Stable capsule preparation

• US 20070141137A1
• Filed: 03/03/2005
• Published: 06/21/2007
• Est. Priority Date: 03/04/2004
• Status: Abandoned Application

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Nonomura, Muneo, Ito, Hiroki, Nagahara, Naoki
• Application Number:
  US10/591,164
• Publication Number:
  US 20070141137A1
• Time in Patent Office: Days
• US Class Current: 424/451
• 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 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 9/4816 Wall or shell material
• CPC Class Codes: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Abstract

A capsule in which an unstable active ingredient has been stabilized is obtained by lowering the moisture content of a solid preparation (granules, subtilis, tablets, etc.) containing a chemical unstable to moisture such as an imidazole PPI compound by drying or the like, and then filling in a capsule comprising a water-soluble polysaccharide such as pullulan as the main component or a PEG-containing gelatin capsule. For the further stabilization, the capsule per se may be dried. The capsule preparation thus obtained is a stable capsule preparation with the use of a capsule being stable at a low moisture content which contains a chemical unstable to moisture such as an imidazole compound.

Claims

1. A capsule preparation, which comprises a medicine unstable to moisture, is stable in a low moisture state and has pH-independent disintegration properties.

2. The capsule preparation according to claim 1, which is stable in a low moisture state which is less or equal to relative humidity of about 35%.

3. The capsule preparation according to claim 1, wherein the main component of the capsule is a gelatin containing polyethylene glycol.

4. The capsule preparation according to claim 1, wherein the main component of the capsule is a water-soluble polysaccharide.

5. The capsule preparation according to claim 1, wherein the main component of the capsule is pullulan.

6. The capsule preparation according to claim 1, which combines a capsule shell comprising gelatin containing polyethylene glycol as the main component and a capsule shell comprising pullulan as the main component.

7. The capsule preparation according to claim 1, wherein the medicine unstable to moisture is a proton pump inhibitor (PPI).

8. The capsule preparation according to claim 7, wherein the PPI is an imidazole type compound represented by the formula (I′

);

wherein the ring C′

is an optionally substituted benzene ring or an optionally substituted aromatic mono-heterocyclic ring, R⁰ is a hydrogen atom, an optionally substituted aralkyl group, an acyl group or an acyloxy group, each of R¹, R² and R³ which may be the same or different, and is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkoxyl group, or an optionally substituted amino group, and Y is a nitrogen atom or CH, or an optically active isomer thereof or a salt thereof.

9. The capsule preparation according to claim 8, wherein C′

is an optionally substituted benzene ring.

10. The capsule preparation according to claim 7, wherein the PPI is lansoprazole, omeprazole, rabeprazole, pantoprazole, tenatoprazole, or an optically active isomer thereof or a salt thereof.

11. The capsule preparation according to claim 7, wherein the PPI is lansoprazole.

12. The capsule preparation according to claim 7, wherein the PPI is an optically active isomer (R-isomer) of lansoprazole.

13. The capsule preparation according to claim 1, wherein the medicine unstable to moisture is a prodrug of PPI.

14. The capsule preparation according to claim 1, wherein the content in the capsule is a powdered medicine.

15. The capsule preparation according to claim 1, wherein the content in the capsule is fine granules optionally coated, granules optionally coated and/or tablets optionally coated.

16. The capsule preparation according to claim 15, which contains at least two solid preparations selected from fine granules, granules and tablets in combination.

17. The capsule preparation according to claim 16, wherein the combined solid preparations have different medicine release properties.

18. The capsule preparation according to claim 16, wherein at least one of the combined solid preparations has a coating layer.

19. The capsule preparation according to claim 18, wherein the coating layer is an enteric coating layer.

20. The capsule preparation according to claim 18, wherein the coating layer contains a controlled-release coating layer.

21. The capsule preparation according to claim 20, wherein the controlled-release coating layer is a pH-dependent soluble controlled-release coating film containing a polymer soluble within a range of pH 6.0 to pH 7.5.

22. The capsule preparation according to claim 21, wherein the controlled-release coating layer is a diffusion-control type controlled-release film.

23. The capsule preparation according to claim 21, wherein the controlled-release coating layer is a time release type controlled-release coating film.

24. The capsule preparation according to claim 16, which contains fine granules, granules or tablets having an enteric coating layer in combination with fine granules, granules or tablets having a controlled-release coating layer.