Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid

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 disintegrant, a surfactant, a binder, 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. Processes of preparing pharmaceutical compositions comprising Compound 1 are also disclosed.

1 - 52 . (canceled) 
     
     
         53 . A continuous process for preparing a tablet comprising 3-(6-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid, comprising the steps of:
 a) mixing 3-(6-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid, a filler, and a disintegrant in a blender to form a blend;   b) preparing a granulation solution with water, a binder, and a surfactant;   c) feeding the blend from step a) into a continuous twin screw granulator while adding the granulation solution from step b) to produce granules;   d) drying the granules from step c) and milling them;   e) blending the milled granules from step d) with a filler, disintegrant, and lubricant to form a blend;   f) compressing the blend from step e) into a tablet; and   g) optionally coating the tablet from step f).   
     
     
         54 . The process of  claim 53 , wherein 3-(6-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is in Form I, wherein the Form I is characterized by one or more peaks at 15.2 to 15.6 degrees, 16.1 to 16.5 degreees, and 14.3 to 14.7 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation. 
     
     
         55 . The process of claims  1  and  2 , wherein the tablet further comprises N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide. 
     
     
         56 . A tablet prepared by the process of any one of  claims 53 - 55 . 
     
     
         57 . A method of treating cystic fibrosis comprising administering a tablet comprising 3-(6-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid prepared by the process of any one of  claims 53 - 55 .