Gastric acid secretion inhibiting composition

• US 20080031941A1
• Filed: 07/06/2007
• Published: 02/07/2008
• Est. Priority Date: 04/18/2001
• Status: Abandoned Application

• Current Assignee: Orexo AB
• Original Assignee: Orexo AB
• Inventors: Pettersson, Anders
• Application Number:
  US11/822,502
• Publication Number:
  US 20080031941A1
• Time in Patent Office: Days
• US Class Current: 424/463
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• 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 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 31/04 Antibacterial agents

Abstract

An oral pharmaceutical dosage form comprises pharmacologically effective amounts of an acid susceptible proton pump inhibitor or a salt thereof, an H2 receptor antagonist or a salt thereof and a pharmaceutically acceptable carrier. The dosage form is capable of raising gastric pH to above 4 within two hours after administration and to keep it at that level for at least 4 hours. Also disclosed is a method of manufacture of the dosage form, its use in treating dyspepsia and infection by Helicobacter pylori, and a method of treating disorders associated with gastric acid secretion.

Claims

1. An oral pharmaceutical dosage form comprising pharmacologically effective amounts of an acid susceptible proton pump inhibitor or a salt thereof and an H2 receptor antagonist or a salt thereof, and a pharmaceutically acceptable carrier, wherein the acid susceptible proton pump inhibitor or a salt thereof is separated from the H2 receptor antagonist by an enteric coating.

2. The dosage form of claim 1, wherein the acid susceptible proton pump inhibitor is selected from lanzoprazole, omeprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole, their pharmaceutically acceptable salts, enantiomers and salts of enantiomers.

3. The dosage form of claim 1, comprising from 1 mg to 100 mg per single dose of an acid susceptible proton pump inhibitor or a salt thereof.

4. The dosage form of claim 1, wherein the H2 receptor antagonist is selected from cimetidine, ranitidine, nizatidine and famotidine, their pharmaceutically acceptable salts, isomers and salts of isomers.

5. The dosage form of claim 1, comprising from 1 mg to 800 mg of H2 receptor antagonist or salt thereof.

6. The dosage form of claim 1, wherein said pharmacologically effective amounts are amounts capable to raise gastric pH to above 4 within two hours after administration and to keep it above 4 for at least 4 hours.

7. The dosage form of claim 6, wherein said amounts are capable to keep gastric pH above 4 for at least 8 hours.

8. The dosage form of claim 1, wherein said pharmacologically effective amounts are amounts capable to raise gastric pH to above 3 within 2 hours from administration and to keep it above 3 for at least 4 hours.

9. The dosage form of claim 8, wherein said amounts are amounts capable to keep gastric pH above 3 for at least 8 hours.

10. The dosage form of any of claims 1-9, comprising from 100 mg to 1000 mg of antacid agent and/or alginate.

11. The dosage form of claim 10, wherein the antacid agent comprises one or several of aluminum hydroxide, calcium carbonate, magnesium carbonate, basic magnesium carbonate, magnesium hydroxide, magnesium oxide, sodium hydrogen carbonate.

12. The dosage form of any of claims 1-11, wherein said acid susceptible proton pump inhibitor or a salt thereof is protected by an enteric coating layer and, optionally, a layer separating it from the enteric coating.

13. The dosage form of any of claims 1-12, comprising two concentric layers optionally separated by one or more separating layer(s), one layer comprising said acid susceptible proton pump inhibitor or salt thereof, the other layer comprising said H2 receptor antagonist or salt thereof.

14. The dosage form of claim 13, wherein the inner layer comprises the acid susceptible proton pump inhibitor or salt thereof and the outer layer comprises the H2 receptor antagonist or salt thereof.

15. The dosage form of claims 13, wherein the outer layer comprises the acid susceptible proton pump inhibitor or salt thereof and the inner layer comprises the H2 receptor antagonist or salt thereof.

16. The dosage form of claim 15, wherein the inner layer comprises a disintegrant.

17. A capsule according to any of claims 1-12.

18. A divided powder/pellet formulation according to any of claims 1-12.

19. A tablet according to any of claims 1-16.

20. The tablet of claim 19, divisible.

21. The tablet of claim 19, dispersible in water.

22. The tablet of claim 21, comprising a disintegrant.

30. Use of the dosage form of any of claims 1-22 for the manufacture of a medicament for the treatment of a disorder associated with gastric acid secretion.

31. Use of the dosage form of any of claims 1-22 in association with one or more antibiotic agent(s) for the eradication of Helicobacter pylori.

32. A method of treating disorders associated with dyspepsia, comprising the administration of the dosage form of any of claims 1-22 or the concomitant administration of two separate oral dosage forms, one comprising a pharmacologically effective amount of an acid susceptible proton pump inhibitor or salt thereof, the other comprising a pharmacologically effective amount of an H2 receptor antagonist or salt thereof.

33. A method of treating an infection by Helicobacter pylori, comprising the administration of the dosage form of any of claims 1-22 or the concomitant administration of two separate oral dosage forms, one comprising a pharmacologically effective amount of an acid susceptible proton inhibitor or salt thereof, the other comprising a pharmacologically effective amount of an H2 receptor antagonist or salt thereof, in association with the administration of one or more antibiotic agent(s) effective against H. pylori.

34. The method of claim 32 or 33, comprising a dose regimen capable of maintaining gastric pH above 4 for at least 95% of the time period starting at 2 hours from the administration of the first dose and extending until 6 hours from the administration of the last dose.

35. The method of claim 34, wherein said time period is one week or more.

36. The method of claim 34, wherein said time period is two weeks or more.

37. The method of claim 34, wherein said time period is four weeks or more.

38. The method of claim 32 or 33, comprising a dose regimen capable of maintaining gastric pH above 3 for at least 95% of the time period starting at 2 hours from the administration of the first dose and extending until 6 hours from the administration of the last dose, in particular for four weeks or more.

23. A method for the manufacture of an oral tableted dosage form comprising amounts of an acid susceptible proton pump inhibitor or salt thereof and an H2 receptor antagonist or salt thereof pharmacologically effective in treating a condition related to dyspepsia, the method comprising forming a first layer comprising said acid susceptible proton pump inhibitor or salt thereof, an enteric coat surrounding said first layer, and a second layer comprising said H2 receptor antagonist or salt thereof surrounding said first layer and said enteric coat.

28. The method of any of claims 23-27, wherein said acid susceptible proton pump inhibitor is selected from lansoprazole, omeprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole, their pharmaceutically acceptable salts, enantiomers and salts of enantiomers.

29. The method of any of claims 23-27, wherein said H2 receptor antagonist is selected from are cimetidine, ranitidine, nizatidine and famotidine, their pharmaceutically acceptable salts, isomers and salts of isomers.

24. A method for the manufacture of an oral dosage form comprising amounts of an acid susceptible proton pump inhibitor or salt thereof and an H2 receptor antagonist or salt thereof pharmacologically effective in treating a condition related to dyspepsia, the method comprising forming pellets comprising said acid susceptible proton pump inhibitor or salt thereof, covering said pellets with enteric coat, and mixing said pellets covered with said enteric coat with a carrier comprising said H2 receptor antagonist or salt thereof.

25. The method of claim 24, wherein said carrier comprises a disintegrant.

26. The method of claim 24 or 25, comprising forming a tablet of said mixture.

27. The method of claim 24, comprising filling a capsule capable of disintegrating in gastrointestinal fluids to release its contents with said mixture.