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.
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19 . 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
at least one saturated hydrocarbon,
wherein the pharmaceutical composition is in the form of an ointment.
20 . The pharmaceutical composition of claim 19 , wherein the at least one saturated hydrocarbon is chosen from mineral oil, hydrogenated castor oil, and combinations thereof.
21 . The pharmaceutical composition of claim 19 , wherein the at least one compound is suspended in the ointment.
22 . The pharmaceutical composition of claim 19 , further comprising at least one viscosity modifier.
23 . The pharmaceutical composition of claim 22 , wherein the pharmaceutical composition comprises about 0.1% to about 20% by weight of the at least one viscosity modifier.
24 . The pharmaceutical composition of claim 22 , wherein the at least one viscosity modifier is microcrystalline wax.
25 . The pharmaceutical composition of claim 19 , further comprising at least one dispersing agent.
26 . The pharmaceutical composition of claim 25 , wherein the pharmaceutical composition comprises about 0.01% to about 30% by weight of the at least one dispersing agent.
27 . The pharmaceutical composition of claim 25 , wherein the at least one dispersing agent is chosen from dimethicone, medium chain triglycerides, and combinations thereof.
28 . The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition comprises:
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.
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43 . The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition comprises about 0.1% to about 10% by weight of the at least one compound.
44 . The pharmaceutical composition of claim 43 , wherein the pharmaceutical composition comprises at least about 0.5% by weight of the at least one compound.
45 . The pharmaceutical composition of claim 43 , wherein the pharmaceutical composition comprises about 1% by weight of the at least one compound.
46 . The pharmaceutical composition of claim 43 , wherein the pharmaceutical composition comprises about 2% by weight of the at least one compound.
47 . The pharmaceutical composition of claim 46 , 46 , 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.
48 . The pharmaceutical composition of claim 47 , wherein at least about 95% by weight of the at least one compound is an (E) isomer.
49 . The pharmaceutical composition of claim 47 , wherein the at least one compound is substantially amorphous.
50 . The pharmaceutical composition of claim 47 , wherein the at least one compound is micronized.
51 . The pharmaceutical composition of claim 50 , wherein the at least one compound has a particle size distribution D90 in the range of about 5 to about 10 microns.
52 . The pharmaceutical composition of claim 19 , wherein the at least one compound is crystalline.
53 . The pharmaceutical composition of claim 52 , wherein the at least one compound is crystalline Form (I).
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55 . The pharmaceutical composition of claim 52 , wherein the at least one compound is crystalline Form (II).
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57 . 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 28 .
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