Solid state forms of ibrutinib
The present invention encompasses solid state forms of Ibrutinib, including forms G, J and K, and pharmaceutical compositions thereof.
1. A crystalline form of Ibrutinib designated as form G, characterized by data selected from one or more of the following: X-ray diffraction pattern having peaks at 5.6, 10.6, 14.1, 16.5 and 19.4 degrees 2-theta±0.2 degrees 2-theta; X-ray diffraction pattern having peaks at 12.6, 15.8, 16.5, 19.4 and 22.7 degrees 2-theta±0.2 degrees 2-theta; an X-ray powder diffraction pattern as depicted in FIG. 1 ; or combinations of these data.
2. A crystalline form of Ibrutinib designated as form G, characterized by an X-ray diffraction pattern having peaks at 5.6, 10.6, 14.1, 16.5 and 19.4 degrees 2-theta±0.2 degrees 2-theta, and further characterized by having one, two, three, four, or five additional peaks selected from: 12.6, 15.8, 21.1, 21.6 and 22.7 degrees 2-theta±0.2 degrees 2-theta.
3. A crystalline form of Ibrutinib designated as form G, characterized by an X-ray diffraction pattern having peaks at 12.6, 15.8, 16.5, 19.4 and 22.7 degrees 2-theta±0.2 degrees 2-theta and further characterized by having one, two, three, four, or five additional peaks selected from 5.6, 10.6, 14.1, 21.1 and 21.6 degrees 2-theta±0.2 degrees 2-theta.
4. The crystalline form G according to claim 1 , wherein said form is a solvated form.
5. The crystalline form G according to claim 1 , wherein form G is an acetic acid solvate.
6. The crystalline form G according to claim 5 wherein form G is also hydrated.
7. The crystalline form G according to claim 1 , further characterized by a chemical purity of at least 99.5%.
8. A pharmaceutical formulation comprising Ibrutinib form G as defined in claim 1 and at least one pharmaceutically acceptable excipient.
9. A process for preparing other solid state forms of Ibrutinib, salts of Ibrutinib, and/or pharmaceutical compositions thereof, comprising preparing form G as defined in claim 1 and converting it to the desired solid state form or salt of Ibrutinib.
10. A process for preparing Ibrutinib form G as defined in claim 1 , comprising obtaining a reaction mixture of ibrutinib in acetic acid and precipitating Ibrutinib form G.
11. The process of claim 10 , wherein the reaction mixture comprises an organic solvent, water or mixture thereof.
12. A process for preparing the pharmaceutical formulation according to claim 8 comprising combining Ibrutinib form G as defined in claim 1 , with at least one pharmaceutically acceptable excipient.
13. A method for treating cancer in a subject in need thereof, said method comprising the step of administering to said subject a therapeutically effective amount of Ibrutinib form G as defined in claim 1 or a pharmaceutical formulation thereof comprising the therapeutically effective amount Ibrutinib form G as defined in claim 1 and at least one pharmaceutically acceptable excipient.
14. The method for treating cancer according to claim 13 , wherein said cancer is B-cell lymphoma.