Tablet compositions

Abstract

Provided herein is a tablet comprising 2-methyl-1-[(4-[-6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol or a pharmaceutically acceptable salt thereof.

What is claimed: 
     
         1 . A tablet comprising, as an active ingredient, 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol having the following formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof (Compound 1), wherein Compound 1 is present in an amount from about 15% to about 40% by weight based on total weight of the tablet, an intragranular excipient and an extragranular excipient, wherein the extragranular excipient comprises from about 5% to about 50% microcrystalline cellulose by weight based on total weight of the tablet. 
     
     
         2 . The tablet of  claim 1 , wherein Compound 1 is present in an amount from about 20% to about 30% by weight based on total weight of the tablet. 
     
     
         3 . The tablet of  claim 1 , wherein Compound 1 is present in an amount of about 20%, 25% or 30% by weight based on total weight of the tablet. 
     
     
         4 . The tablet of  claim 1 , wherein the intragranular excipient comprises from about 30% to about 45% microcrystalline cellulose by weight based on total weight of the tablet. 
     
     
         5 . The tablet of  claim 1 , wherein the intragranular excipient comprises about 34.50%, 44.50% or 39.50% microcrystalline cellulose by weight based on total weight of the tablet. 
     
     
         6 . The tablet of  claim 1 , wherein the extragranular excipient comprises from about 5% to about 25% microcrystalline cellulose by weight based on total weight of the tablet. 
     
     
         7 . The tablet of  claim 1 , wherein the extragranular comprises about 20 microcrystalline cellulose by weight based on total weight of the tablet excipient. 
     
     
         8 . The tablet of  claim 1 , wherein the intragranular excipient comprises a binder, a disintegrant, a wetting agent, a lubricant, a glidant and stabilizer. 
     
     
         9 . The tablet of  claim 1 , wherein the intragranular excipient comprises microcrystalline cellulose, hydroxypropyl cellulose, sodium starch glycolate, sodium lauryl sulfate, magnesium stearate, colloidal silicon dioxide and hypromellose acetate succinate. 
     
     
         10 . The tablet of  claim 9 , wherein intragranular microcrystalline cellulose is present in an amount from about 30% to about 50% by weight based on total weight of the tablet, intragranular hydroxypropyl cellulose is present from about 1.5% to 2.5% by weight based on total weight of the tablet and intragranular sodium starch glycolate is present in an amount from about 5 to about 7% by weight based on total weight of the tablet. 
     
     
         11 . The tablet of  claim 1 , wherein the intragranular excipient comprises about 34.5%, 44,5% or about 39.5% microcrystalline cellulose by weight based on total weight of the tablet, about 2% hydroxypropyl cellulose by weight based on total weight of the tablet and 6%, and sodium starch glycolate by weight based on total weight of the tablet. 
     
     
         12 . The tablet of  claim 1 , wherein the extragranular excipient comprises a diluent, a binder, a disintegrant, a lubricant and a glidant. 
     
     
         13 . The tablet of  claim 1 , wherein the extragranular excipient comprises microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide and magnesium stearate. 
     
     
         14 . The tablet of  claim 13 , wherein extragranular microcrystalline cellulose is present in an amount from about 5% to about 25% by weight based on total weight of the tablet and sodium starch glycolate is present in an amount from about 1.5 to about 3% by weight based on total weight of the tablet. 
     
     
         15 . The tablet of  claim 13 , wherein the extragranular excipient comprises about 20% microcrystalline cellulose by weight based on total weight of the tablet and about 2%, sodium starch glycolate by weight based on total weight of the tablet. 
     
     
         16 . The tablet of  claim 1 , comprising a) Compound 1 in an amount from about 20% to about 30%; b) an intragranular excipient selected from microcrystalline cellulose in an amount of about 34.5%, 44.5% and 39.5%, hydroxypropyl cellulose in an amount of about 2%, sodium starch glycolate in an amount of about 6%; and c) an extragranular excipient selected from about 20% microcrystalline cellulose and about 2%, sodium starch glycolate by weight based on total weight of the tablet. 
     
     
         17 . The tablet of  claim 1 , wherein the tablet comprises 25, 50, 100, 150, or 200 mg of Compound 1. 
     
     
         18 . The tablet of  claim 1 , wherein Compound 1 is 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol. 
     
     
         19 . The tablet of  claim 1 , wherein Compound 1 is 2-methyl-1-[(4-[6-trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate. 
     
     
         20 . The tablet of  claim 1 , wherein Compound 1 is polymorph Form 3 of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate. 
     
     
         21 . The tablet of  claim 20 , wherein Compound 1 further comprises ≤10% amorphous 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl)amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate, 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol or a mixture thereof. 
     
     
         22 . The tablet of  claim 1 , wherein the tablet is a coated tablet. 
     
     
         23 . The tablet of  claim 1 , wherein the tablet comprises Compound 1, colloidal silicon dioxide, hydroxypropyl cellulose, hypromellose acetate succinate, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium laurel sulfate, sodium starch glycolate, talc, and titanium dioxide. 
     
     
         24 . The tablet of  claim 23 , wherein Compound 1 is 2-methyl-1-[(4[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol. 
     
     
         25 . The tablet of  claim 23 , wherein Compound 1 is 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate. 
     
     
         26 . The tablet of  claim 23 , wherein Compound 1 is polymorph Form 3 of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2,-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate. 
     
     
         27 . A method for preparing the tablet of  claim 1 , wherein the method comprises blending Compound 1 with an intragranular excipient and an extragranular excipient and compressing with a bead matte finish punch. 
     
     
         28 . The method of  claim 27 , wherein the intragranular excipient is selected from microcrystalline cellulose, hydroxypropyl cellulose, sodium starch glycolate, sodium lauryl sulfate, magnesium stearate, colloidal silicon dioxide and hypromellose acetate succinate. 
     
     
         29 . The method of  claim 27 , wherein the extragranular excipient is selected from microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide and magnesium stearate. 
     
     
         30 . A method of treating a proliferative disease comprising administering to a subject in need thereof the tablet of  claim 1 . 
     
     
         31 . The method of  claim 30 , wherein the proliferative disease is cancer. 
     
     
         32 . The method of  claim 30 , wherein the proliferative disease is selected from glioma, melanoma, chondrosarcoma, acute myelogenous leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, lymphoma and myeloproliferative neoplasm, each characterized by the presence of a mutant allele of IDH2. 
     
     
         33 . The method of  claim 30 , wherein the proliferative disease is acute myelogenous leukemia characterized by the presence of a mutant allele of IDH2. 
     
     
         34 . The method of  claim 30 , wherein the proliferative disease is relapsed or refractory acute myelogenous leukemia characterized by the presence of a mutant allele of IDH2.