Pharmaceutical compositions of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid and administration thereof

Abstract

A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a diluent, a disintegrant, a surfactant, a binder, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering an oral pharmaceutical formulation of Compound 1 to the patient.

1 - 55 . (canceled) 
     
     
         56 . A tablet for oral administration comprising:
 a. 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) Form I, wherein the Compound 1 Form I is present in an amount ranging from 25 mg to 250 mg;   b. a filler;   c. a disintegrant which is croscarmellose sodium and is present in an amount of about 6 wt % to about 10 wt % by weight of the tablet;   d. a surfactant;   e. a lubricant; and   f. a binder.   
     
     
         57 . The tablet of  claim 56 , wherein the filler is selected from cellulose, modified cellulose, sodium carboxymethyl cellulose, ethyl cellulose hydroxymethyl cellulose, hydroxypropylcellulose, cellulose acetate, microcrystalline cellulose, dibasic calcium phosphate, sucrose, lactose, corn starch, potato starch, and any combination thereof. 
     
     
         58 . The tablet of  claim 56 , wherein the filler is microcrystalline cellulose (MCC) and is present in the tablet in an amount ranging from 20 wt % to 55 wt % by weight of the tablet. 
     
     
         59 . The tablet of  claim 56 , wherein the surfactant is selected from sodium lauryl sulfate, sodium stearyl fumarate, polyoxyethylene 20 sorbitan mono-oleate, and any combination thereof. 
     
     
         60 . The tablet of  claim 56 , wherein the surfactant is sodium lauryl sulfate and is present in an amount of 0.3 wt % to 2 wt % by weight of the tablet. 
     
     
         61 . The tablet of  claim 56 , wherein the lubricant is selected from magnesium stearate, calcium stearate, zinc stearate, sodium stearate, stearic acid, aluminum stearate, leucine, glyceryl behenate, hydrogenated vegetable oil, and any combination thereof. 
     
     
         62 . The tablet of  claim 56 , wherein the lubricant is magnesium stearate and is present at a concentration of 0.15 wt % to 4.5 wt % by weight of the tablet. 
     
     
         63 . The tablet of  claim 56 , wherein the binder is selected from polyvinylpyrrolidone, dibasic calcium phosphate, sucrose, corn starch, modified cellulose, and any combination thereof. 
     
     
         64 . The tablet of  claim 56 , wherein the polyvinylpyrrolidone is present at a concentration of 1 wt % to 8 wt % by weight of the tablet. 
     
     
         65 . The tablet of  claim 56 , wherein Compound 1 Form I is present in an amount of 30 wt % to 70 wt % by weight of the tablet. 
     
     
         66 . The tablet of  claim 56 , wherein the Compound 1 Form I is present in the tablet in an amount of 200 mg. 
     
     
         67 . The tablet of  claim 56 , wherein the Compound 1 Form I is present in the tablet in an amount of 100 mg. 
     
     
         68 . A method of treating cystic fibrosis in a subject, comprising administering to the subject a tablet of  claim 56 . 
     
     
         69 . The method of  claim 68 , wherein the subject is homozygous for the ΔF508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR). 
     
     
         70 . A method of treating cystic fibrosis in a subject, comprising administering a tablet for oral administration comprising:
 a. 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) Form I wherein the Compound 1 Form I is present in an amount ranging from 25 mg to 250 mg;   b. a filler;   c. a disintegrant;   d. a surfactant which is sodium lauryl sulfate and is present in an amount of 0.3 wt % to 2 wt % by weight of the tablet;   e. a lubricant; and   f. a binder.   
     
     
         71 . The method of  claim 70 , wherein the subject is homozygous for the ΔF508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR). 
     
     
         72 . A method of treating cystic fibrosis in a subject, comprising administering a tablet for oral administration comprising:
 a. 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) Form I wherein the Compound 1 Form I is present in an amount ranging from 25 mg to 250 mg;   b. a filler;   c. a disintegrant;   d. a surfactant;   e. a lubricant; and   f. a binder;   wherein Compound 1 Form I is present in an amount of 30 wt % to 70 wt % by weight of the tablet.   
     
     
         73 . The method of  claim 72 , wherein the subject is homozygous for the ΔF508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR).