Compositions comprising an RNA polymerase inhibitor and cyclodextrin for treating viral infections
The present disclosure provides a composition comprising Compound 1, or a pharmaceutically acceptable salt thereof, cyclodextrin, and, optionally, pH adjusting agents.
1. A composition comprising Compound 1
or a pharmaceutically acceptable salt thereof, and
cyclodextrin;
wherein the composition is a lyophilized composition,
wherein the composition comprises less than about 1% of impurity via HPLC following
storage for 18 months at a temperature of 25° C. (±1° C.) and a relative humidity of 60% (±1%).
2. The composition of claim 1 , wherein the cyclodextrin is a beta-cyclodextrin.
3. The composition of claim 2 , wherein the beta-cyclodextrin is sulfobutylalkyl ether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.
4. The composition of claim 2 , wherein the beta-cyclodextrin is betadex-sulfobutylether sodium.
5. The composition of claim 1 , comprising less than about 0.5% of impurity via HPLC.
6. The composition of claim 1 , further comprising a pH adjusting agent.
7. The composition of claim 6 , wherein the pH adjusting agent comprises HCl, NaOH, or a combination thereof.
8. The composition of claim 6 , wherein the pH adjusting agent is HCl.
9. The composition of claim 6 , wherein the pH adjusting agent is NaOH.
10. The composition of claim 1 , wherein the composition has a pH of about 3 to about 4.
11. The composition of claim 6 , comprising
Compound 1 in an amount from 1% to 10% w/w; and
cyclodextrin in an amount from 90% to 99% w/w.
12. The composition of claim 6 , comprising
Compound 1 in an amount from 1% to 5% w/w; and
cyclodextrin in an amount from 95% to 99% w/w.
13. The composition of claim 6 , comprising
Compound 1 in an amount from 2% to 4% w/w; and
cyclodextrin in an amount from 96% to 98% w/w.
14. The composition of claim 6 , comprising
Compound 1 in an amount from 3% to 3.5% w/w; and
cyclodextrin in an amount from 96.5% to 97% w/w.
15. The composition of claim 6 , comprising
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.
16. The composition of claim 6 , consisting essentially of
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.
17. A composition comprising Compound 1
or a pharmaceutically acceptable salt thereof, and
cyclodextrin;
wherein the composition is a lyophilized composition;
wherein the composition comprises less than about 1% of impurity via HPLC following
storage for 18 months at a temperature of 30° C. (±1° C.) and a relative humidity of 75% (±1%).
18. The composition of claim 17 , wherein the cyclodextrin is a beta-cyclodextrin.
19. The composition of claim 18 , wherein the beta-cyclodextrin is sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.
20. The composition of claim 18 , wherein the beta-cyclodextrin is betadex-sulfobutylether sodium.
21. The composition of claim 17 , comprising less than about 0.5% of impurity via HPLC.
22. The composition of claim 17 , further comprising a pH adjusting agent.
23. The composition of claim 22 , wherein the pH adjusting agent comprises HCl, NaOH, or a combination thereof.
24. The composition of claim 22 , wherein the pH adjusting agent is HCl.
25. The composition of claim 22 , wherein the pH adjusting agent is NaOH.
26. The composition of claim 17 , wherein the composition has a pH of about 3 to about 4.
27. The composition of claim 22 , comprising
Compound 1 in an amount from 1% to 10% w/w; and
cyclodextrin in an amount from 90% to 99% w/w.
28. The composition of claim 22 , comprising
Compound 1 in an amount from 1% to 5% w/w; and
cyclodextrin in an amount from 95% to 99% w/w.
29. The composition of claim 22 , comprising
Compound 1 in an amount from 2% to 4% w/w; and
cyclodextrin in an amount from 96% to 98% w/w.
30. The composition of claim 22 , comprising
Compound 1 in an amount from 3% to 3.5% w/w; and
cyclodextrin in an amount from 96.5% to 97% w/w.
31. The composition of claim 22 , comprising
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.
32. The composition of claim 22 , consisting essentially of
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.
33. A composition comprising Compound 1
or a pharmaceutically acceptable salt thereof, and
cyclodextrin;
wherein the composition is a lyophilized composition;
wherein the composition comprises less than about 1% of impurity via HPLC following
storage for 6 months at a temperature of 40° C. (±1° C.) and a relative humidity of 75% (±1%).
34. The composition of claim 33 , wherein the cyclodextrin is a beta-cyclodextrin.
35. The composition of claim 34 , wherein the beta-cyclodextrin is sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.
36. The composition of claim 34 , wherein the beta-cyclodextrin is betadex-sulfobutylether sodium.
37. The composition of claim 33 , comprising less than about 0.5% of impurity via HPLC.
38. The composition of claim 33 , further comprising a pH adjusting agent.
39. The composition of claim 38 , wherein the pH adjusting agent comprises HCl, NaOH, or a combination thereof.
40. The composition of claim 38 , wherein the pH adjusting agent is HCl.
41. The composition of claim 38 , wherein the pH adjusting agent is NaOH.
42. The composition of claim 33 , wherein the composition has a pH of about 3 to about 4.
43. The composition of claim 38 , comprising
Compound 1 in an amount from 1% to 10% w/w; and
cyclodextrin in an amount from 90% to 99% w/w.
44. The composition of claim 38 , comprising
Compound 1 in an amount from 1% to 5% w/w; and
cyclodextrin in an amount from 95% to 99% w/w.
45. The composition of claim 38 , comprising
Compound 1 in an amount from 2% to 4% w/w; and
cyclodextrin in an amount from 96% to 98% w/w.
46. The composition of claim 38 , comprising
Compound 1 in an amount from 3% to 3.5% w/w; and
cyclodextrin in an amount from 96.5% to 97% w/w.
47. The composition of claim 38 , comprising
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.
48. The composition of claim 38 , consisting essentially of
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.