. 
     
     
         19 . A process for preparing a liquid composition of pemetrexed comprising:
 a. preparing a solution of excipients and pemetrexed under conditions to maintain dissolved oxygen level of 2 ppm or less;   b. filtering and filling a vial with the solution of step (a) and maintaining head space oxygen of less than 5%; and   c. sterilizing said solution of said step (b) by steam sterilization with F 0  value of from 1 to 30 min.   
     
     
         20 . A liquid pharmaceutical composition of comprising:
 about 10 mg/mL of pemetrexed;   head space oxygen of less than 5% with dissolved oxygen of less than 2 ppm; and   individual impurity level of less than 0.5%.   
     
     
         21 . The liquid pharmaceutical composition of  claim 20  further comprising cysteine as an antioxidant. 
     
     
         22 . The liquid pharmaceutical composition of  claim 21 , wherein the amount of said cysteine is about 2.5 mg/mL.