RXR agonist salt form, polymorphs thereof, and uses thereof
Provided herein are salt and solid forms of (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid, including a Tris salt form of (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid, and polymorphs thereof, methods of preparing the compounds, and their uses.
1. A salt of (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid, which is an anhydrate, hemihydrate, monohydrate, or dihydrate of (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid tris(hydroxymethyl)aminomethane.
2. A solid form, which is Form A of the salt (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid mono-(tris(hydroxymethyl)aminomethane).
3. The solid form of claim 2 , having an X-ray powder diffraction pattern comprising a signal, in terms of 2θ, at 11.3±0.2°.
4. The solid form of claim 2 , having an X-ray powder diffraction pattern comprising signals, in terms of 2θ, at 3.8±0.2°, 7.6±0.2°, 11.3±0.2°, 18.1±0.2°, and 19.6±0.2°.
5. The solid form of claim 2 , having an X-ray powder diffraction pattern substantially as shown in FIG. 1 .
6. The solid form of claim 2 , having a differential scanning calorimetry thermogram comprising an endothermic transition at 154±3° C.
7. The solid form of claim 2 , having a differential scanning calorimetry thermogram substantially as shown in FIG. 2 .
8. The solid form of claim 2 , having a thermogravimetric analysis substantially as shown in FIG. 3 .
9. A solid form, which is Form B of the salt (2E,4E)-3-methyl-5-((1 S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-v1)cyclopropyl)penta-2,4-dienoic acid mono-(tris(hydroxymethyl)aminomethane).
10. The solid form of claim 9 , having an X-ray powder diffraction pattern comprising a signal, in terms of 2θ, at 11.5±0.2°.
11. The solid form of claim 9 , having an X-ray powder diffraction pattern comprising signals, in terms of 2θ, at 3.9±0.2°, 11.5±0.2°, 18.3±0.2°, 19.9±0.2°, and 23.2±0.2°.
12. The solid form of claim 9 , having an X-ray powder diffraction pattern substantially as shown in FIG. 4 .
13. The solid form of claim 9 , having a differential scanning calorimetry thermogram comprising an endothermic transition at 150±3° C.
14. The solid form of claim 9 , having a differential scanning calorimetry thermogram substantially as shown in FIG. 5 .
15. The solid form of claim 9 , having a thermogravimetric analysis substantially as shown in FIG. 6 .
16. The solid form of claim 2 , which is substantially purified.
17. The solid form of claim 2 , which is crystalline.
18. The solid form of claim 2 , prepared by a process comprising precipitating the solid form from a solution comprising (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid tris(hydroxymethyl)aminomethane and a solvent.
19. The solid form of claim 18 , wherein the solvent comprises ethanol, isopropanol, butanol, or a combination thereof, and the solvent further comprises 0 to about 1 volume % of water.
20. A process for preparing the solid form of claim 2 , comprising precipitating the solid form from a solution comprising (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid tris(hydroxymethyl)aminomethane and a solvent,
wherein the solvent comprises ethanol, isopropanol, butanol, or a combination thereof, and the solvent further comprises 0 to about 1 volume % of water.