Claims for Patent: 10,786,500

Summary for Patent: 10,786,500

Title:	Stable pharmaceutical composition for oral administration
Abstract:	Provided is a stable pharmaceutical composition for oral administration comprising 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide (hereinafter referred to as compound A) or a pharmaceutically acceptable salt thereof, wherein the generation of related substances during storage is inhibited. In the stable pharmaceutical composition for oral administration, the proportion of crystals of compound A or a pharmaceutically acceptable salt thereof is 60% or more with respect to the total amount of compound A or a pharmaceutically acceptable salt thereof.
Inventor(s):	Miyazaki; Masakazu (Tokyo, JP), Ishiba; Ryohei (Tokyo, JP), Takaishi; Yuki (Tokyo, JP), Uejo; Fumiaki (Tokyo, JP)
Assignee:	ASTELLAS PHARMA INC. (Tokyo, JP)
Application Number:	15/741,377
Patent Claims:	1. A pharmaceutical composition for oral administration comprising: 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate, wherein a proportion of crystals of 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate is 62% or more with respect to a total amount of 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate in the pharmaceutical composition; and at least one pharmaceutical additive selected from the group consisting of lactose, D-mannitol, anhydrous dibasic calcium phosphate, calcium stearate, and talc. 2. The pharmaceutical composition according to claim 1, wherein a pharmaceutical additive content is 50% by weight to 90% by weight with respect to a total weight of the pharmaceutical composition. 3. The pharmaceutical composition according to claim 1, wherein the at least one pharmaceutical additive is D-mannitol. 4. The pharmaceutical composition according to claim 1, wherein the at least one pharmaceutical additive is lactose and/or D-mannitol. 5. The pharmaceutical composition according to claim 2, wherein the at least one pharmaceutical additive is D-mannitol. 6. The pharmaceutical composition according to claim 4, wherein a total content of lactose and/or D-mannitol is 50% by weight to 70% by weight with respect to a total weight of the pharmaceutical composition. 7. The pharmaceutical composition according to claim 3, wherein a total content of D-mannitol is 50% by weight to 70% by weight with respect to a total weight of the pharmaceutical composition. 8. The pharmaceutical composition according to any one of claims 1, 2-5, 6, and 7, which is a tablet. 9. A tablet comprising 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate; at least one pharmaceutical additive selected from the group consisting of lactose, D-mannitol, anhydrous dibasic calcium phosphate, calcium stearate, an talc, wherein a total pharmaceutical additive content is from 50% to 90% by weight with respect to a total weight of the tablet, and wherein a proportion of crystals of 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate is 62% or more with respect to a total amount of 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate in the tablet. 10. The tablet according to claim 9, wherein the pharmaceutical additive is lactose and/or D-mannitol. 11. The tablet according to claim 9, wherein the pharmaceutical additive is D-mannitol.