Processes of making L-ornithine phenylacetate

1. A process of making L-ornithine phenylacetate, comprising:

intermixing L-ornithine hydrochloride and potassium hydroxide in a first solvent to form a first reaction mixture, wherein the first solvent comprises water;

adding a second solvent to said first reaction mixture, wherein the second solvent comprises ethanol;

isolating potassium chloride from said first reaction mixture;

intermixing phenylacetic acid with said first reaction mixture to form a second reaction mixture; and

isolating a composition comprising L-ornithine phenylacetate from said second reaction mixture.

2. The process of claim 1 , further comprising cooling said first reaction mixture before isolating potassium chloride.

3. The process of claim 2 , wherein said first reaction mixture is cooled to about 0 to 5° C.

4. The process of claim 1 , wherein said first solvent is water.

5. The process of claim 1 , wherein said second solvent is ethanol.

6. The process of claim 1 , wherein the first reaction mixture after addition of the second solvent comprises about 1:1 (v/v) to 1:8 (v/v) water to ethanol.

7. The process of claim 1 , wherein phenylacetic acid is dissolved in a third solvent before intermixing with said first reaction mixture.

8. The process of claim 7 , wherein said third solvent comprises ethanol.

9. The process of claim 1 , wherein the molar ratio of potassium hydroxide to L-ornithine hydrochloride is at least about 1.1:1.

10. The process of claim 1 , wherein the molar ratio of phenylacetic acid to L-ornithine hydrochloride is at least about 1.2:1.

11. The process of claim 1 , wherein the chloride content of the composition comprising L-ornithine phenylacetate is less than about 2.5% by weight.

12. The process of claim 1 , further comprising recrystallizing the composition comprising L-ornithine phenylacetate.

13. The process of claim 12 , wherein the composition is recrystallized from a solvent mixture of water and methanol.

14. The process of claim 13 , wherein the volume ratio of water and methanol used in the recrystallization is from about 1:1 to about 1:10.

15. The process of claim 12 , wherein the chloride content of the recrystallized composition is less than about 0.1% by weight.

16. The process of claim 1 , wherein said composition comprises less than about 5.0% L-ornithine cyclization or dimerization side products.

17. The process of claim 1 , wherein said composition is free of L-ornithine cyclization or dimerization side products.

18. The process of claim 6 , wherein the first reaction mixture after addition of the second solvent comprises about 1:4 (v/v) water to ethanol.