Terlipressin compositions and uses thereof

1. A pharmaceutical composition comprising terlipressin or a pharmaceutically acceptable salt thereof, a monovalent organic buffer salt comprising an acetate buffer salt in an amount that provides a total buffer concentration in the composition of 5 mM or less, and water, wherein the pharmaceutical composition has a pH of from about 4.5 to about 6.

2. The pharmaceutical composition of claim 1 , further comprising sodium chloride (NaCl).

3. The pharmaceutical composition of claim 1 , further comprising mannitol.

4. The pharmaceutical composition claim 1 , wherein the composition has a pH of about 4.8+0.3.

5. The pharmaceutical composition of claim 1 , wherein the acetate buffer salt is selected from one or more of sodium acetate, ammonium acetate, and potassium acetate.

6. The pharmaceutical composition of claim 1 , wherein the buffer salt is present in an amount to provide a total buffer concentration from about 0.1 mM to about 5 mM.

7. The pharmaceutical composition of claim 2 , comprising sodium chloride at a concentration from about 1 mg/mL to about 10 mg/mL.

8. The pharmaceutical composition of claim 1 , comprising mannitol at a concentration from about 30 mg/mL to about 70 mg/mL.

9. The pharmaceutical composition of claim 1 , comprising terlipressin or pharmaceutically acceptable salt thereof in an amount to provide from about 0.1 mg/mL to about 5 mg/mL terlipressin free base.

10. The pharmaceutical composition of claim 1 , comprising terlipressin acetate in an amount to provide from about 0.1 mg/mL to about 5 mg/mL terlipressin free base.

11. The pharmaceutical composition claim 1 , comprising terlipressin acetate in an amount to provide from about 0.1 mg/mL to about 5 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration ranging from about 0.1 mM to about 5 mM, optionally, sodium chloride at a concentration ranging from about 1 mg/mL to about 10 mg/mL, and water.

12. The pharmaceutical composition of claim 1 , consisting essentially of terlipressin acetate in an amount to provide from about 0.1 mg/mL to about 5 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration ranging from about 0.1 mM to about 5 mM, optionally, sodium chloride at a concentration ranging from about 1 mg/mL to about 10 mg/mL, and water.

13. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is selected from:

(a) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 0.1 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, sodium chloride at a concentration of about 9 mg/mL, and water, wherein the composition has a pH of about 4.8±0.3;

(b) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 1 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, sodium chloride at a concentration of about 9 mg/mL, and water, wherein the composition has a pH of about 4.8±0.3;

(c) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 2 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, sodium chloride at a concentration of about 9 mg/mL, and water, wherein the composition has a pH of about 4.8±0.3;

(d) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 3 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, sodium chloride at a concentration of about 9 mg/mL, and water, wherein the composition has a pH of about 4.8±0.3;

(e) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 4 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, sodium chloride at a concentration of about 9 mg/mL, and water, wherein the composition has a pH of about 4.8±0.3; and

(f) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 5 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, sodium chloride at a concentration of about 9 mg/mL, and water, wherein the composition has a pH of about 4.8±0.3.

14. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is selected from:

(a) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 0.1 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, and water, wherein the composition has a pH of about 4.8±0.3;

(b) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 1 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, and water, wherein the composition has a pH of about 4.8±0.3;

(c) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 2 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, and water, wherein the composition has a pH of about 4.8±0.3;

(d) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 3 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, and water, wherein the composition has a pH of about 4.8±0.3;

(e) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 4 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, and water, wherein the composition has a pH of about 4.8±0.3; and

(f) a pharmaceutical composition comprising terlipressin acetate in an amount to provide 5 mg/mL terlipressin free base, sodium acetate in an amount to provide a total acetate concentration of about 1 mM, and water, wherein the composition has a pH of about 4.8±0.3.

15. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is stable at room temperature for at least 1 year.

16. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition exhibits a stability such that one or more of:

(a) after being stored at 25° C. and 60% relative humidity for a period of time of at least one year, the total impurity content in the composition is less than about 1.9% w/w based on the total weight of the terlipressin;

(b) after being stored at 25° C. and 60% relative humidity for a period of time of 12 months, the total impurity content in the composition is less than about 1.9% w/w based on the total weight of the terlipressin;

(c) after being stored at 25° C. and 60% relative humidity for a period of time of 18 months, the total impurity content in the composition is less than about 1.9% w/w based on the total weight of the terlipressin;

(d) after being stored at 25° C. and 60% relative humidity for a period of time of 24 months, the total impurity content in the composition is less than about 1.9% w/w based on the total weight of the terlipressin; and

(e) after being stored at 25° C. and 60% relative humidity for a period of time of 36 months, the total impurity content in the composition is less than about 1.9% w/w based on the total weight of the terlipressin.