Claims for Patent: 9,555,027

Summary for Patent: 9,555,027

Title:	Pharmaceutical composition
Abstract:	A preparation for oral administration comprising: a pregelatinized starch comprising N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-(2R,3R)-2,3-tetramethyle- ne-butyl]-(1'R,2'S,3'R,4'S)-2,3-bicyclo[2,2,1]-heptanedicarboxyimide hydrochloride (lurasidone) represented by the formula (1) as an active ingredient; a water-soluble excipient; and a water-soluble polymeric binder, the preparation exhibiting an invariant level of elution behavior even when the content of its active ingredient is varied.
Inventor(s):	Fujihara; Kazuyuki (Suzuka, JP)
Assignee:	SUMITOMO DAINIPPON PHARMA CO., LTD. (Osaka, JP)
Application Number:	14/512,189
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,555,027
Patent Claims:	1. An oral preparation, comprising: N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-(2R,3R)-2,3-tetramethyle- ne-butyl]-(1'R,2'S,3'R,4'S)-2,3-bicyclo[2,2,1]heptanedicarboxyimide hydrochloride (lurasidone) of formula (1): ##STR00003## a pregelatinized starch; a water-soluble excipient; and a water-soluble polymer binder, wherein lurasidone is included in the preparation in an amount of from 20 to 45% (wt/wt), and the pregelatinized starch is included in the preparation in an amount of from 10 to 50% (wt/wt). 2. The oral preparation of claim 1, wherein the oral preparation is prepared by a process which comprises granulating a powder mixture comprising lurasidone, a pregelatinized starch and a water-soluble excipient by applying a solution of a water-soluble polymer binder. 3. The oral preparation of claim 1, wherein the oral preparation is prepared by a process which comprises granulating a powder mixture comprising a pregelatinized starch and a water-soluble excipient by a solution or dispersion of lurasidone and a water-soluble polymer binder. 4. The oral preparation of claim 1, wherein the pregelatinized starch is incorporated in an amount of 10 to 40% (wt/wt) based on the weight of the preparation. 5. The oral preparation of claim 1, wherein the pregelatinized starch is incorporated in an amount of 10 to 30% (wt/wt) based on the weight of the preparation. 6. The oral preparation of claim 1, wherein a content of lurasidone in the preparation is 20 to 40% (wt/wt). 7. The oral preparation of claim 1, wherein the water-soluble excipient is at least one selected from the group consisting of mannitol, lactose, saccharose, sorbitol, D-sorbitol, erythritol and xylitol. 8. The oral preparation of claim 1, wherein the water-soluble excipient is mannitol or lactose. 9. The oral preparation of claim 1, wherein a content of the water-soluble excipient per tablet is 30 to 60% (wt/wt). 10. The oral preparation of claim 1, wherein the water-soluble polymer binder is hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone or hydroxypropylcellulose. 11. The oral preparation of claim 1, wherein a content of the water-soluble polymer binder per tablet is 0.5 to 10% (wt/wt). 12. The oral preparation of claim 1, wherein a content of lurasidone per tablet is 10 to 160 mg. 13. The oral preparation of claim 1, wherein a content of lurasidone per tablet is 20 to 120 mg. 14. The oral preparation of claim 1, wherein a content of lurasidone per tablet is 20 to 160 mg. 15. The oral preparation of claim 1, wherein a content of lurasidone per tablet is 40 to 120 mg. 16. The oral preparation of claim 1, wherein the water-soluble excipient is mannitol or lactose, a content of lurasidone in the preparation is 20 to 40% (wt/wt) and the pregelatinized starch is incorporated in an amount of 10 to 40% (wt/wt) based on the weight of the preparation. 17. The oral preparation of claim 1, wherein the water-soluble excipient is mannitol or lactose, a content of lurasidone in the preparation is 20 to 40%, the pregelatinized starch is incorporated in an amount of 10 to 40% (wt/wt) based on the weight of the preparation and a content of lurasidone per tablet is 20 to 120 mg. 18. The oral preparation of claim 1, wherein the water-soluble excipient is mannitol or lactose, a content of lurasidone in the preparation is 20 to 40%, the pregelatinized starch is incorporated in an amount of 10 to 40% (wt/wt) based on the weight of the preparation and a content of lurasidone per tablet is 40 to 120 mg. 19. The oral preparation of claim 1, wherein a pregelatinizing ratio of the pregelatinized starch is 50 to 95%. 20. The oral preparation of claim 1, wherein a 50% by volume particle size of lurasidone is 0.1 to 8 .mu.m. 21. The oral preparation of claim 1, wherein the pregelatinized starch contains water soluble matter of 30% or less. 22. The oral preparation of claim 1, further comprising: a disintegrant, wherein a content of the disintegrant per tablet is 0.5 to 5% (wt/wt). 23. The oral preparation of claim 1, further comprising: a disintegrant, wherein a content of the disintegrant per tablet is 0.5 to 5% (wt/wt); a content of lurasidone in the preparation is 20 to 40%; the pregelatinized starch is incorporated in an amount of 10 to 40% (wt/wt) based on the weight of the preparation; a content of lurasidone per tablet is 40 to 120 mg; a pregelatinizing ratio of the pregelatinized starch is 50 to 95%; 50% by volume particle size of lurasidone is 0.1 to 8 .mu.m; the pregelatinized starch contains water soluble matter of 30% or less; the water-soluble excipient is mannitol or lactose, and a content of the water-soluble excipient per tablet is 30 to 60% (wt/wt); the water-soluble polymer binder is hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone or hydroxypropylcellulose; and a content of the water-soluble polymer binder per tablet is 0.5 to 10% (wt/wt). 24. The oral preparation of claim 22 or 23, wherein the disintegrant is at least one selected from the group consisting of corn starch, crystalline cellulose, low substituted hydroxypropylcellulose, carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, carboxymethyl starch sodium and crospovidone. 25. The oral preparation of claim 1, wherein a similarity factor f2 of each preparation is in the range of 50.ltoreq.f2.ltoreq.100 when a content of lurasidone per tablet changes over a range of 20 to 120 mg. 26. The oral preparation of claim 1, further comprising: a lubricant, wherein a content of the lubricant per tablet is 1.0% (wt/wt) to 1.43% (wt/wt). 27. The oral preparation of claim 26, wherein the lubricant is at least one selected from the group consisting of magnesium stearate, talc, polyethylene glycol, silica and hydrogenated vegetable oil. 28. The oral preparation of claim 1, wherein the oral preparation is a tablet. 29. An oral preparation, comprising: N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-(2R,3R)-2,3-tetramethyle- ne-butyl]-(1'R,2'S,3'R,4'S)-2,3-bicyclo[2,2,1]heptanedicarboxyimide hydrochloride (lurasidone) of formula (1): ##STR00004## a pregelatinized starch; a water-soluble excipient; and a water-soluble polymer binder, wherein the oral preparation contains 20 to 45% (wt/wt) of lurasidone, the oral preparation contains 20 mg to 120 mg of lurasidone, the pregelatinized starch is incorporated in an amount of 10 to 50% (wt/wt) based on the weight of the oral preparation, and the oral preparation exhibits an equivalent dissolution profile across the range of lurasidone per oral preparation. 30. An oral preparation, comprising: N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-(2R,3R)-2,3-tetramethyle- ne-butyl]-(1'R,2'S,3'R,4'S)-2,3-bicyclo[2,2,1]heptanedicarboxyimide hydrochloride (lurasidone); a pregelatinized starch; a water-soluble excipient; and a water-soluble polymer binder, wherein lurasidone is included in the preparation in an amount of from 20 to 40% (wt/wt), the pregelatinized starch is included in the preparation in an amount of from 10 to 40% (wt/wt), the water-soluble excipient is mannitol or lactose, and the water-soluble polymer binder is at least one selected from the group consisting of hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone and polyvinyl alcohol. 31. An oral preparation, comprising: N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-(2R,3R)-2,3-tetramethyle- ne-butyl]-(1'R,2'S,3'R,4'S)-2,3-bicyclo[2,2,1]heptanedicarboxyimide hydrochloride (lurasidone); a pregelatinized starch; a water-soluble excipient; a water-soluble polymer binder; a disintegrant; and a lubricant, wherein the content of lurasidone in the preparation is 20 to 40% (wt/wt), the content of pregelatinized starch in the preparation is 10 to 30% (wt/wt), the water-soluble excipient is mannitol, the water-soluble polymer binder is hydroxypropylmethylcellulose, and the oral preparation is a tablet. 32. A method for preparing the oral preparation of claim 1, comprising: granulating a powder mixture comprising lurasidone, a pregelatinized starch and a water-soluble excipient by applying a solution of a water-soluble polymer binder. 33. A method for preparing the oral preparation of claim 1, comprising: granulating a powder mixture comprising a pregelatinized starch and a water-soluble excipient by applying a solution or dispersion of lurasidone and a water-soluble polymer binder. 34. A method of treating schizophrenia, comprising administering the oral preparation of claim 1, to a patient suffering from schizophrenia.