ORALLY-DISINTERGRATING SOLID PREPARATION

• US 20110091563A1
• Filed: 03/10/2009
• Published: 04/21/2011
• Est. Priority Date: 03/11/2008
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Watanabe, Yasuko, Kurasawa, Takashi, Omachi, Yoshihiro
• Granted Patent: US 9,241,910 B2
• Time in Patent Office: Days
• US Class Current: 424/494
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Abstract

The present invention provides an orally-disintegrating solid preparation such as a tablet produced by tabletting fine granules showing controlled release of a pharmaceutically active ingredient and an additive, and the like, and the orally-disintegrating solid preparation containing fine granules coated with a coating layer containing a polymer affording a casting film having an elongation at break of about 100-about 700%. With the preparation, breakage of fine granules during tabletting can be suppressed in the production of an orally-disintegrating solid preparation containing fine granules showing controlled release of a pharmaceutically active ingredient.

Claims

1. An orally-disintegrating solid preparation comprising fine granules showing controlled release of a pharmaceutically active ingredient, which has a coating layer comprising a polymer affording a casting film having an elongation at break of about 100%-about 700%.

2. The preparation of claim 1, further comprising a plasticizer, wherein the polymer is an enteric polymer.

3. The preparation of claim 1, wherein the fine granules are obtained by coating fine granules comprising the pharmaceutically active ingredient with a coating layer comprising a polymer affording a casting film having an elongation at break of about 100-about 700%.

4. The preparation of claim 3, wherein the fine granules comprising the pharmaceutically active ingredient are enteric fine granules.

5. The preparation of claim 1, wherein the polymer is an enteric polymer.

6. The preparation of claim 3, wherein the polymer is coated in an amount of about 5-about 80 wt % of the fine granules comprising the pharmaceutically active ingredient.

7. The preparation of claim 1, wherein the fine granules has an average particle size of about 500 μ

m or below.

8. The preparation of claim 1, wherein the coating layer is formed on the outermost layer of the fine granules.

9. The preparation of claim 1, further comprising a coating layer comprising a water-soluble sugar alcohol on the outermost layer of the fine granules.

10. The preparation of claim 2, wherein the content of the plasticizer is about 1-about 20 wt % of the weight of the solid content of the polymer.

11. The preparation of claim 2, wherein the plasticizer is triethyl citrate.

12. The preparation of claim 4, wherein the enteric fine granules comprising the pharmaceutically active ingredient are pH-dependent controlled release fine granules.

13. The preparation of claim 12, wherein the pH-dependent controlled release fine granules are obtained by coating core granules comprising the pharmaceutically active ingredient with a controlled release film.

14. The preparation of claim 13, wherein the controlled release film comprises a polymer substance that dissolves at not less than pH 6.0 and not more than pH 7.5.

15. The preparation of claim 13, wherein the core granules further comprise a basic inorganic salt.

16. The preparation of claim 13, wherein the controlled release film is formed via an intermediate coating layer formed on the core granules.

17. The preparation of claim 14, wherein the polymer substance comprises a mixture of one or more kinds selected from the group consisting of hypromellose phthalate, cellulose acetate phthalate, carboxymethyl ethyl cellulose, methyl methacrylate methacrylic acid copolymer, methacrylic acid-ethyl acrylate copolymer, methacrylic acid-methyl acrylate-methyl methacrylate copolymer, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate and shellac.

18. The preparation of claim 16, wherein the controlled release film has a polymer substance content of about 30-about 100 wt % of the fine granules.

19. The preparation of claim 16, wherein the controlled release film has a polymer substance content of about 50-about 100 wt % of the fine granules.

20. The preparation of claim 1, wherein the pharmaceutically active ingredient is unstable to acid.

21. The preparation of claim 20, wherein the pharmaceutically active ingredient unstable to acid is a proton pump inhibitor.

22. The preparation of claim 21, wherein the proton pump inhibitor is lansoprazole or an optically active form thereof or a salt thereof.

35. The preparation of claim 1, wherein the total weight of the preparation is about 1000 mg or below.

36. The preparation of claim 1, wherein the oral disintegration time is about 90 seconds or less.

23. An orally-disintegrating solid preparation comprising (1) fine granules A showing controlled release of a pharmaceutically active ingredient and (2) fine granules B with a different release rate of a pharmaceutically active ingredient from that of the fine granules of (1), which has a coating layer comprising a polymer affording a casting film having an elongation at break of about 100%-about 700%.

24. The preparation of claim 23, wherein the pharmaceutically active ingredient of the fine granules A and that of the fine granules B are the same.

25. The preparation of claim 23, wherein the fine granules B have an average particle size of about 500 μ

m or below.

26. The preparation of claim 23, wherein the fine granules B are enteric fine granules that dissolve at not less than pH 5.0 and not more than pH 6.0.

27. The preparation of claim 23, wherein the fine granules B are coated with a coating layer comprising an enteric polymer that dissolves at not less than pH 5.0 and not more than pH 6.0.

28. The preparation of claim 26, wherein the enteric fine granules comprise one or more kinds of aqueous enteric polymer bases selected from hypromellose phthalate, cellulose acetate phthalate, hydroxypropyl methylcellulose acetate succinate, methacrylic acid-ethyl acrylate copolymer, methacrylic acid-methyl acrylate-methyl methacrylate copolymer, carboxymethyl ethyl cellulose and shellac.

29. The preparation of claim 24, wherein the fine granules B are pH-dependent controlled release fine granules obtained by coating core granules comprising the pharmaceutically active ingredient with a controlled release film comprising a polymer substance that dissolves at not less than pH 6.0 and not more than pH 7.5, wherein the controlled release film is formed via an intermediate coating layer formed on the core granules, and the controlled release film has a polymer substance content of about 10-about 70 wt % of the fine granules.

30. The preparation of claim 24, wherein the fine granules A and the fine granules B comprise the pharmaceutically active ingredient at a weight ratio of 1:

10-10;

1.

31. The preparation of claim 23, further comprising an additive.

32. The preparation of claim 31, wherein the additive comprises a water-soluble sugar alcohol.

33. The preparation of claim 31, wherein the additive comprises a disintegrant.

34. The preparation of claim 31, wherein the fine granules A is comprised at 10-50 wt %, the fine granules B is comprised at 10-30 wt %, and the additive is comprised at 20-80 wt %, each relative to the whole preparation.

37. The preparation of claim 23, which is capable of achieving an average pH in the stomach of not less than 4 at 0.5 hr after oral administration and maintaining said pH or higher pH for 14 hours or longer.

38. The preparation of claim 23, wherein the pharmaceutically active ingredient is R-lansoprazole or a salt thereof, which reaches the maximum blood drug concentration in about 5 hr and maintains the maximum blood drug concentration of not less than 100 ng/mL for about 4 hr or longer, when 30 mg of the pharmaceutically active ingredient is administered orally.

40. The preparation of claim 23, wherein the total weight of the preparation is about 1000 mg or below.

41. The preparation of claim 23, wherein the oral disintegration time is about 90 seconds or less.

39. A method of suppressing breakage of fine granules showing controlled release of a pharmaceutically active ingredient, which are comprised in an orally-disintegrating tablet obtained by tabletting the fine granules and an additive, which method comprises, during production of the tablet, coating the fine granules with a coating layer comprising a polymer affording a casting film having an elongation at break of about 100-about 700%.