Pharmaceutical formulations of a Bruton's tyrosine kinase inhibitor

• US 10,828,259 B2
• Filed: 04/10/2020
• Issued: 11/10/2020
• Est. Priority Date: 03/03/2015
• Status: Active Grant

• Current Assignee: Pharmacyclics LLC (Abbvie Incorporated)
• Original Assignee: Pharmacyclics LLC (Abbvie Incorporated)
• Inventors: Chong, Ching W., Kuehl, Robert, Tan, Heow, Atluri, Harisha
• Primary Examiner(s): Murray, Jeffrey H
• Application Number:
  US16/846,064
• Publication Number:
  US 20200237673A1
• Time in Patent Office: 214 Days
• Field of Search: 5142621, 544262
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Described herein are pharmaceutical formulations of 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. Also disclosed are 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.

Claims

1. A solid tablet formulation comprising ibrutinib and pharmaceutically acceptable excipients, wherein the ibrutinib is a compound with the structure of Compound 1,

2. The solid tablet formulation of claim 1, wherein the one or more disintegrating agents are selected from the group consisting of croscarmellose sodium, and crospovidone.

3. The solid tablet formulation of claim 1, wherein the diluent is microcrystalline cellulose.

4. The solid tablet formulation of claim 1, wherein the binder is polyvinylpyrrolidone.

5. The solid tablet formulation of claim 1, wherein the excipients comprise microcrystalline cellulose, crospovidone, polyvinylpyrrolidone, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate.

6. The solid tablet formulation of claim 1, wherein the colloidal silicon dioxide is present in an amount from about 0.1% w/w to about 1.5% w/w.

7. The solid tablet formulation of claim 1, wherein the magnesium stearate is present in an amount from about 0.01% w/w to about 5% w/w.

8. The solid tablet formulation of claim 1, wherein the magnesium stearate is present in an amount from about 0.01% w/w to about 2% w/w.

9. The solid tablet formulation of claim 1, wherein the magnesium stearate is present in an amount from about 0.1% w/w to about 0.7% w/w.

10. A solid tablet formulation comprising ibrutinib and pharmaceutically acceptable excipients, wherein the ibrutinib is a compound with the structure of Compound 1,

11. The solid tablet formulation of claim 10, wherein the microcrystalline cellulose is present in an amount from about 1% w/w to about 10% w/w.

12. The solid tablet formulation of claim 10, wherein the microcrystalline cellulose is present in an amount from about 5% w/w to about 20% w/w.

13. The solid tablet formulation of claim 10, wherein the microcrystalline cellulose is present in an amount from about 8% w/w to about 20% w/w.

14. The solid tablet formulation of claim 10, wherein the microcrystalline cellulose is present in an amount from about 8% w/w to about 15% w/w.

15. The solid tablet formulation of claim 10, wherein the croscarmellose sodium is present in an amount from about 5% w/w to about 10% w/w.

16. The solid tablet formulation of claim 10, wherein the polyvinylpyrrolidone is present in an amount from about 1% w/w to about 3% w/w.

17. The solid tablet formulation of claim 10, wherein the sodium lauryl sulfate is present in an amount from about 0.5% w/w to about 5% w/w.

18. The solid tablet formulation of claim 10, wherein the colloidal silicon dioxide is present in an amount from about 0.4% w/w to about 0.8% w/w.

19. The solid tablet formulation of claim 10, wherein the magnesium stearate is present in an amount from about w/w 0.1% w/w to about 1.5% w/w.

20. The solid tablet formulation of claim 10, wherein the magnesium stearate is present in an amount from about 0.01% w/w to about 2% w/w.

21. The solid tablet formulation of claim 10, wherein the magnesium stearate is present in an amount from about 0.1% w/w to about 0.7% w/w.

22. The solid tablet formulation of claim 10, wherein the microcrystalline cellulose is present in an amount from about 1% w/w to about 10% w/w;

wherein the croscarmellose sodium is present in an amount from about 5% w/w to about 10% w/w;

wherein the polyvinylpyrrolidone is present in an amount from about 1% w/w to about 3% w/w; and

wherein the magnesium stearate is present in an amount from about w/w 0.01% w/w to about 5% w/w.

23. The solid tablet formulation of claim 10, wherein ibrutinib is present in an amount of about 140 mg, about 280 mg, about 420 mg, or about 560 mg.

24. A solid tablet formulation comprising ibrutinib and pharmaceutically acceptable excipients, wherein ibrutinib is a compound with the structure of Compound 1,

25. The solid tablet formulation of claim 24, wherein the extragranular excipients further comprise microcrystalline cellulose.