We claim:
1. A crystalline form of Mitapivat hemisulfate of formula (1)
wherein crystalline form is characterized by powder X-Ray diffractogram
having at least one characteristic peaks at about 2 theta values 12.8, 20.3 and
23.2±0.2° degrees as depicted in figure 1.
2. The crystalline form of Mitapivat hemisulfate (1) as claimed in claim 1,
wherein the crystalline form is having characteristic XRPD peaks at 2 theta
values 10.4, 12.8, 15.8, 20.3, and 23.2 ±0.2° degrees.
3. The crystalline form of Mitapivat hemisulfate (1) as claimed in claim 1,
wherein the crystalline form is having characteristic XRPD peaks at 2 theta
values 5.29, 10.41, 11.39, 12.83, 13.80, 14.14, 14.60, 15.86, 16.63, 17.40,
17.93, 18.82, 19.57, 20.38, 20.88, 21.19, 21.74, 22.25, 22.79, 23.29, 24.04,
24.62, 25.87, 26.47, 27.05, 27.85, 28.43, 29.00, 29.77, 31.43, 32.44, 33.63,
15 35.75, 36.76, 39.18, and 47.08° degrees.
4. A process for preparing crystalline form of Mitapivat hemisulfate (1)
comprising the steps of:
a) dissolving Mitapivat free base (2) in a solvent or mixture of solvents,
b) heating the reaction mixture at a suitable temperature,
c) adding sulfuric acid to the reaction mixture obtained in step b),
d) adding one or more anti-solvent to the reaction mixture obtained in step
c), and
e) isolating crystalline form of Mitapivat hemi sulfate (1).
wherein crystalline form is characterized by powder X-Ray diffractogram
having at least one characteristic peaks at about 2 theta values 12.8, 20.3 and
23.2±0.2° degrees as depicted in figure 1.
5. A process for preparing crystalline form of Mitapivat hemisulfate (1)
comprising the steps of:
a) dissolving Mitapivat hemisulfate (1) in a solvent or mixture of solvents.
b) adding one or more anti-solvent to the solution obtained in step a); and
c) isolating crystalline form of Mitapivat hemisulfate (1).
wherein crystalline form is characterized by powder X-Ray diffractogram
having at least one characteristic peaks at about 2 theta values 12.8, 20.3 and
23.2±0.2° degrees as depicted in figure 1.
6. The process as claimed in claim 4 and 5, wherein the solvent is selected from
the group consisting of alcoholic solvents such as methanol, ethanol, 1 -
propanol, 2-propanol, 1-butanol, and 2-butanol; "polar-aprotic solvents" such
as dimethylacetamide, dimethylformamide, dimethylsulfoxide, N Methylpyrrolidone (NMP) and the like or its mixture thereof.
7. The process as claimed in claim 4 and 5, wherein the anti-solvent solvent is
selected from group consisting of "hydrocarbon solvents" such as n-heptane,
n-hexane, xylene, and toluene.; "ether solvents" such as dimethyl ether,
diethyl ether, diisopropyl ether, methyl tert-butyl ether, 1,2-dimethoxyethane,
tetrahydrofuran, 1,4-dioxane and the like or its mixture thereof.
8. A crystalline form of Mitapivat hemisulfate (1) characterized by Differential
Scanning Calorimetry having peak at 229°C ± 3°C as shown in figure 2.
9. A crystalline form of Mitapivat hemisulfate (1) is having particle size D90
less than 100ppm and residual solvent content comprising of Methanol,
Ethanol, Acetone, Isopropyl alcohol, Dichloromethane, Methyl tertiary butyl
ether, Isopropyl acetate, Tetrahydrofuran, Toluene, N, N-Dimethylformamide, Xylene, Pyridine, and N, N-Diisopropylethylamine are less than
1000 ppm.
10. A pharmaceutical composition comprising crystalline form of Mitapivat hemi
sulfate (1) as claimed in claim 1 and at least one pharmaceutically acceptable
excipient.