Crystalline forms of a bruton's tyrosine kinase inhibitor

1. A method of making a pharmaceutical formulation of crystalline Form A of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, comprising:

mixing one or more excipients with crystalline Form A of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one having an X-ray powder diffraction (XRPD) pattern comprising 2-Theta peaks at 5.7±0.1°, 18.9±0.1°, and 21.3±0.1°.

2. The method of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern further comprises a 2-Theta peak at 16.1±0.1°.

3. The method of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern further comprises a 2-Theta peak at 13.6±0.10°.

4. The method of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern further comprises a 2-Theta peak at 21.6±0.1°.

5. The method of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern further comprises 2-Theta peaks at 13.6±0.1° and 16.1±0.1°.

6. The method of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern further comprises 2-Theta peaks at 13.6±0.1° and 21.6±0.1°.

7. The method of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern further comprises 2-Theta peaks at 16.1±0.1° and 21.6±0.1°.

8. The method of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern further comprises 2-Theta peaks at 13.6±0.1°, 16.1±0.1°, and 21.6±0.1°.

9. The method of claim 1 , wherein the crystalline form has Infrared (IR) spectrum weak peaks at about 1584 cm −1 , about 1240 cm −1 , about 1147 cm −1 , about 1134 cm −1 , about 1099 cm −1 , and about 1067 cm 1 .

10. The method of claim 1 , wherein the crystalline Form A has a DSC thermogram with an endotherm having an onset at about 154° C. and a peak at about 157° C. and an exotherm at about 159° C.

11. The method of claim 1 , wherein one or more of the excipients is a solid excipient.

12. The method of claim 1 , wherein one or more of the excipients is a diluent.

13. The method of claim 12 , wherein the diluent is selected from the group consisting of lactose, sucrose, dextrose, dextrates, maltodextrin, mannitol, xylitol, sorbitol, cyclodextrins, calcium phosphate, calcium sulfate, starches, modified starches, microcrystalline cellulose, microcellulose, and talc.

14. The method of claim 12 , wherein the diluent is microcrystalline cellulose.

15. The method of claim 1 , wherein one or more of the excipients is a disintegrating agent.

16. The method of claim 15 , wherein the disintegrating agent is selected from the group consisting of natural starch, a pregelatinized starch, a sodium starch, methylcrystalline cellulose, methylcellulose, croscarmellose, croscarmellose sodium, cross-linked sodium carboxymethylcellulose, cross-linked carboxymethylcellulose, cross-linked croscarmellose, cross-linked starch, cross-linked polymer, cross-linked polyvinylpyrrolidone, sodium alginate, a clay, and a gum.

17. The method of claim 15 , wherein the disintegrating agent is croscarmellose sodium.

18. The method of claim 1 , wherein one or more of the excipients is a surfactant.

19. The method of claim 18 , wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, sorbitan monooleate, polyoxyethylene sorbitan monooleate, polysorbates, poloxamers, bile salts, glyceryl monostearate, and copolymers of ethylene oxide and propylene oxide.

20. The method of claim 18 , wherein the surfactant is sodium lauryl sulfate.

21. The method of claim 1 , wherein one or more of the excipients is a lubricant.

22. The method of claim 21 , wherein the lubricant is selected from the group consisting of stearic acid, calcium hydroxide, talc, corn starch, sodium stearyl fumarate, sodium stearate, magnesium stearate, zinc stearate, and waxes.

23. The method of claim 21 , wherein the lubricant is magnesium stearate.

24. The method of claim 1 , further comprising grinding the mixture of one or more excipients and crystalline Form A.

25. The method of claim 1 , further comprising placing the mixture of one or more excipients and crystalline Form A in a gelatin capsule.

26. The method of claim 1 , further comprising placing the mixture of one or more excipients and crystalline Form A in a non-gelatin capsule.

27. The method of claim 1 , wherein the pharmaceutical formulation is in a hard gelatin capsule.

28. A method of making a pharmaceutical formulation of crystalline Form A of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, comprising:

mixing excipients with crystalline Form A of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one having an X-ray powder diffraction (XRPD) pattern comprising 2-Theta peaks at 5.7±0.1°, 18.9±0.1°, and 21.3±0.1°; wherein the excipients are a diluent, a disintegrating agent, a surfactant, and a lubricant.

29. The method of claim 28 , wherein the crystalline form A is mixed with the following excipients:

(a) microcrystalline cellulose;

(b) croscarmellose sodium;

(c) sodium lauryl sulfate; and

(d) magnesium stearate.

30. The method of claim 28 , wherein about 40 wt % to about 50 wt % of crystalline Form A is mixed with the following excipients:

(a) about 40 wt % to about 50 wt % of microcrystalline cellulose;

(b) about 3 wt % to about 10 wt % of croscarmellose sodium;

(c) about 2 wt % to about 7 wt % of sodium lauryl sulfate; and

(d) about 0.2 wt % to about 1.0 wt % of magnesium stearate.

31. The method of claim 1 , wherein about 40 wt % to about 50 wt % of crystalline Form A is mixed with the following excipients

(a) about 40 wt % to about 50 wt % of microcrystalline cellulose;

(b) about 3 wt % to about 10 wt % of croscarmellose sodium;

(c) about 2 wt % to about 7 wt % of sodium lauryl sulfate; and

(d) about 0.2 wt % to about 1.0 wt % of magnesium stearate.