| abstract |
Embodiments of the invention generally relate to formulations, methods, kits and dosage forms for improved stability of an active pharmaceutical ingredient, wherein the active ingredient comprises a compound of the formula (I) wherein X represents N, Y represents H or an optionally substituted C1-C6 alkyl group; R4 represents a morpholine group optionally substituted with a C1-C6 alkyl group; R7 represents a C1-C6 alkyl group optionally substituted with one or more F; R8 'represents a halogen atom; and R6 is (II), wherein R10 is H, C1-C6 alkyl, halogen, CN or CF3; R12 represents H or a halogen atom; R13 represents H, a halogen atom or a C1-C6 alkyl group; and R17 is H, C1-C6 alkyl, C1-C6 alkyl-NH2; and pharmaceutically acceptable salts and free bases thereof, the active ingredient remaining in a substantially amorphous form after storage of the pharmaceutical formulation for a period of time and under predetermined conditions. In one embodiment, the formulations, methods, kits and dosage forms comprising the active pharmaceutical ingredient having improved stability can be used in the treatment of a condition characterized by deregulation of either of the two RAS / pathways. RAF / MEK / ERK and PI3 K / AKT / PTEN / mTOR. |