Liquid formulations of fosaprepitant

Abstract

The present invention relates to liquid formulations of Fosaprepitant intended for parenteral administration. Further the invention also describes process for preparing such formulations.

1 - 8 . (canceled) 
     
     
         9 . A stable, liquid parenteral pharmaceutical formulation of fosaprepitant comprising
 (i) fosaprepitant dimeglumine from approximately 0.1% to 15% w/w based on the total weight of the formulation;   (ii) one or more chelating agents, wherein each are individually present from approximately 0.01% to approximately 5% w/w based on the total weight of the formulation;   (iii) one or more stabilizing agents;   (iv) one or more pH adjusting agents or buffering agents;   (v) one or more solvents; and optionally; and   (vi) other pharmaceutically acceptable excipients;   
       wherein the pH of the formulation ranges from 7 to 13. 
     
     
         10 . The stable, liquid parenteral pharmaceutical formulation of  claim 9 , wherein after storage at 2-8° C. for at least 1 month, the concentration of aprepitant is not more than 10%. 
     
     
         11 . The stable, liquid parenteral pharmaceutical formulation of  claim 9 , wherein chelating agents are selected from EDTA, DTPA, DOTA and salts thereof. 
     
     
         12 . The stable, liquid parenteral pharmaceutical formulation of  claim 9 , wherein one or more stabilizing agents selected from surfactants and cyclodextrins. 
     
     
         13 . The stable, liquid parenteral pharmaceutical formulation of  claim 9 , wherein the surfactant is selected from polysorbates, polyethylene glycol esters, sorbitan esters (e.g. Tweens), polyoxyethylated vegetable oil, polyethoxylated castor oil and sucrose fatty acid esters. 
     
     
         14 . The stable, liquid parenteral pharmaceutical formulation of  claim 12 , wherein the cyclodextrin is selected from α, β and γ-cyclodextrin and cyclodextrins modified with alkyl-, hydroxyalkyl-, dialkyl-, and sulfoalkyl-ether modified cyclodextrins such as methyl or hydroxypropyl β-cyclodextrins (HPβCD), sulfoalkylether-substituted beta-cyclodextrin and sulfobutylether-β-cyclodextrin (SBECD). 
     
     
         15 . The stable, liquid parenteral pharmaceutical formulation of  claim 12 , wherein pH adjusting agents and buffering agents are selected from phosphate buffer, citrate buffer, sodium carbonate, sodium bicarbonate, tartrate, benzoate, lactate, acetate, borate, glutaric acid, malic acid, succinic acid and carbonic acid, alkali or alkaline earth salt of one of these acids, Tris, histidine, meglumine, amino acids, sodium hydroxide, potassium hydroxide, hydrochloric acid and citric acid. 
     
     
         16 . A stable, liquid parenteral pharmaceutical formulation of fosaprepitant comprising:
 (i) fosaprepitant dimeglumine;   (ii) one or more stabilizing agents selected from polysorbates and β-cyclodextrins; and   (iii) a pH ranging from 7 to 13.   
     
     
         17 . The stable, liquid parenteral pharmaceutical formulation of  claim 16  wherein the fosaprepitant dimeglumine is present from approximately 0.1% to 15% w/w based on the total weight of the formulation. 
     
     
         18 . The stable, liquid parenteral pharmaceutical formulation of  claim 16  further comprising one or more chelating agents at a concentration from approximately 0.01% to approximately 5% w/w based on the total weight of the formulation. 
     
     
         19 . The stable, liquid parenteral pharmaceutical formulation of  claim 18 , wherein the one or more chelating agents are selected from EDTA, DTPA, DOTA and salts thereof. 
     
     
         20 . The stable, liquid parenteral pharmaceutical formulation of  claim 16  further comprising one or more pH adjusting agents and/or buffering agents. 
     
     
         21 . The stable, liquid parenteral pharmaceutical formulation of  claim 20  wherein the one or more pH adjusting agents and/or buffering agents are selected from phosphate buffer, citrate buffer, sodium carbonate, sodium bicarbonate, tartrate, benzoate, lactate, acetate, borate, glutaric acid, malic acid, succinic acid and carbonic acid, alkali or alkaline earth salt of one of these acids, Tris, histidine, meglumine, amino acids, sodium hydroxide, potassium hydroxide, hydrochloric acid and citric acid. 
     
     
         22 . The stable, liquid parenteral pharmaceutical formulation of  claim 16  further comprising one or more solvents. 
     
     
         23 . The stable, liquid parenteral pharmaceutical formulation of  claim 16  further comprising one or more amino acids selected from the group consisting of arginine, glycine, histidine and lysine. 
     
     
         24 . The stable, liquid parenteral pharmaceutical formulation of  claim 16  further comprising one or more tonicity modifiers. 
     
     
         25 . The stable, liquid parenteral pharmaceutical formulation of  claim 16  further comprising additional stabilizing surfactants selected from polyethylene glycol esters, sorbitan esters (e.g. Tweens), polyoxyethylated vegetable oil, polyethoxylated castor oil and sucrose fatty acid esters. 
     
     
         26 . The stable, liquid parenteral pharmaceutical formulation of  claim 16  further comprising additional stabilizing cyclodextrins selected from α and γ-cyclodextrin and cyclodextrins modified with alkyl-, hydroxyalkyl-, dialkyl-, and sulfoalkyl-ether modified cyclodextrins such as methyl or hydroxypropyl β-cyclodextrins (HPβCD), sulfoalkylether-substituted beta-cyclodextrin and sulfobutylether-β-cyclodextrin (SBECD).