Stabilized liquid formulation of levothyroxine
The present invention relates to stabilized liquid formulations of Levothyroxine or a pharmaceutically acceptable salt thereof, intended for parenteral administration. Further this invention also describes process of preparing such compositions.
1. A stable, liquid parenteral pharmaceutical formulation of levothyroxine comprising:
(i) levothyroxine sodium in a concentration of less than 0.1% w/v;
(ii) a solubilizing agent comprising a cyclodextrin;
(iii) optionally one or more stabilizing agents;
(iv) arginine in a concentration of less than 0.20 M; and
(v) one or more solvents, wherein the pH is between 5 and 7.
2. The liquid parenteral pharmaceutical formulation of claim 1 , wherein the stabilizing agents are selected from one or both sodium iodide and potassium iodide.
3. The liquid parenteral pharmaceutical formulation of claim 1 wherein the cyclodextrin is sulfobutylether-β-cyclodextrin (SBECD).
4. The liquid parenteral pharmaceutical formulation of claim 1 , wherein the solvent is water.
5. The liquid parenteral pharmaceutical formulation of claim 1 , wherein the solvent is propylene glycol.
6. The liquid parenteral pharmaceutical formulation of claim 1 , wherein the pH of the formulation is 6.
7. The liquid parenteral pharmaceutical formulation of claim 1 , wherein the cyclodextrin is selected from α, β and γ-cyclodextrin and cyclodextrins modified with alkyl-, hydroxyalkyl-, dialkyl-, and sulfoalkyl-ether modified cyclodextrins.
8. A stable, liquid parenteral pharmaceutical formulation of levothyroxine comprising:
(i) levothyroxine sodium;
(ii) sulfobutylether-β-cyclodextrin (SBECD)
(iii) arginine in a concentration of less than 0.20 M; and
(iv) one or more solvents, wherein the pH is between 5 and 7.
9. The liquid parenteral pharmaceutical formulation of claim 8 , wherein the pH of the formulation is 6.
10. The liquid parenteral pharmaceutical formulation of claim 8 , wherein arginine is in a concentration between approximately 0.06M to approximately 0.0001M.