Crystalline forms of a bruton's 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 - 13 . (canceled) 
     
     
         14 . A pharmaceutical formulation for oral administration comprising:
 (a) about 140 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 40 wt % to about 50 wt % of one or more diluents; and   (c) about 0.2 wt % to about 1.0 wt % of one or more lubricants.   
     
     
         15 . The pharmaceutical formulation of  claim 14 , wherein the formulation is in the form of a capsule. 
     
     
         16 . The pharmaceutical formulation of  claim 14 , 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. 
     
     
         17 . The pharmaceutical formulation of  claim 14 , 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. 
     
     
         18 . The pharmaceutical formulation of  claim 14 , wherein the one or more diluents are selected from the group consisting of lactose, sucrose, mannitol, calcium phosphate, starches, modified starches, and microcrystalline cellulose. 
     
     
         19 . The pharmaceutical formulation of  claim 14 , wherein the one or more diluent is microcrystalline cellulose. 
     
     
         20 . The pharmaceutical formulation of  claim 14 , wherein the one or more lubricants are selected from the group consisting of stearic acid, calcium hydroxide, talc, corn starch, sodium stearyl fumarate, sodium stearate, magnesium stearate, zinc stearate, and waxes. 
     
     
         21 . The pharmaceutical formulation of  claim 14 , wherein the one or more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, magnesium stearate, and zinc stearate. 
     
     
         22 . The pharmaceutical formulation of  claim 14 , wherein the one or more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, and magnesium stearate. 
     
     
         23 . The pharmaceutical formulation of  claim 14 , wherein the one or more lubricant is magnesium stearate. 
     
     
         24 . The pharmaceutical formulation of  claim 14 , wherein the formulation further comprises one or more disintegrating agents. 
     
     
         25 . The pharmaceutical formulation of  claim 24 , wherein the one or more disintegrating agents are selected from the group consisting of natural starch, a pregelatinized starch, a sodium starch, methylcrystalline cellulose, methylcellulose, croscarmellose, croscarmellose sodium, cross-linked sodium carboxymethylcellulose, cross-linked carboxymethylcellulose, cross-linked croscarmellose, cross-linked starch, cross-linked polymer, cross-linked polyvinylpyrrolidone, sodium alginate, a clay, and a gum. 
     
     
         26 . The pharmaceutical formulation of  claim 24 , wherein the one or more disintegrating agents are selected from the group consisting of natural starch, a pregelatinized starch, a sodium starch, methylcrystalline cellulose, methylcellulose, croscarmellose, croscarmellose sodium, sodium starch glycolate, crospovidone, sodium alginate, a clay, and a gum. 
     
     
         27 . The pharmaceutical formulation of  claim 24 , wherein the one or more disintegrating agents are selected from the group consisting of natural starch, a pregelatinized starch, a sodium starch, methylcrystalline cellulose, croscarmellose, croscarmellose sodium, sodium starch glycolate, and crospovidone. 
     
     
         28 . The pharmaceutical formulation of  claim 24 , wherein the one or more disintegrating agents are selected from the group consisting of croscarmellose sodium, sodium starch glycolate, and crospovidone. 
     
     
         29 . The pharmaceutical formulation of  claim 24 , the one or more disintegrating agent is croscarmellose sodium. 
     
     
         30 . The pharmaceutical formulation of  claim 14 , wherein the formulation further comprises one of more surfactants. 
     
     
         31 . The pharmaceutical formulation of  claim 30 , 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. 
     
     
         32 . The pharmaceutical formulation of  claim 30 , 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. 
     
     
         33 . The pharmaceutical formulation of  claim 30 , 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. 
     
     
         34 . The pharmaceutical formulation of  claim 30 , wherein the one or more surfactant is sodium lauryl sulfate. 
     
     
         35 . The pharmaceutical formulation of  claim 14 , wherein:
 i. 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; and   ii. the one of more lubricants are selected from the group consisting of stearic acid, calcium hydroxide, talc, corn starch, sodium stearyl fumarate, sodium stearate, magnesium stearate, zinc stearate, and waxes.   
     
     
         36 . The pharmaceutical formulation of  claim 35 , wherein the dosage form is a hard gelatin capsule. 
     
     
         37 . The pharmaceutical formulation of  claim 14 , wherein:
 i. 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; and   ii. the one of more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, magnesium stearate, and zinc stearate.   
     
     
         38 . The pharmaceutical formulation of  claim 37 , wherein the dosage form is a hard gelatin capsule. 
     
     
         39 . The pharmaceutical formulation of  claim 14 , wherein:
 i. the one or more diluents are selected from the group consisting of lactose, sucrose, mannitol, calcium phosphate, starches, modified starches, and microcrystalline cellulose; and   ii. the one of more lubricants are selected from the group consisting of stearic acid, talc, sodium stearyl fumarate, and magnesium stearate.   
     
     
         40 . The pharmaceutical formulation of  claim 39 , wherein the dosage form is a hard gelatin capsule. 
     
     
         41 . The pharmaceutical formulation of  claim 14 , wherein:
 i. the one or more diluent is microcrystalline cellulose; and   ii. the one or more lubricant is magnesium stearate.   
     
     
         42 . The pharmaceutical formulation of  claim 14  comprising:
 (a) about 40 wt % to about 50 wt % 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) microcrystalline cellulose; and 
 (c) magnesium stearate. 
 
     
     
         43 . The pharmaceutical formulation of  claim 42 , wherein the dosage form is a hard gelatin capsule.