RUC-4 formulations

1 . A composition comprising Compound (1):

and acetic acid; wherein the composition is a solution in water having a pH of about 4.0-6.0, inclusive.

2 . The composition of claim 1 , wherein the molar ratio of Compound (1) to acetic acid is about 1:0.5 to about 1:3.5.

3 . The composition of claim 1 , further comprising an additional acid or acids.

4 . The composition of claim 3 , wherein the additional acid is hydrochloric acid.

5 . The composition of claim 1 , wherein the composition has an osmolality of ≥200 mmol/L.

6 . The composition of claim 1 , comprising about 1-100 mg/mL of Compound (1).

7 . The composition of claim 1 , comprising about 3-15 mg/mL of acetic acid.

8 . The composition of claim 1 , further comprising a polyol.

9 . The composition of claim 1 , further comprising about 1-10 mg/mL citric acid.

10 . The composition of claim 1 , further comprising Compound (2):

or a salt thereof.

11 . The composition of claim 1 , further comprising Compound (3):

or a salt thereof.

12 . The composition of claim 1 , comprising the following components per milliliter of water:

Compound (1)

18

mg

Acetic acid

5.59

mg

Hydrochloric acid

qs to pH 5.0 ± 0.1

Glycerin

14

mg

wherein the composition has a pH of 5.0±0.1;

Compound (1)

17.5 mg

Acetic acid

5.43 mg

Hydrochloric acid

1.53 mg

Glycerin

14.6 mg

wherein the composition has a pH of 4.75±0.1;

Compound (1)

15

mg

Acetic acid

4.66

mg

Hydrochloric acid

1.31

mg

Glycerin

16.3

mg

wherein the composition has a pH of 4.75±0.1;

Compound (1)

15

mg

Acetic acid

4.66

mg

Hydrochloric acid

0.88

mg

Glycerin

18.5

mg

wherein the composition has a pH of 5.0±0.1;

Compound (1)

18

mg

Acetic acid

5.6

mg

Anhydrous Citric Acid

1.35

mg

Hydrochloric acid

0.93 mg (QS pH to 4.75)

Glycerin

16

mg

wherein the composition has a pH of 4.75±0.1;

Compound (1)

18

mg

Acetic acid

5.6

mg

Anhydrous Citric Acid

1.35

mg

Hydrochloric acid

1.4 mg (QS pH to 4.5)

Glycerin

16.3

mg

wherein the composition has a pH of 4.5±0.1; or

Compound (1)

18

mg

Acetic acid

5.6

mg

Anhydrous Citric Acid

1.35

mg

Hydrochloric acid

1.97 mg (QS pH to 4.25)

Glycerin

18.5

mg

wherein the composition has a pH of 4.25±0.1.

13 . The composition of claim 1 , wherein the composition is stable for at least 1 month at 25° C./60% RH, at least 3 months at 25° C./60% RH, at least 6 months at 25° C./60% RH, or at least 12-18 months at 25° C./60% RH.

14 . A composition comprising Compound (1):

in the form of a salt of acetic acid, wherein the molar ratio of Compound (1) to acetic acid is in the range of about 1:0.2 to about 1:3.5.

15 . The composition of claim 14 , wherein the molar ratio of Compound (1) to acetic acid is in the range of about 1:0.5 to about 1:3.5.

16 . The composition of claim 14 , wherein the composition is a solid lyophile.

17 . The composition of claim 16 , comprising less than 5% by weight of Compound (4):

or a salt thereof.

18 . A method of making a lyophilized composition of claim 16 , comprising:

providing a solution comprising Compound (1) and acetic acid;

filtering the solution;

freezing the solution; and

removing the water from the frozen solution by sublimation at low pressure.

19 . A method of making a solution of Compound (1) for administration by injection, comprising contacting Compound (1), or a pharmaceutically acceptable salt thereof, or a lyophile according to claim 16 with a pharmaceutically acceptable solvent in a syringe.

20 . The composition of claim 1 , wherein the molar ratio of Compound (1) to acetic acid is about 1:0.5.

21 . The composition of claim 1 , wherein the composition comprises about 1 mg/mL to about 5 mg/mL acetic acid.

22 . The composition of claim 8 , wherein the composition comprises about 12-18 mg/mL polyol.

23 . The composition of claim 1 , comprising the following components per milliliter of water:

Compound (1)

18 mg

Acetic acid

5.59 mg  

Hydrochloric acid

qs to pH 5.0 ± 0.1

Glycerin

14 mg

wherein the composition has a pH of 5.0±0.1.