DRUG FORMULATIONS OF (R)-1-(1-ACRYLOYLPIPERIDIN-3-YL)-4-AMINO-3-(4-PHENOXYPHENYL)-1H-IMIDAZO[4,5-C]PYRIDIN-2(3H)-ONE
This disclosure relates to the field of therapeutic Bruton's tyrosine kinase (BTK) inhibitors. Pharmaceutical formulations of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one are described.
1 . A tablet comprising:
at least one compound chosen from (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one (Compound 1) and pharmaceutically acceptable salts thereof;
at least one diluent;
at least one binder;
at least one disintegrant; and
at least one lubricant.
2 . The tablet of claim 1 , further comprising at least one flow agent.
3 . The tablet of claim 1 , wherein the tablet comprises an intragranular core and an extragranular portion.
4 . The tablet of claim 3 , wherein the at least one diluent is chosen from lactose monohydrate and microcrystalline cellulose.
5 . The tablet of claim 4 , wherein the at least one diluent is present in a total amount ranging from about 70% to about 90% by weight.
6 . The tablet of claim 5 , wherein the at least one diluent is present in the intragranular core in a total amount ranging from about 50% to about 70% by weight.
7 . The tablet of claim 5 , wherein the at least one diluent is present in the extragranular portion in a total amount ranging from about 10% to about 30% by weight.
8 . The tablet of claim 1 , wherein the at least one binder is hydroxypropyl methylcellulose (hypromellose).
9 . The tablet of claim 8 , wherein the at least one binder is present in a total amount ranging from about 0.1% to about 5% by weight.
10 . The tablet of claim 3 , wherein the at least one disintegrant is cross linked polyvinyl N-pyrrolidone (crospovidone).
11 . The tablet of claim 10 , wherein the at least one disintegrant is present in a total amount ranging from about 0.1% to about 5% by weight.
12 . The tablet of claim 11 , wherein the at least one disintegrant is present in the intragranular core in a total amount ranging from about 0.5% to about 3% by weight.
13 . The tablet of claim 11 , wherein the at least one disintegrant is present in the extragranular portion in a total amount ranging from about 0.5% to about 3% by weight.
14 . The tablet of claim 1 , wherein the at least one lubricant is magnesium stearate.
15 . The tablet of claim 14 , wherein the at least one lubricant is present in a total amount ranging from about 0.1% to about 5% by weight.
16 . The tablet of claim 2 , wherein the at least one flow agent is talc.
17 . The tablet of claim 16 , wherein the at least one flow agent is present in a total amount ranging from about 1% to about 5% by weight.
18 . The tablet of claim 3 , wherein the intragranular core comprises at least one diluent, at least one binder, and at least one disintegrant.
19 . The tablet of claim 3 , wherein the extragranular portion comprises at least one diluent, at least one disintegrant, and at least one lubricant.
20 . The tablet of claim 1 , wherein Compound 1 is present in at least 50% crystalline form.
21 . (canceled)
22 . (canceled)
23 . (canceled)
24 . The tablet of claim 1 , wherein Compound 1 is present in an amount of about 60 mg.
25 . The tablet of claim 1 , wherein Compound 1 is present in an amount of about 120 mg.
26 . (canceled)
27 . (canceled)
28 . (canceled)
29 . (canceled)
30 . (canceled)
31 . (canceled)
32 . The tablet of claim 1 , wherein the tablet comprises:
about 15% to about 45% by weight lactose monohydrate,
about 35% to about 60% by weight microcrystalline cellulose,
about 1% to about 5% by weight hydroxypropyl methylcellulose,
about 1% to about 5% by weight crospovidone, and
about 0.1% to about 3% by weight magnesium stearate.
33 . The tablet of claim 32 , wherein the tablet comprises an intragranular core and an extragranular portion.
34 - 88 . (canceled)
89 . A method of treating a disease or condition mediated by BTK in a patient in need thereof, comprising administering to the patient the tablet of claim 1 .
90 . (canceled)