Pharmaceutical formulations of a Bruton's tyrosine kinase inhibitor
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.
1. A solid tablet formulation comprising ibrutinib and pharmaceutically acceptable excipients, wherein the ibrutinib is a compound with the structure of Compound 1,
and wherein the solid tablet formulation comprises about 60% w/w to about 75% w/w of the ibrutinib, and the excipients comprise:
one or more diluents selected from group consisting of: lactose, sucrose, dextrose, dextrates, maltodextrin, mannitol, xylitol, sorbitol, cyclodextrins, calcium phosphate, calcium sulfate, starches, modified starches, cellulose, microcrystalline cellulose, microcellulose, and talc;
one or more disintegrating agents selected from the group consisting of: natural starch, a pregelatinized starch, a sodium starch, methylcrystalline cellulose, methylcellulose, croscarmellose, croscarmellose sodium, crosslinked sodium carboxymethylcellulose, cross-linked carboxymethylcellulose, cross-linked croscarmellose, cross-linked starch, cross-linked polymer, cross-linked polyvinylpyrrolidone, sodium alginate, a clay, and a gum;
one or more binders selected from the group consisting of: hydroxypropyl cellulose, and polyvinylpyrrolidone;
colloidal silicon dioxide; and
magnesium stearate.
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,
and wherein the solid tablet formulation comprises about 60% w/w to about 75% w/w of ibrutinib, and the excipients comprise:
microcrystalline cellulose in an amount from about 1% w/w to about 20% w/w;
croscarmellose sodium in an amount from about 1% w/w to about 10% w/w;
crospovidone in an amount from about 5% w/w to about 15% w/w;
polyvinylpyrrolidone in an amount from about 1% w/w to about 5% w/w;
sodium lauryl sulfate in an amount from about 0% w/w to about 10% w/w;
colloidal silicon dioxide in an amount from about 0.1% w/w to about 1.5% w/w; and
magnesium stearate in an amount from about 0.01% w/w to about 5% w/w.
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,
about 60% w/w to about 75% w/w of the ibrutinib,
wherein the excipients comprise intragranular and extragranular excipients; wherein the intragranular excipients comprise microcrystalline cellulose and polyvinylpyrrolidone; and
wherein extragranular excipients comprise croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate.
25. The solid tablet formulation of claim 24 , wherein the extragranular excipients further comprise microcrystalline cellulose.