Vasopressin liquid formulations

1. A liquid pharmaceutical composition for intravenous administration comprising:

i) vasopressin or a pharmaceutically acceptable salt thereof;

ii) a buffer comprising lactic acid, a lactate salt, or a combination thereof;

iii) water; and

iv) optionally, a pH adjuster;

wherein the pharmaceutical composition has a pH of from about 3.0 to about 4.1; and wherein, as measured by HPLC, the pharmaceutical composition retains 90% or more of the initial concentration of vasopressin or pharmaceutically acceptable salt thereof after storage for at least 18 months when stored at about 25° C. and about 60% relative humidity.

2. The pharmaceutical composition of claim 1 having a pH of from about 3.2 to about 3.4.

3. The pharmaceutical composition of claim 2 having a pH of about 3.3.

4. The pharmaceutical composition of claim 1 , wherein the lactate buffer has a concentration of from about 1 to about 20 mM.

5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is free of a non-lactate buffer.

6. The pharmaceutical composition of claim 5 , wherein the non-lactate buffer is an acetate buffer.

7. The pharmaceutical composition of claim 1 , wherein the vasopressin is a vasopressin salt selected from the group consisting of acetate or trifluoroacetate.

8. The pharmaceutical composition of claim 1 further comprising one or more pharmaceutically acceptable excipients.

9. The pharmaceutical composition of claim 8 , wherein the one or more pharmaceutically acceptable excipients comprises a preservative.

10. The pharmaceutical composition of claim 1 , wherein the composition is free of a preservative.

11. The pharmaceutical composition of claim 1 , wherein as measured by HPLC, the pharmaceutical composition retains 90% or more of the initial concentration of vasopressin or pharmaceutically acceptable salt thereof after storage for at least 20 months.

12. The pharmaceutical composition of claim 11 having a pH of from about 3.2 to about 3.4.

13. The pharmaceutical composition of claim 12 having a pH of about 3.3.

14. The pharmaceutical composition of claim 1 , wherein, as measured by HPLC, the pharmaceutical composition retains 90% or more of the initial concentration of vasopressin or pharmaceutically acceptable salt thereof after storage for at least 72 months at about 5° C.

15. The pharmaceutical composition of claim 14 having a pH of from about 3.2 to about 3.4.

16. The pharmaceutical composition of claim 15 having a pH of about 3.3.

17. The pharmaceutical composition of claim 1 , comprising a concentration of vasopressin or pharmaceutically acceptable salt thereof of between about 0.01 mg/mL and about 0.3 mg/mL.

18. The pharmaceutical composition of claim 17 , comprising a concentration of vasopressin or pharmaceutically acceptable salt thereof of between about 0.02 mg/mL and about 0.07 mg/mL.

19. The pharmaceutical composition of claim 17 , comprising a concentration of vasopressin or pharmaceutically acceptable salt thereof of between about 0.15 mg/mL and about 0.20 mg/m L.

20. The pharmaceutical composition of claim 1 , wherein the composition retains about 95% or more of the initial concentration of vasopressin or pharmaceutically acceptable salt thereof.

21. The pharmaceutical composition of claim 1 , wherein, as measured by HPLC, the pharmaceutical composition contains not more than about 2% of an individual degradant after storage at about 5° C. for about 6 months.

22. The pharmaceutical composition of claim 21 , wherein, as measured by HPLC, the pharmaceutical composition contains not more than about 1% of an individual degradant after storage at about 5° C. for about 6 months.

23. The pharmaceutical composition of claim 1 , wherein, as measured by HPLC, the pharmaceutical composition contains not more than about 3% of an individual degradant after storage at about 25° C. and about 60% relative humidity for about 6 months.

24. The pharmaceutical composition of claim 23 , wherein, as measured by HPLC, the pharmaceutical composition contains not more than about 2% of an individual degradant after storage at about 25° C. and about 60% relative humidity for about 6 months.

25. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is stored in a glass vial.

26. A pharmaceutical composition for intravenous administration consisting of:

i) between 0.02 mg/mL and 0.05 mg/mL vasopressin or a pharmaceutically acceptable salt thereof;

ii) a buffer consisting of lactic acid, a lactate salt, or a combination thereof;

iii) water; and

iv) optionally, a pH adjuster,

wherein the pharmaceutical composition has a pH of from about 3.0 to about 3.7; and wherein, as measured by HPLC, the pharmaceutical composition retains 90% or more of the initial concentration of vasopressin or pharmaceutically acceptable salt thereof after storage for at least 18 months when stored at about 25° C. and about 60% relative humidity.

27. The pharmaceutical composition of claim 26 , wherein the pH is from about 3.2 to about 3.4.

28. The pharmaceutical composition of claim 27 , wherein the pharmaceutical composition retains 90% or more of the initial concentration of vasopressin or pharmaceutically acceptable salt thereof after storage for at least 20 months.

29. A pharmaceutical composition for intravenous administration consisting of:

i) between 0.15 mg/mL and 0.25 mg/mL vasopressin or a pharmaceutically acceptable salt thereof;

ii) a buffer consisting of lactic acid, a lactate salt, or a combination thereof;

iii) water; and

iv) optionally, a pH adjuster,

wherein the pharmaceutical composition has a pH of from about 3.0 to about 3.5; and wherein, as measured by HPLC, the pharmaceutical composition retains about 90% or more of the initial concentration of vasopressin or pharmaceutically acceptable salt thereof after storage for about 18 months when stored at about 25° C. and about 60% relative humidity.

30. The pharmaceutical composition of claim 29 , wherein the pH is from about 3.2 to about 3.4.

31. The pharmaceutical composition of claim 30 , wherein the pharmaceutical composition retains 90% or more of the initial concentration of vasopressin or pharmaceutically acceptable salt thereof after storage for at least 20 months.

32. A method of increasing blood pressure in a patient in need thereof, the method comprising:

a) providing a pharmaceutical composition comprising:

i) vasopressin or a pharmaceutically acceptable salt thereof;

ii) a buffer comprising lactic acid, a lactate salt, or a combination thereof;

iii) water, and

iv) optionally, a pH adjuster,

wherein the pharmaceutical composition has a pH of from 3.0 to 4.1; and

wherein, as measured by HPLC, the pharmaceutical composition retains 90% or more of the initial concentration of vasopressin or pharmaceutically acceptable salt thereof after storage at about 25° C. and 60% relative humidity for about 18 months; and

b) intravenously administering the pharmaceutical composition to the patient.

33. The method of claim 32 , wherein the pharmaceutical composition has a pH of from 3.2 to 3.4.

34. The method of claim 33 , wherein the pharmaceutical composition has a pH of about 3.3.

35. The method of claim 32 , wherein, as measured by HPLC, the pharmaceutical composition retains 90% or more of the initial vasopressin concentration after storage at about 25° C. and 60% relative humidity for about 20 months.

36. The method of claim 35 , wherein the pharmaceutical composition retains 90% or more of the initial vasopressin concentration after storage at about 5° C. for about 18 months.

37. The method of claim 32 , wherein the pharmaceutical composition is free of a non-lactate buffer.

38. The method of claim 37 , wherein the non-lactate buffer is acetate buffer.

39. The pharmaceutical composition of claim 1 , wherein the composition is a concentrate requiring dilution prior to administration.