Extended release oral dosage composition

• US 6,709,676 B2
• Filed: 06/19/2002
• Issued: 03/23/2004
• Est. Priority Date: 12/20/1999
• Status: Expired due to Term

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Schering Corporation (Merck & Co., Inc.)
• Inventors: Cho, Wing-Kee Philip
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Sheikh, Humera N.
• Application Number:
  US10/175,480
• Publication Number:
  US 20030031713A1
• Time in Patent Office: 643 Days
• Field of Search: 424/400, 424/464, 424/465, 424/472
• US Class Current: 424/472
• 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 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• 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: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A bilayer solid composition comprising (a) an immediate release first layer comprising an anti-allergic effective amount of desloratadine and at least one pharmaceutically acceptable excipient and (b) a sustained release second layer comprising an effective amount of a nasal decongestant, e.g. pseudoephedrine sulfate and a pharmaceutically acceptable sustained release agent wherein the composition contains less than about 2% of desloratadine decomposition products is disclosed. A solid composition comprising an anti-allergic effective amount of desloratadine and at least one, and preferably two pharmaceutically acceptable antioxidants is also disclosed.

Claims

1. A bilayer solid composition comprising (1) a first layer comprising an anti-allergic effective amount of desloratadine and a desloratadine-protective amount of a pharmaceutically acceptable water insoluble basic calcium, magnesium or aluminum salt, or of a desloratadine-protective amount of at least one pharmaceutically acceptable antioxidant;

and (2) a second layer comprising an effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, and optionally, a desloratadine-protective amount of at least one pharmaceutically acceptable antioxidant.

2. The bilayer solid composition of claim 1 wherein the first layer is in intimate contact with the second layer.

3. The bilayer solid composition of claim 1 wherein at least about 80% of the desloratadine dissolves in a 0.1N HCl solution at 37°

C. in about 45 minutes.

4. The bilayer solid composition of claim 1 wherein total amount of desloratadinedegradation products is less than or equal to about 2.0% by weight.

5. The bilayer solid composition of claim 1 wherein about 0.1% to about 10% of at least one pharmaceutically acceptable antioxidant is present in the first layer.

6. The bilayer solid composition of claim 1 wherein a desloratadine-protective amount of at least one pharmaceutically acceptable antioxidant is present in the second layer.

7. The bilayer solid composition of claim 1 wherein a pharmaceutically acceptableater insoluble basic calcium, magnesium or aluminum salt antioxidant is present in the first layer.

8. The bilayer solid composition of claim 1 wherein the anti-allergic effective amount of desloratadine in the first layer is about 2.5 mg.

9. The bilayer solid composition of claim 1 wherein the anti-allergic effective amount of desloratadine in the first layer is about 5.0 mg.

10. The bilayer solid composition of claim 1 wherein two pharmaceutically acceptable antioxidants are present in the first layer.

38. A method of treating allergic and inflammatory conditions of the upper and lower airway passages and skin which comprises administering to a patient in need of such treating an effective amount of the bilayer solid composition of claim 1.

39. A method of treating nasal congestion associated with allergic and inflammatory conditions of the upper and lower airway passages and skin which comprises administering to a patient in need of such treating an effective amount of the bilayer solid composition of claim 1.

40. A method of treating urticaria which comprises administering to a patient in need of such treating an effective amount of the bilayer solid composition of claim 1.

41. A method of treating the nasal and non-nasal symptoms of perennial and seasonal allergic rhinitis which comprises administering to a patient in need of such treating an effective amount of the bilayer solid composition of claim 1.

11. A bilayer solid composition comprising (1) a first layer comprising an anti-allergic effective amount of desloratadine and desloratadine-protective amount of a pharmaceutically acceptable water insoluble basic calcium, magnesium or aluminum salt, and (2) a second layer comprising an effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof.

12. The bilayer solid composition of claim 11 wherein the first layer is in intimate contact with the second layer.

13. The bilayer solid composition of claim 11 wherein at least about 80% of the desloratadine dissolves in a 0.1N HCl solution at 37°

C. in about 45 minutes.

14. The bilayer solid composition of claim 11 wherein total amount of desloratadine degradation products is less than or equal to about 2.0% by weight.

15. The bilayer solid composition of claim 11 wherein the anti-allergic effective amount of desloratadine in the first layer is about 2.5 mg.

16. The bilayer solid composition of claim 11 wherein the anti-allergic effective amount of desloratadine in the first layer is about 5.0 mg.

17. A bilayer solid composition comprising (1) a first layer comprising an anti-allergic effective amount of desloratadine and a desloratadine-protective amount of at least one pharmaceutically acceptable antioxidant;

and (2) a second layer comprising an effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable excipient, and a desloratadine-protective amount of at least one pharmaceutically acceptable antioxidant, and wherein total amount of desloratadine degradation products is less than or equal to about 2.0% by weight.

18. The bilayer solid composition of claim 17 wherein the first layer is in intimate contact with the second layer.

19. The bilayer solid composition of claim 17 wherein at least about 80% of the desloratadine dissolves in a 0.1N HCl solution at 37°

C. in about 45 minutes.

20. The bilayer solid composition of claim 17 wherein about 0.1% to about 10% of at least one pharmaceutically acceptable antioxidant is present in the first layer.

21. The bilayer solid composition of claim 17 wherein the anti-allergic effective amount of desloratadine in the first layer is about 2.5 mg.

22. The bilayer solid composition of claim 17 wherein the anti-allergic effective amount of desloratadine in the first layer is about 5.0 mg.

23. The bilayer solid composition of claim 17 wherein two pharmaceutically acceptable antioxidants are present in the first layer.

24. A bilayer solid composition comprising (a) an immediate release first layer comprising an anti-allergic effective amount of desloratadine and at least one pharmaceutically acceptable excipient and (b) a sustained release second layer comprising an effective amount of a pseudoephedrine, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, and wherein total amount of desloratadine degradation products is less than or equal to about 2% by weight, and wherein at least about 80% of the desloratadine dissolves in a 0.1N HCl solution at 37°

C. in about 45 minutes.

25. The bilayer solid composition of claim 24 wherein total amount of desloratadine degradation products is less than or equal to about 1.5% by weight.

26. A bilayer solid composition comprising a first layer and a second layer, wherein the first layer is an immediate release layer comprising:

27. The bilayer solid composition of claim 26 wherein at least about 80% of the desloratadine dissolves in a 0.1N HCl solution at 37°

C. in about 45 minutes.

28. A bilayer solid composition comprising (1) a first layer comprising 2.5 mg of desloratadine and desloratadine-protective amount of a pharmaceutically acceptable water insoluble basic calcium, magnesium or aluminum salt, and (2) a second layer comprising 120 mg of pseudoephedrine or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, and wherein total amount of desloratadine degradation products is less than or equal to about 2% by weight.

29. The bilayer solid composition of claim 28 wherein at least about 80% of the desloratadine dissolves in a 0.1N HCl solution at 37°

C. in about 45 minutes.

30. A bilayer solid composition comprising (1) a first layer comprising 5 mg of desloratadine and desloratadine-protective amount of at least one pharmaceutically acceptable antioxidant, and (2) a second layer comprising 120 mg of pseudoephedrine or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, and wherein total amount of desloratadine degradation products is less than or equal to about 2% by weight.

31. The bilayer solid composition of claim 30 wherein at least about 80% of the desloratadine dissolves in a 0.1N HCl solution at 37°

C. in about 45 minutes.

32. A bilayer solid composition comprising a first layer and a second layer, wherein the first layer is an immediate release layer comprising:

33. The bilayer solid composition of claim 32 wherein at least about 80% of the desloratadine dissolves in a 0.1N HCl solution at 37°

C. in about 45 minutes.

35. The bilayer solid composition of claim 33 wherein at least about 80% of the desloratadine dissolves in a 0.1N HCl solution at 37°

C. in about 45 minutes.

34. A bilayer solid composition comprising a first layer and a second layer, wherein the first layer is an immediate release layer comprising:

36. A bilayer solid composition comprising a first and second layer, wherein the first layer is an immediate release first layer comprises:

37. The bilayer solid composition of claim 36 wherein at least about 80% of the desloratadine dissolves in a 0.1N HCl solution at 37°

C. in about 45 minutes.