Crystalline forms of a Bruton's tyrosine kinase inhibitor

Patent metadata

Field	Value
Publication number	US-10294232-B2
Application number	US-201816111014-A
Country	US
Kind code	B2
Filing date	Aug 23, 2018
Priority date	Jun 4, 2012
Publication date	May 21, 2019
Grant date	May 21, 2019

Abstract

Described herein is the Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including crystalline forms, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

First claim

What is claimed is:

1. A pharmaceutical formulation for oral administration comprising:
(a) about 40 mg to about 200 mg 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;
(b) about 40 wt % to about 50 wt % of one or more diluents;
(c) one or more disintegrating agents; and
(d) about 0.2 wt % to about 1.0 wt % of one or more lubricants.

2. The pharmaceutical formulation of claim 1 , wherein the formulation is in the form of a capsule comprising about 140 mg 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.

3. The pharmaceutical formulation of claim 1 , wherein the one or more diluents are 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.

4. The pharmaceutical formulation of claim 1 , wherein the one or more diluents are selected from the group consisting of lactose, sucrose, dextrose, mannitol, xylitol, sorbitol, calcium phosphate, starches, modified starches, microcrystalline cellulose, and microcellulose.

5. The pharmaceutical formulation of claim 1 , wherein the one or more diluents are selected from the group consisting of lactose, sucrose, mannitol, calcium phosphate, starches, modified starches, and microcrystalline cellulose.

6. The pharmaceutical formulation of claim 1 , wherein the one or more diluent is microcrystalline cellulose.

7. The pharmaceutical formulation of claim 1 , wherein the one or more lubricants are selected from the group consisting of stearic acid, calcium hydroxide, talc, corn starch, sodium stearyl fumarate, sodium stearate, magnesium stearate, zinc stearate, and waxes.

8. The pharmaceutical formulation of claim 1 , wherein the one or more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, magnesium stearate, and zinc stearate.

9. The pharmaceutical formulation of claim 1 , wherein the one or more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, and magnesium stearate.

10. The pharmaceutical formulation of claim 1 , wherein the one or more lubricant is magnesium stearate.

11. The pharmaceutical formulation of claim 1 , wherein the one or more disintegrating agents are 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.

12. The pharmaceutical formulation of claim 1 , wherein the one or more disintegrating agents are selected from the group consisting of natural starch, a pregelatinized starch, a sodium starch, methylcrystalline cellulose, methylcellulose, croscarmellose, croscarmellose sodium, sodium starch glycolate, crospovidone, sodium alginate, a clay, and a gum.

13. The pharmaceutical formulation of claim 1 , wherein the one or more disintegrating agents are selected from the group consisting of natural starch, a pregelatinized starch, a sodium starch, methylcrystalline cellulose, croscarmellose, croscarmellose sodium, sodium starch glycolate, and crospovidone.

14. The pharmaceutical formulation of claim 1 , wherein the one or more disintegrating agents are selected from the group consisting of croscarmellose sodium, sodium starch glycolate, and crospovidone.

15. The pharmaceutical formulation of claim 1 , the one or more disintegrating agent is croscarmellose sodium.

16. The pharmaceutical formulation of claim 1 , wherein the formulation further comprises one of more surfactants.

17. The pharmaceutical formulation of claim 16 , wherein the one or more surfactants are 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.

18. The pharmaceutical formulation of claim 16 , wherein the one or more surfactants are selected from the group consisting of sodium lauryl sulfate, polyoxyethylene sorbitan monooleate, polysorbates, poloxamers, and copolymers of ethylene oxide and propylene oxide.

19. The pharmaceutical formulation of claim 16 , wherein the one or more surfactants are selected from the group consisting of sodium lauryl sulfate, poloxamers, and copolymers of ethylene oxide and propylene oxide.

20. The pharmaceutical formulation of claim 16 , wherein the one or more surfactant is sodium lauryl sulfate.

21. The pharmaceutical formulation of claim 1 , wherein:
i. the one or more diluents are 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; and
ii. the one of more lubricants are selected from the group consisting of stearic acid, calcium hydroxide, talc, corn starch, sodium stearyl fumarate, sodium stearate, magnesium stearate, zinc stearate, and waxes.

22. The pharmaceutical formulation of claim 21 , wherein the dosage form is a hard gelatin capsule.

23. The pharmaceutical formulation of claim 1 , wherein:
i. the one or more diluents are selected from the group consisting of lactose, sucrose, dextrose, mannitol, xylitol, sorbitol, calcium phosphate, starches, modified starches, microcrystalline cellulose, and microcellulose; and
ii. the one of more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, magnesium stearate, and zinc stearate.

24. The pharmaceutical formulation of claim 23 , wherein the dosage form is a hard gelatin capsule.

25. The pharmaceutical formulation of claim 1 , wherein:
i. the one or more diluents are selected from the group consisting of lactose, sucrose, mannitol, calcium phosphate, starches, modified starches, and microcrystalline cellulose; and
ii. the one of more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, and magnesium stearate.

26. The pharmaceutical formulation of claim 25 , wherein the dosage form is a hard gelatin capsule.

27. The pharmaceutical formulation of claim 1 , wherein:
i. the one or more diluent is microcrystalline cellulose; and
ii. the one or more lubricant is magnesium stearate.

28. The pharmaceutical formulation of claim 1 comprising:
(a) about 40 wt % to about 50 wt % 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;
(b) microcrystalline cellulose; and
(c) magnesium stearate.

29. The pharmaceutical formulation of claim 28 , wherein the dosage form is a hard gelatin capsule.

Assignees

• Pharmacyclics Llc

Inventors

• Purro Norbert
• Smyth Mark S
• Goldman Erick
• Wirth David D

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/02

  specific for leukemia · CPC title