Topical Pharmaceutical Compositions Comprising 2-[3-[4-Amino-3-(2-Fluoro-4-Phenoxy-Phenyl)-1H-Pyrazolo[3,4-D]Pyrimidin-1-YL]Piperidine-1-Carbonyl]-4,4-Dimethylpent-2-Enenitrile
Disclosed herein are topical pharmaceutical compositions, e.g., for application to the skin of a subject, comprising (R)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile (Compound (I)), methods of making the same, and methods of using the same, e.g., for the treatment of various dermatological disorders.
1 .- 61 . (canceled)
62 . A pharmaceutical composition comprising:
at least one compound chosen from 2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile and pharmaceutically acceptable salts thereof; and
about 0.1% to about 20% by weight of medium chain triglycerides;
about 0.1% to about 20% by weight of microcrystalline wax;
about 0.1% to about 10% by weight of hydrogenated castor oil;
about 0.01% to about 10% by weight of dimethicone; and
Q.S. to 100% of white mineral oil,
wherein the pharmaceutical composition is in the form of an ointment.
63 . The pharmaceutical composition of claim 62 , wherein the pharmaceutical composition comprises about 0.1% to about 10% by weight of the at least one compound.
64 . The pharmaceutical composition of claim 63 , wherein the pharmaceutical composition comprises at least about 0.5% by weight of the at least one compound.
65 . The pharmaceutical composition of claim 62 wherein at least about 95% by weight of the at least one compound is (R)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile.
66 . The pharmaceutical composition of claim 65 , wherein at least about 95% by weight of the at least one compound is an (E) isomer.
67 . The pharmaceutical composition of claim 65 , wherein the at least one compound is substantially amorphous.
68 . The pharmaceutical composition of claim 65 , wherein the at least one compound is micronized.
69 . The pharmaceutical composition of claim 62 , wherein the at least one compound is crystalline.
70 . The pharmaceutical composition of claim 69 , wherein the at least one compound is crystalline Form (I).
71 . The pharmaceutical composition of claim 69 , wherein the at least one compound is crystalline Form (II).
72 . A pharmaceutical composition comprising:
at least one compound chosen from 2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile and pharmaceutically acceptable salts thereof; and
about 1% to about 45% by weight of oleic acid;
about 0.1% to about 20% by weight of glycerin;
about 0.1% to about 45% by weight of propylene glycol;
about 0.1% to about 5% by weight of benzyl alcohol;
about 0.1% to about 5% by weight of a Pemulen™ polymer;
an amount of 10% (w/w) sodium hydroxide solution sufficient to adjust the pH to a value in the range of about 4 to about 6; and
Q.S. to 100% of purified water,
wherein the pharmaceutical composition is in the form of a cream.
73 . The pharmaceutical composition of claim 72 , wherein the pharmaceutical composition comprises about 0.1% to about 10% by weight of the at least one compound.
74 . The pharmaceutical composition of claim 72 , wherein the pharmaceutical composition comprises at least about 0.5% by weight of the at least one compound.
75 . The pharmaceutical composition of claim 72 wherein at least about 95% by weight of the at least one compound is (R)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile.
76 . The pharmaceutical composition of claim 72 , wherein at least about 95% by weight of the at least one compound is an (E) isomer.
77 . The pharmaceutical composition of claim 75 , wherein the at least one compound is substantially amorphous.
78 . The pharmaceutical composition of claim 75 , wherein the at least one compound is micronized.
79 . The pharmaceutical composition of claim 72 , wherein the at least one compound is crystalline.
80 . The pharmaceutical composition of claim 79 , wherein the at least one compound is crystalline Form (I).
81 . The pharmaceutical composition of claim 79 , wherein the at least one compound is crystalline Form (II).
82 . A method of treating a dermatological disorder in a mammal in need thereof, the method comprising topically administering to at least a portion of the skin of the subject of the mammal at least one topical pharmaceutical composition of claim 62 .