Phospholipid formulations of 1′-cyano substituted carba-nucleoside analogs
The disclosure provides pharmaceutical formulations of the compound of Formula I: or a pharmaceutically acceptable salt thereof.
1. A pharmaceutical formulation comprising:
a. phospholipids;
b. a compound of Formula I:
or a pharmaceutically acceptable salt thereof; and
c. sucrose;
wherein the phospholipids comprise a phosphatidyl choline and an anionic phospholipid.
2. The pharmaceutical formulation of claim 1 , wherein the compound of Formula I is a compound of Formula Ia:
3. The pharmaceutical formulation of claim 1 , wherein at least about 60% of fatty acid chains of the phosphatidyl choline comprise 16 or more carbon atoms.
4. The pharmaceutical formulation of claim 1 , wherein at least about 60% of fatty acid chains of the phosphatidyl choline comprise 18 or more carbon atoms.
5. The pharmaceutical formulation of claim 1 , wherein at least about 50% of fatty acid chains of the phosphatidyl choline comprise at least one carbon-carbon double bond.
6. The pharmaceutical formulation of claim 1 , wherein the phosphatidyl choline is Soy-PC, egg-PC, DEPC, or DOPC.
7. The pharmaceutical formulation of claim 6 , wherein the phosphatidyl choline is soy-PC or egg PC.
8. The pharmaceutical formulation of claim 1 , wherein at least about 60% of fatty acid chains of the anionic phospholipid choline comprise 14 or more carbon atoms.
9. The pharmaceutical formulation of claim 1 , wherein at least about 60% of fatty acid chains of the anionic phospholipid choline comprise 16 or more carbon atoms.
10. The pharmaceutical formulation of claim 1 , wherein at least about 60% of fatty acid chains of the anionic phospholipid choline comprise 18 or more carbon atoms.
11. The pharmaceutical formulation of claim 1 , wherein the anionic phospholipid is selected form the group consisting of Egg-PG, Soy-PG, DSPG, DEPG, DOPG, DSPA, DPPA, DEPA, DOPA, DSPS, DPPS, DEPS, and DOPS, and mixtures thereof.
12. The pharmaceutical formulation of claim 11 , wherein the anionic phospholipid is DSPG.
13. The pharmaceutical formulation of claim 1 , wherein the phospholipids and the compound of Formula I are present in a weight ratio of about 5:1 to about 25:1.
14. The pharmaceutical formulation of claim 13 , wherein the phospholipids and the compound of Formula I are present in a weight ratio of about 15:1.
15. The pharmaceutical formulation of claim 1 , wherein the phosphatidyl choline and the anionic phospholipid are present in a molar ratio of about 1:1 to about 20:1.
16. The pharmaceutical formulation of claim 15 , wherein the phosphatidyl choline and the anionic phospholipid are present in a molar ratio of about 10:1.
17. The pharmaceutical formulation of claim 1 , further comprising a buffer.
18. The pharmaceutical formulation of claim 1 , wherein the sucrose is present in an amount of about 1% to about 25%.
19. The pharmaceutical formulation of claim 18 , wherein the sucrose is present in an amount of about 9%.
20. The pharmaceutical formulation of claim 18 , wherein the sucrose is present in an amount of about 18%.
21. The pharmaceutical formulation of claim 1 , wherein the compound of Formula I is present in an amount of about 0.1 mg/mL to about 20 mg/mL relative to total volume of the pharmaceutical formulation.
22. The pharmaceutical formulation of claim 21 , wherein the compound of Formula I is present in an amount of about 6 mg/mL to about 7 mg/mL relative to total volume of the pharmaceutical formulation.
23. The pharmaceutical formulation of claim 22 , wherein the compound of Formula I is present in an amount of about 6.67 mg/mL relative to total volume of the pharmaceutical formulation.
24. The pharmaceutical formulation of claim 21 , wherein the compound of Formula I is present in an amount of about 1 mg/mL to about 5 mg/mL relative to total volume of the pharmaceutical formulation.
25. The pharmaceutical formulation of claim 24 , wherein the compound of Formula I is present in an amount of about 3 mg/mL to about 4 mg/mL relative to total volume of the pharmaceutical formulation.
26. The pharmaceutical formulation of claim 25 , wherein the compound of Formula I is present in an amount of about 3.33 mg/mL relative to total volume of the pharmaceutical formulation.
27. The pharmaceutical formulation of claim 1 , wherein the pharmaceutical formulation has a pH of about 2.0 to about 7.0.
28. The pharmaceutical formulation of claim 1 , wherein the pharmaceutical formulation is a lyophilized formulation.
29. A method of treating or preventing a viral infection in a human in need thereof, the method comprising administering to the human the pharmaceutical formulation of claim 1 .
30. The pharmaceutical formulation of claim 13 , wherein the phosphatidyl choline and the anionic phospholipid are present in a molar ratio of about 1:1 to about 20:1.
31. The pharmaceutical formulation of claim 14 , wherein the phosphatidyl choline and the anionic phospholipid are present in a molar ratio of about 1:1 to about 20:1.
32. The pharmaceutical formulation of claim 13 , wherein the phosphatidyl choline and the anionic phospholipid are present in a molar ratio of about 10:1.
33. The pharmaceutical formulation of claim 14 , wherein the phosphatidyl choline and the anionic phospholipid are present in a molar ratio of about 10:1.