NOVEL FORM OF BARDOXOLONE METHYL
The present disclosure relates to a formic acid solvate of bardoxolone methyl and to a process for its preparation. The present disclosure also relates to pharmaceutical compositions comprising the formic acid solvate of bardoxolone methyl and to its use in a method for treating a disease.
1 . Formic acid solvate of bardoxolone methyl.
2 . The formic acid solvate of bardoxolone methyl of claim 1 , which is a di-formic acid solvate, wherein the di-formic acid solvate is Form A.
3 . The formic acid solvate of bardoxolone methyl of claim 2 , which is characterized by having at least 2 or more X-ray powder diffraction peaks selected from about 8.2, 11.4, 12.3, 17.0, and 24.7° 2Θ±0.2° 2Θ as measured by CuKα radiation.
4 . The formic acid solvate of bardoxolone methyl of claim 3 , further comprising one or more X-ray powder diffraction peaks selected from about 8.9, 13.8, and 16.7° 2Θ±0.2° 2Θ as measured by CuKα radiation.
5 . The formic acid solvate of bardoxolone methyl of claim 2 , which is characterized by an onset of an endothermic event at about 101° C.±3° C., as measured by differential scanning calorimetry.
6 . A process for the preparation of the formic acid solvate of bardoxolone methyl of claim 1 comprising:
a) dissolving bardoxolone methyl in formic acid to form a solution; and
b) allowing the formic acid solvate of bardoxolone methyl to precipitate from the solution.
7 . The process of claim 6 , wherein the formic acid solvate of bardoxolone methyl is Form A.
8 . The process of claim 6 , wherein the weight to volume ratio of bardoxolone methyl to formic acid is about 70 mg/mL to about 200 mg/mL.
9 . The process of claim 6 , wherein the dissolving occurs at ambient temperature.
10 . The process of claim 6 , further comprising:
c) separating the formic acid solvate of bardoxolone methyl precipitate from the solution; and
d) subjecting the solution to fast evaporation, slow evaporation, or a combination of fast and slow evaporation resulting in the formic acid solvate of bardoxolone methyl.
11 . The process of claim 10 , wherein the formic acid solvate of bardoxolone methyl of step d) is Form A.
12 . A process for the preparation of the formic acid solvate of bardoxolone methyl of claim 1 comprising:
a) dissolving bardoxolone methyl in formic acid to form a solution; and
b) subjecting the solution to fast evaporation, slow evaporation, or a combination of fast and slow evaporation resulting in the formic acid solvate of bardoxolone methyl.
13 . The process of claim 12 , wherein the formic acid solvate of bardoxolone methyl is Form A.
14 . The process of claim 12 , wherein the weight to volume ratio of bardoxolone methyl to formic acid is about 70 mg/mL to about 200 mg/mL.
15 . The process of claim 12 , wherein the dissolving occurs at ambient temperature.
16 . The process of claim 12 , wherein the fast evaporation comprises vacuum drying the solution at about −30 mm Hg and about 50° C.
17 . The process of claim 12 , wherein the slow evaporation comprises exposing the solution to atmospheric pressure and ambient temperature.
18 . The formic acid solvate of bardoxolone methyl of claim 2 , which has single crystal parameters:
a=6.4 ű1.5%
b=11.2 ű1.5%
c=21.5 ű1.5%
α=γ=90°
β=97°±3°
19 . The formic acid solvate of bardoxolone methyl of claim 2 , which has a cell volume of about 1541 Å 3 ±3%.
20 . The formic acid solvate of bardoxolone methyl of claim 2 , which has a monoclinic space group.
21 . The formic acid solvate of bardoxolone methyl of claim 18 , which has a P2 1 space group.