Crystalline forms of ponatinib hydrochloride

Patent metadata

Field	Value
Publication number	US-9725454-B2
Application number	US-201414902790-A
Country	US
Kind code	B2
Filing date	Jul 4, 2014
Priority date	Jul 4, 2013
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

The present disclosure relates to polymorphic forms of the hydrochloride salt of ponatinib (“compound 1”) and to processes for the preparation of these polymorphic forms. The present disclosure also generally relates to a pharmaceutical composition comprising the forms, as well of methods of using the form(s) in the treatment of disorders associated with pathological cellular proliferation, such as neoplasms, and cancer.

First claim

What is claimed is:

1. A solid state form of ponatinib hydrochloride, consisting essentially of crystalline Ponatinib hydrochloride having a x-ray powder diffraction pattern comprising peaks at four or more 2θ values selected from the group consisting of 5.4 ±0.2, 10.0±0.2, 13.35±0.2, 14.07±0.2, 14.83±0.2, 17.57±0.2 and 26.02±0.2° (Cu Kα radiation at 22° C.).

2. The crystalline form of ponatinib hydrochloride according to claim 1 , wherein the content of ICH class 2 solvent is less than 200ppm.

3. The crystalline form of ponatinib hydrochloride according to claim 1 , which can be characterized by a weight loss of at most 0.2% between 25° C. and 125° C.

4. A tablet comprising the crystalline form of ponatinib hydrochloride according to claim 1 , and a pharmaceutically acceptable carrier or diluent.

5. The tablet of claim 4 , which is a film coated tablet.

6. The tablet of claim 5 , wherein the tablet core comprises the crystalline form of ponatinib hydrochloride, lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide and magnesium stearate.

7. A solid state form of ponatinib hydrochloride, comprising a crystalline form having a x-ray powder diffraction pattern comprising peaks at four or more 2θ values selected from the group consisting of 6.21±0.2, 10.58±0.2, 17.03±0.2, 18.62±0.2, 22.02±0.2, 29.13±0.2, 29.47±0.2° (Cu Kα radiation at 22° C.).

8. The crystalline form of ponatinib hydrochloride according to claim 7 , having an X-ray diffraction spectrum substantially the same as the X-ray powder diffraction spectrum shown in FIG. 1 .

9. A composition comprising at least 90 weight % of the crystalline form according to claim 1 , based the weight of the composition.

10. A crystalline form of ponatinib hydrochloride obtainable by slurrying a crystalline form of ponatinib hydrochloride according to claim 7 in a water miscible organic solvent, optionally by slurrying the crystalline form in 2-propanol at 60° C. and stirring the resulting slurry for 48h.

11. The crystalline form of ponatinib hydrochloride according to claim 1 , having an X-ray diffraction spectrum substantially the same as the X-ray powder diffraction spectrum shown in FIG. 2 .

12. The crystalline form of ponatinib hydrochloride according to claim 1 , having a x-ray powder diffraction pattern comprising an additional peak at the 2θ value 6.99±0.2° (Cu Kα radiation at 22° C.).

13. The crystalline form of ponatinib hydrochloride according to claim 10 , further comprising drying under a nitrogen purge to afford the crystalline form.

Assignees

• Sandoz Ag

Inventors

• Stefinovic Marijan
• Reece Hayley
• Sunkara Asha

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/2009

  Inorganic compounds · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title