The PCT application WO2016/185490 discloses a compound of Formula I (cyclopropanecarboxylic acid (5-{5-[N-(2-chloro-6-methylbenzoyl) hydrazinocarbonyl]-2-methyl-phenylethynyl}-pyridin-2-yl)amide).



FIELD OF INVENTION

The present invention relates to amorphous dispersion of cyclopropanecarboxylic acid (5-{5-[N′-(2-chloro-6-methylbenzoyl) hydrazinocarbonyl]-2-methyl-phenylethynyl}-pyridin-2-yl)amide.

BACKGROUND OF THE INVENTION

Compound of Formula I is a potent inhibitor of Abl tyrosine kinase. Conventional oral solid dosage forms of compound of Formula I failed to provide adequate bioavailability. There remains a need to provide the compound of formula I in a bioavailable form. There is a need for an oral solid dosage form of the compound of formula I that has adequate bioavailability and stability.

SUMMARY OF THE INVENTION

The present inventors have discovered novel amorphous dispersion of compound of Formula I in a fusible polymeric carrier and oral, solid dosage form comprising the amorphous dispersion. The oral, solid dosage form of the amorphous dispersion provides enhanced bioavailability as well as stability.

In a preferred embodiment, the present invention provides an oral, solid dosage form comprising a mixture of a compound of formula I


and a fusible polymeric carrier, wherein the mixture is an amorphous dispersion. The oral, solid dosage form optionally comprises of pharmaceutically acceptable excipients. The amorphous dispersion in the oral solid dosage form of the invention is physically and chemically stable during melt processing and the oral, solid dosage form remains stable on storage. Particularly, when the oral dosage form is stored at 40° C. and 75% relative humidity for 6 months, each of the degradation impurity such as stage IV impurity and amine impurity is less than 0.2% by weight of the compound of formula I and the total impurity, which is a sum of known and unknown impurities, is less than 2% by weight of the compound of formula I. Further, the compound of formula I remains in the amorphous state during the period of storage.

