Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea
Provided herein are low impurity compositions comprising a compound represented by Formula (I): which are useful in the treatment of disorders related to the activity of the c-KIT and PDGFRα kinases, and oncogenic forms thereof.
1. A pharmaceutical solid dispersion composition comprising:
a) a solid dispersion comprising:
hydroxypropyl methyl cellulose acetate succinate; and
50 mg of an amorphous form of a compound represented by Formula (I)
and
b) one or more pharmaceutically acceptable carriers;
wherein:
a compound represented by Formula (II):
is present in the solid dispersion composition in amount of about 0.1% (w/w) to about 0.5% (w/w) by weight based on the total weight of the solid dispersion composition; and
aniline and diphenyl urea are each present in amount equal to or less than about 0.5% by weight based on the total weight of solid dispersion composition.
2. A pharmaceutically acceptable composition for orally delivering 50 mg of a compound represented by Formula (I):
comprising:
a) a solid dispersion having:
50 mg of the compound wherein the compound is present in amorphous form; hydroxypropyl methyl cellulose acetate succinate; and
b) a pharmaceutically acceptable carrier;
wherein a compound represented by Formula (II):
is present in composition in amount equal to or less than about 1.5% by weight based on the total weight of the composition; and
aniline is present in the composition in amount equal to or less than about 0.5% by weight based on the total weight of the composition.
3. A pharmaceutically acceptable composition for orally delivering 50 mg of a compound represented by Formula (I):
comprising:
a solid dispersion having 50 mg of the compound wherein the compound is present in amorphous form, and hydroxypropyl methyl cellulose acetate succinate;
about 25-45% by weight of a bulking agent based on the total amount of the pharmaceutical composition;
about 25-45% by weight of a filler based on the total amount of the pharmaceutical composition; and
a glidant and/or a lubricant; wherein when exposed to 60% relative humidity at 25° C. for 1 month, the composition has not more than about 0.5% (w/w) of a compound represented by Formula (II):