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

Abstract

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.

What is claimed is: 
     
         1 - 18 . (canceled) 
     
     
         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). 
     
     
         54 . (canceled) 
     
     
         55 . The pharmaceutical composition of  claim 52 , wherein the at least one compound is crystalline Form (II). 
     
     
         56 . (canceled) 
     
     
         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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