Crystalline forms of a brutons tyrosine kinase inhibitor

Patent metadata

Field	Value
Publication number	US-10752634-B2
Application number	US-202016837665-A
Country	US
Kind code	B2
Filing date	Apr 1, 2020
Priority date	Jun 4, 2012
Publication date	Aug 25, 2020
Grant date	Aug 25, 2020

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

The invntion claimed is:

1. A pharmaceutical formulation for oral administration comprising:
(a) 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;
(b) one or more diluents;
(c) one or more surfactants; and
(d) one or more lubricants.

2. The pharmaceutical formulation of claim 1 , comprising about 20 wt % to about 70 wt % of one or more diluents.

3. The pharmaceutical formulation of claim 1 , comprising about 2 wt % to about 7 wt % of one or more surfactants.

4. The pharmaceutical formulation of claim 1 , comprising:
(a) 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;
(b) about 20 wt % to about 70 wt % of one or more diluents;
(c) about 2 wt % to about 7 wt % of one or more surfactants; and
(d) one or more lubricants.

5. The pharmaceutical formulation of claim 4 , wherein the formulation is in the form of a hard gelatin capsule.

6. The pharmaceutical formulation of claim 4 , 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.

7. The pharmaceutical formulation of claim 4 , 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.

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

9. The pharmaceutical formulation of claim 4 , wherein the one or more diluents is microcrystalline cellulose.

10. The pharmaceutical formulation of claim 4 , 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.

11. The pharmaceutical formulation of claim 4 , 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.

12. The pharmaceutical formulation of claim 4 , 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.

13. The pharmaceutical formulation of claim 4 , wherein the one or more surfactants is sodium lauryl sulfate.

14. The pharmaceutical formulation of claim 4 , wherein the one or more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, magnesium stearate, and zinc stearate.

15. The pharmaceutical formulation of claim 4 , wherein the one or more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, and magnesium stearate.

16. The pharmaceutical formulation of claim 4 , wherein the one or more lubricants are selected from the group consisting of stearic acid, calcium hydroxide, talc, corn starch, sodium stearyl fumarate, sodium stearates, magnesium stearate, zinc stearate, and waxes.

17. The pharmaceutical formulation of claim 4 , wherein the one or more lubricants is magnesium stearate.

18. The pharmaceutical formulation of claim 4 , wherein the formulation further comprises one or more disintegrating agents.

19. The pharmaceutical formulation of claim 18 , 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.

20. The pharmaceutical formulation of claim 18 , 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.

21. The pharmaceutical formulation of claim 18 , 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.

22. The pharmaceutical formulation of claim 18 , wherein the one or more disintegrating agents is croscarmellose sodium.

23. The pharmaceutical formulation of claim 4 , wherein:
a) 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;
b) 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; and
c) the one or 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 4 , wherein:
a) 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;
b) the one or more surfactants are selected from the group consisting of sodium lauryl sulfate, poloxamers, and copolymers of ethylene oxide and propylene oxide; and
c) the one or more lubricants are selected from the group consisting of stearic acid, calcium hydroxide, talc, corn starch, sodium stearyl fumarate, sodium stearates, magnesium stearate, zinc stearate, and waxes.

25. The pharmaceutical formulation of claim 4 , wherein:
a) the one or more diluents is microcrystalline cellulose; and
b) the one or more lubricants is magnesium stearate.

26. The pharmaceutical formulation of claim 18 , wherein:
a) 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;
b) 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;
c) the one or more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, magnesium stearate, and zinc stearate; and
d) the one or more disintegrating agents are selected from the group consisting of natural starch, a pregelatinized sta

Assignees

• Pharmacyclics Llc

Inventors

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

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title