Liquid formulations of fosaprepitant
The present invention relates to liquid formulations of Fosaprepitant intended for parenteral administration. Further the invention also describes process for preparing such formulations.
1. 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, at a concentration from approximately 0.01% to approximately 5% w/w based on the total weight of the formulation;
(iii) one or more stabilizing agents selected from polysorbates and β-cyclodextrins;
(iv) one or more pH adjusting agents and/or buffering agents;
(v) one or more solvents;
(vi) a pH ranging from 7 to 13; and
(vii) optionally other pharmaceutically acceptable excipients.
2. The stable, liquid parenteral pharmaceutical formulation of claim 1 comprising
(i) the one or more chelating agents are selected from EDTA, DTPA, DOTA and salts thereof;
(ii) the one or more solvents are selected from propylene glycol, glycerine, polyethylene glycol and water.
3. The stable, liquid parenteral pharmaceutical formulation of claim 2 , wherein the one or more stabilizing agents is polysorbate 80.
4. The stable, liquid parenteral pharmaceutical formulation of claim 2 , wherein the β-cyclodextrins are selected from hydroxypropyl β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBECD).
5. The stable, liquid parenteral pharmaceutical formulation of claim 2 , wherein the pH adjusting agents and/or buffering agents are selected from one or more of: phosphate buffer, citrate buffer, sodium carbonate, sodium bicarbonate, tartarate, 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.
6. The stable liquid parenteral formulation of claim 1 wherein the chelating agent is EDTA.
7. The stable liquid parenteral formulation of claim 1 wherein the one or more pharmaceutically acceptable excipients is an amino acid selected from the group consisting of arginine, glycine, histidine and lysine.
8. The stable liquid parenteral formulation of claim 1 wherein the one or more pharmaceutically acceptable excipients is arginine.
9. The stable liquid parenteral formulation of claim 1 wherein the one or more pharmaceutically acceptable excipients is one or more tonicity modifiers.
10. The stable liquid parenteral formulation of claim 1 wherein the one or more tonicity modifiers is mannitol.
11. The stable liquid parenteral formulation of claim 1 wherein the one or more stabilizing agents are one or more β-cyclodextrins.
12. The stable liquid parenteral formulation of claim 1 , wherein the one or more stabilizing agents is sulfobutyl-ether-β-cyclodextrin sodium salt.
13. The stable liquid parenteral formulation of claim 1 , wherein the quantity of the one or more stabilizing agents is from approximately 0.05% w/w to approximately 30% based on total weight of the formulation.
14. The stable liquid parenteral formulation of claim 1 , wherein the one or more stabilizing agents is hydroxy propyl beta cyclodextrin.
15. The stable liquid parenteral formulation of claim 1 , wherein after storage at 2-8° C. for at least 1 month, the concentration of aprepitant is not more than 10%.
16. The stable liquid parenteral formulation of claim 1 , wherein after storage at 2-8° C. for at least 1 month, the concentration of aprepitant is not more than 2%.
17. The stable liquid parenteral formulation of claim 2 , wherein the EDTA is present from approximately 0.1% to approximately 1.6% w/w based on the total weight of the formulation.