Formulations of AG10
The present disclosure provides high-load tablet formulations of AG10 or a pharmaceutically acceptable salt thereof. In some aspects, provided herein are table formulations of AG10 or a pharmaceutically acceptable salt thereof that include at least 40% or more AG10 by weight and at least one pharmaceutical excipient selected from one or more fillers, one or more binders, one or more disintegrants, and one or more lubricants.
1. A tablet formulation comprising AG10 or a pharmaceutically acceptable salt thereof and one or more fillers, one or more disintegrants, and one or more lubricants, wherein
said tablet formulation comprises:
40 to 85% by weight of AG10 or a pharmaceutically acceptable salt thereof;
5 to 55% by weight of said one or more fillers;
3 to 8% by weight of said one or more disintegrants; and
0.5 to 3% by weight of said one or more lubricants, and wherein said one or more fillers comprise a high-grade microcrystalline cellulose characterized by cellulose polymers with (i) spherical morphology and porous structure or (ii) needle-like particle shape.
2. The tablet formulation of claim 1 , comprising about 50 to 75% by weight of AG10 or a pharmaceutically acceptable salt thereof.
3. The tablet formulation of claim 1 , comprising about 50% by weight of AG10 or a pharmaceutically acceptable salt thereof.
4. The tablet formulation of claim 1 , comprising about 66.7% by weight of AG10 or a pharmaceutically acceptable salt thereof.
5. The tablet formulation of claim 1 , comprising about 75% by weight of AG10 or a pharmaceutically acceptable salt thereof.
6. The tablet formulation of claim 1 , wherein said one or more fillers comprises about 10 to 50% by weight of said tablet formulation.
7. The tablet formulation of claim 1 , wherein said one or more fillers comprises about 15 to 45% by weight of said tablet formulation.
8. The tablet formulation of claim 1 , wherein said one or more fillers further comprise silicon dioxide.
9. The tablet formulation of claim 1 , wherein said one or more disintegrants comprises about 6% by weight of said tablet formulation.
10. The tablet formulation of claim 1 , wherein said one or more disintegrants is croscarmellose sodium.
11. The tablet formulation of claim 1 , wherein said one or more lubricants comprises about 1.5% by weight of said tablet formulation.
12. The tablet formulation of claim 11 , wherein said one or more lubricants comprise magnesium stearate.
13. The tablet formulation of claim 1 , wherein said tablet formulation is at least 75% dissolved after performance of a dissolution test in a solution of 0.1N HCl at 37±0.5° C. in an Apparatus-II (Paddles) with a paddle speed of about 50 rpm for 10 minutes.
14. The tablet formulation of claim 13 , wherein said tablet formulation is at least 85% dissolved after performance of said dissolution.
15. The tablet formulation of claim 14 , wherein said tablet formulation is at least 95% dissolved after performance of said dissolution.
16. The tablet formulation of claim 13 , wherein said dissolution test is performed at least three months after preparation of said tablet formulation.
17. The tablet formulation of claim 1 , further comprising a coating agent.
18. The tablet formulation of claim 1 , wherein AG10 is the pharmaceutically acceptable salt form of Formula Ia
19. A method of treating transthyretin amyloid (ATTR) cardiomyopathy comprising administering a tablet formulation of claim 1 .
20. A method of treating transthyretin amyloid (ATTR) polyneuropathy comprising administering a tablet formulation of claim 1 .
21. The tablet formulation of claim 1 , wherein said one or more fillers comprises about 25.8% by weight of said tablet formulation.
22. The tablet formulation of claim 1 , wherein said one or more fillers comprises about 42.5% by weight of said tablet formulation.
23. A tablet formulation comprising AG10 or a pharmaceutically acceptable salt thereof and one or more fillers, one or more disintegrants, and one or more lubricants, wherein
said tablet formulation comprises:
50 to 75% by weight of AG10 or a pharmaceutically acceptable salt thereof;
15 to 45% by weight of said one or more fillers;
3 to 8% by weight of said one or more disintegrants; and
0.5 to 3% by weight of said one or more lubricants, and
wherein said one or more fillers comprise a high-grade microcrystalline cellulose characterized by cellulose polymers with (i) spherical morphology and porous structure or (ii) needle-like particle shape.
24. The tablet formulation of claim 23 , wherein AG10 is the pharmaceutically acceptable salt form of Formula Ia
25. A method of treating transthyretin amyloid (ATTR) cardiomyopathy comprising administering a tablet formulation of claim 23 .
26. A method of treating transthyretin amyloid (ATTR) polyneuropathy comprising administering a tablet formulation of claim 23 .