Pharmaceutical composition

• US 9,907,794 B2
• Filed: 06/08/2015
• Issued: 03/06/2018
• Est. Priority Date: 05/26/2005
• Status: Active Grant

• Current Assignee: Sumitomo Pharmaceuticals Company Limited (Sumitomo Chemical Company Limited)
• Original Assignee: Sumitomo Dainippon Pharma Company Limited (Sumitomo Chemical Company Limited)
• Inventors: Fujihara, Kazuyuki
• Primary Examiner(s): Pihonak, Sarah
• Application Number:
  US14/733,204
• Publication Number:
  US 20150265611A1
• Time in Patent Office: 1,002 Days
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

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-tetramethylene-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.

Claims

1. A tablet for oral administration, comprising:

from 20 mg to 120 mg of N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-(2R,3R)-2,3-tetramethylene-butyl]-(1′

R,2′

S,3′

R,4′

S)-2,3-bicyclo[2,2,1]heptane-dicarboxyimide hydrochloride (lurasidone) as an active ingredient;

a pregelatinized starch;

a water-soluble excipient;

a water-soluble polymer binder; and

a lubricant,

wherein the tablet includes lurasidone at a content ratio of 20 to 45% (wt/wt);

wherein the tablet has a dissolution rate of 80% or more at 30 minutes as measured according to Japanese Pharmacopoeia, Dissolution test, Method 2, where the tablet is subjected to the Dissolution test using paddle rotation at a rotation rate of 50 rpm in 900 mL of a diluted McIlvaine buffer having a pH of 3.8 to 4.0;

wherein the tablet has a similar dissolution profile to a second tablet comprising from 20 mg to 120 mg of lurasidone,

wherein similarity of the dissolution profiles is exhibited by the tablet and a second tablet having a similarity factor 12 value of 50 or more,

wherein the tablet and the second tablet are prepared according to the same method, and comprise the same ratio of lurasidone, pregelatinized starch, water-soluble excipient, water-soluble polymer binder, and lubricant, and

the second tablet has a different lurasidone content than the tablet.

2. The tablet of claim 1, comprising 20 mg to 40 mg of lurasidone, wherein the second tablet comprises more than 40 mg up to 120 mg of lurasidone.

3. The tablet of claim 1, wherein both the tablet and the second tablet comprise more than 40 mg up to 120 mg of lurasidone.

4. The tablet of claim 1, comprising more than 40 mg up to 120 mg of lurasidone, wherein the second tablet comprises 20 mg to 40 mg of lurasidone.

5. The tablet of claim 1, wherein both the tablet and the second tablet comprise 20 mg to 40 mg of lurasidone.

6. The tablet of claim 1, further comprising a disintegrant.

7. The tablet of claim 6, wherein the disintegrant comprises at least one of corn starch, crystalline cellulose, low substituted hydroxypropylcellulose, carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, carboxymethyl starch sodium, and crospovidone.

8. The tablet of claim 1, wherein the water-soluble excipient comprises at least one of mannitol and lactose.

9. The tablet of claim 1, wherein the water-soluble polymer binder comprises at least one of hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinylpyrrolidine, and hydroxypropylcellulose.

10. The tablet of claim 1, wherein the lubricant comprises at least one of magnesium stearate, talc, polyethylene glycol, silica, and hydrogenated vegetable oil.

11. The tablet of claim 1, wherein the water-soluble excipient is mannitol, the water-soluble polymer binder is hydroxypropyl methylcellulose, and the lubricant is magnesium stearate.

12. The tablet of claim 6, wherein the disintegrant is croscarmellose sodium, the water-soluble excipient is mannitol, the water-soluble polymer binder is hydroxypropyl methylcellulose, and the lubricant is magnesium stearate.

13. The tablet of claim 1, wherein the pregelatinized starch has a gelatinization ratio of 50% or more.

14. The tablet of claim 1, wherein the dissolution rate is 88% or more.

15. A tablet for oral administration, comprising:

granules comprising;

from 20 mg to 120 mg of N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-(2R,3R)-2,3-tetramethylene-butyl]-(1′

R,2′

S,3′

R,4′

S)-2,3-bicyclo[2,2,1]heptane-dicarboxyimide hydrochloride (lurasidone) as an active ingredient;

a pregelatinized starch;

a water-soluble excipient; and

a water-soluble polymer binder, and

a lubricant blended with the granules,

wherein the tablet includes lurasidone at a content ratio of 20 to 45% (wt/wt);

wherein the tablet has a dissolution rate of 80% or more at 30 minutes as measured according to Japanese Pharmacopoeia, Dissolution test, Method 2, where the tablet is subjected to the dissolution test using paddle rotation at a rotation rate of 50 rpm in 900 mL of a diluted McIlvaine buffer having a pH of 3.8 to 4.0;

wherein the tablet has a similar dissolution profile to a second tablet comprising from 20 mg to 120 mg of lurasidone,

wherein similarity of the dissolution profiles is exhibited by the tablet and a second tablet having a similarity factor f2 value of 50 or more,

wherein the tablet and the second tablet are prepared according to the same method, and comprise the same ratio of lurasidone, pregelatinized starch, water-soluble excipient, water-soluble polymer binder, and lubricant, and

the second tablet has a different lurasidone content than the tablet.

16. The tablet of claim 15, comprising 20 mg to 40 mg of lurasidone, wherein the second tablet comprises more than 40 mg up to 120 mg of lurasidone.

17. The tablet of claim 15, wherein both the tablet and the second tablet comprise more than 40 mg up to 120 mg of lurasidone.

18. The tablet of claim 15, comprising more than 40 mg up to 120 mg of lurasidone, C wherein the second tablet comprises 20 mg to 40 mg of lurasidone.

19. The tablet of claim 15, wherein both the tablet and the second tablet comprise 20 mg to 40 mg of lurasidone.

20. The tablet of claim 15, wherein the granules comprise a disintegrant.

21. The tablet of claim 20, wherein the disintegrant comprises at least one of corn starch, crystalline cellulose, low substituted hydroxypropylcellulose, carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, carboxymethyl stanch sodium, and crospovidone.

22. The tablet of claim 15, wherein the water-soluble excipient comprises at least one of mannitol and lactose.

23. The tablet of claim 15, wherein the water-soluble polymer binder comprises at least one of hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinylpyrrolidine, and hydroxypropylcellulose.

24. The tablet of claim 15, wherein the lubricant comprises at least one of magnesium stearate, talc, polyethylene glycol, silica, and hydrogenated vegetable oil.

25. The tablet of claim 15, wherein the water-soluble excipient is mannitol, the water-soluble polymer binder is hydroxypropyl methylcellulose, and the lubricant is magnesium stearate.

26. The tablet of claim 20, wherein the disintegrant is croscarmellose sodium, the water-soluble excipient is mannitol, the water-soluble polymer binder is hydroxypropyl methylcellulose, and the lubricant is magnesium stearate.

27. The tablet of claim 15, wherein the tablet comprises an uncoated tablet that consists essentially of said granules and lubricant.

28. The tablet of claim 15, wherein the tablet is coated with a film.

29. The tablet of claim 15, wherein the pregelatinized starch has a gelatinization ratio of 50% or more.

30. The tablet of claim 15, wherein the dissolution rate is 88% or more.