Crystalline forms of a brutons tyrosine kinase inhibitor

Abstract

Described herein is the 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, including crystalline forms, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as 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 pharmaceutical formulation for oral administration comprising:
 (a) about 70 mg of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one;   (b) one or more diluents;   (c) one or more surfactants; and   (d) one or more lubricants.   
     
     
         2 . The pharmaceutical formulation of  claim 1 , comprising about 20 wt % to about 70 wt % of one or more diluents. 
     
     
         3 . The pharmaceutical formulation of  claim 1 , comprising about 2 wt % to about 7 wt % of one or more surfactants. 
     
     
         4 . The pharmaceutical formulation of  claim 1 , comprising:
 (a) about 70 mg of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one;   (b) about 20 wt % to about 70 wt % of one or more diluents;   (c) about 2 wt % to about 7 wt % of one or more surfactants; and   (d) one or more lubricants.   
     
     
         5 . The pharmaceutical formulation of  claim 4 , wherein the formulation is in the form of a hard gelatin capsule. 
     
     
         6 . The pharmaceutical formulation of  claim 4 , wherein the one or more diluents are selected from the group consisting of lactose, sucrose, dextrose, dextrates, maltodextrin, mannitol, xylitol, sorbitol, cyclodextrins, calcium phosphate, calcium sulfate, starches, modified starches, microcrystalline cellulose, microcellulose, and talc. 
     
     
         7 . The pharmaceutical formulation of  claim 4 , wherein the one or more diluents are selected from the group consisting of lactose, sucrose, dextrose, mannitol, xylitol, sorbitol, calcium phosphate, starches, modified starches, microcrystalline cellulose, and microcellulose. 
     
     
         8 . The pharmaceutical formulation of  claim 4 , wherein the one or more diluents are selected from the group consisting of lactose, sucrose, mannitol, calcium phosphate, starches, modified starches, and microcrystalline cellulose. 
     
     
         9 . The pharmaceutical formulation of  claim 4 , wherein the one or more diluents is microcrystalline cellulose. 
     
     
         10 . The pharmaceutical formulation of  claim 4 , wherein the one or more surfactants are selected from the group consisting of sodium lauryl sulfate, polyoxyethylene sorbitan monooleate, polysorbates, poloxamers, and copolymers of ethylene oxide and propylene oxide. 
     
     
         11 . The pharmaceutical formulation of  claim 4 , wherein the one or more surfactants are selected from the group consisting of sodium lauryl sulfate, poloxamers, and copolymers of ethylene oxide and propylene oxide. 
     
     
         12 . The pharmaceutical formulation of  claim 4 , wherein the one or more surfactants are selected from the group consisting of sodium lauryl sulfate, sorbitan monooleate, polyoxyethylene sorbitan monooleate, polysorbates, poloxamers, bile salts, glyceryl monostearate, and copolymers of ethylene oxide and propylene oxide. 
     
     
         13 . The pharmaceutical formulation of  claim 4 , wherein the one or more surfactants is sodium lauryl sulfate. 
     
     
         14 . The pharmaceutical formulation of  claim 4 , wherein the one or more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, magnesium stearate, and zinc stearate. 
     
     
         15 . The pharmaceutical formulation of  claim 4 , wherein the one or more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, and magnesium stearate. 
     
     
         16 . The pharmaceutical formulation of  claim 4 , wherein the one or more lubricants are selected from the group consisting of stearic acid, calcium hydroxide, talc, corn starch, sodium stearyl fumarate, sodium stearates, magnesium stearate, zinc stearate, and waxes. 
     
     
         17 . The pharmaceutical formulation of  claim 4 , wherein the one or more lubricants is magnesium stearate. 
     
     
         18 .- 28 . (canceled) 
     
     
         29 . A method of modulating the B-cell signaling pathway in a subject in need thereof, the method comprising administering a therapeutically effective amount of ibrutinib to the subject. 
     
     
         30 . A pharmaceutical composition comprising ibrutinib and one or more pharmaceutically acceptable excipients, adjuvants, diluents, and/or carriers. 
     
     
         31 . A kit comprising the formulation of  claim 1 , and instructions for use.