Form of ponatinib
The present disclosure relates to Form Z of acetic acid solvated hydrate of ponatinib hydrochloride. The present disclosure is also related to processes for the preparation of Form Z of acetic acid solvated hydrate of ponatinib hydrochloride. Further, the present disclosure also relates to pharmaceutical compositions comprising Form Z of acetic acid solvated hydrate of ponatinib hydrochloride and methods for treating disease using Form Z of acetic acid solvated hydrate of ponatinib hydrochloride.
1. A compound which is an acetic acid solvated hydrate of ponatinib hydrochloride.
2. The compound according to claim 1 , wherein the compound is a monohydrate.
3. The compound according to claim 1 , wherein the compound is characterized by having at least 2 or more X-ray powder diffraction peaks selected from about 7.4, 23.6, 25.5, 30.1 and 30.5° 2θ measured by CuKα radiation.
4. The compound according to claim 1 , wherein the compound is characterized by a thermal event at about 125° C., as measured by differential scanning calorimetry.
5. The compound according to claim 1 , characterized by a weight loss of about 9.5% to about 14% from about 100° C. through about 200° C., as measured by thermal gravimetric analysis.
6. The compound according to claim 1 , wherein the compound is characterized by single crystal parameters of about
a=9.2228 (15) Å;
b=12.283 (2) Å;
c=14.587 (2) Å;
α=84.923° (8°), β=82.932 (8°), γ=70.753 (8°).
7. The compound according to claim 1 , wherein the cell volume is about 1546.3 Å3.
8. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound according to claim 1 and pharmaceutically acceptable excipient.
9. A method of preparing the compound according to claim 1 , comprising:
a. dissolving ponatinib freebase in a mixture of acetic acid and ethyl acetate or a mixture of acetic acid, methanol and ethyl acetate to yield a solution;
b. adding hydrochloride in an organic solvent to the solution; and
c. cooling the solution to precipitate the acetic acid solvated hydrate of ponatinib hydrochloride.
10. The method of claim 9 , wherein the molar ratio of ponatinib to hydrochloride is about 1:1.
11. The method of claim 9 , wherein the organic solvent is isopropyl alcohol, ethyl acetate, 2-pentanol, or any mixture thereof.
12. The method of claim 9 , wherein the precipitate is rinsed with a solvent selected from the group consisting of isopropyl alcohol, heptane, ethyl acetate, toluene or 2-pentanol.
13. The method of claim 12 , wherein the solvent is isopropyl alcohol, heptane or ethyl acetate.
14. The method of claim 9 , wherein step b is carried out at about 50° C.
15. The method of claim 9 , wherein the cooling is to at least about 0° C.
16. A method of preparing the compound according to claim 1 , comprising:
a. dissolving ponatinib freebase in a mixture of acetic acid and ethyl acetate to yield a solution;
b. adding aqueous hydrochloride dissolved in isopropyl alcohol to the solution; and
c. cooling the solution to about 0° C. to yield a precipitate comprising the acetic acid solvated hydrate of ponatinib hydrochloride.