Composition material for transmucosal delivery

• US 20060147498A1
• Filed: 01/23/2004
• Published: 07/06/2006
• Est. Priority Date: 01/24/2003
• Status: Active Grant

• Current Assignee: Magle Holding AB
• Original Assignee: Magle Holding AB
• Inventors: Forshell, Gustaf Plym, Lidgard, Hans Henrik, Jonsson, Ingemar
• Granted Patent: US 8,846,075 B2
• Time in Patent Office: Days
• US Class Current: 424/441
• CPC Class Codes: A61K 9/0058 Chewing gums non-medicinal aspects, preparing chewing gum A23G4/00; chewing gum for care of the teeth or oral cavity, e.g. with breath freshener A61Q11/00
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/009 Sachets, pouches characterised by the material or function of the envelope with gastric retention A61K9/0065; sachets which are not administered but function merely as a container are classified according to the content, e.g. sachets comprising powder for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 25/34 Tobacco-abuse

Abstract

The invention refers to a composition material that is intended for rapid transmucosal delivery in the mouth of a biologically active substance when in contact with saliva. The composition material comprises at least one ionic carbohydrate, having at least one biologically active substance ionically bound thereto, and at least one wetable non-soluble polymeric carbohydrate. The invention also refers to a method of preparing the composition material, which comprises the steps of: (a) providing a mixture of the at least one biologically active substance and at least one ionic carbohydrate in a solvent having a permissive pH for ionic bonding of the at least one biologically active substance to the at least one ionic carbohydrate; (b) mixing the mixture in the solvent for a period that is sufficient for allowing the ionic bonding to take place; and (c) recovering the mixture from the solvent.

Claims

1. A composition material, which comprises at least one ionic carbohydrate, having at least one biologically active substance ionically bound thereto, and at least one wetable non-soluble polymeric carbohydrate, for rapid transmucosal delivery in the mouth of said at least one biologically active substance.

2. The composition material as in claim 1, wherein said at least one ionic carbohydrate is an ionic polymeric carbohydrate or an ionic oligomeric carbohydrate.

3. The composition material as in claim 2, wherein said ionic polymeric carbohydrate is an anionic natural polymeric carbohydrate.

4. The composition material as in claim 3, wherein said anionic natural polymeric carbohydrate is alginate pectin, xanthan, or hyaluronic acid.

5. The composition material as in claim 3, wherein said anionic natural polymeric carbohydrate is an anionically derivatized natural polymeric carbohydrate.

6. The composition material as in claim 5, wherein said anionically derivatized natural polymeric carbohydrate is a sulfopropyl or carboxymethyl derivatized natural polymeric carbohydrate.

7. The composition material as in claim 5, wherein said anionically derivatized natural polymeric carbohydrate is a cellulose or a starch derivative.

8. The composition material as in claim 2, wherein said ionic polymeric carbohydrate is a cationic natural polymeric carbohydrate.

9. The composition material as in claim 8, wherein said cationic natural polymeric carbohydrate is chitosan.

10. The composition material as in claim 8, wherein said cationic natural polymeric carbohydrate is a cationically derivatized natural polymeric carbohydrate.

13. The composition material as in claim 2, wherein said ionic polymeric or said ionic oligomeric carbohydrate is cross-linked.

14. The composition material as in claim 2, wherein said ionic oligomeric carbohydrate is a synthetic carbohydrate.

15. The composition material as in claim 1, wherein said at least one wetable non-soluble polymeric carbohydrate is a natural carbohydrate.

16. The composition material as in claim 15, wherein said natural carbohydrate is cellulose or hemicellulose.

17. The composition material as in claim 16, which comprises a mixture of pectin, cellulose, and hemicellulose.

18. The composition material as in claim 1, wherein said at least one wetable non-soluble polymeric carbohydrate can adsorb, absorb, or non-specifically bind said at least one biologically active substance.

19. The composition material as claim 1, which has a water content of less than 15%.

20. The composition material as in claim 1, which further comprises a pH controlling agent.

21. The composition material as in claim 20, wherein said pH controlling agent is an ionic carbohydrate.

22. The composition material as in claim 21, wherein said ionic carbohydrate has a charge opposite that of said at least one ionic carbohydrate.

23. The composition material as in claim 20, wherein said pH controlling agent is ammonia or a carbonate or phosphate buffer.

24. The composition material as in claim 1, which in contact with said saliva has a pH that is similar or higher than the pK_a of said at least one biologically active substance.

25. The composition material as in claim 1, wherein said at least one biologically active substance is a protein, a peptide, an alkaloid, a drug for the treatment of migraine, a hypnotic, a sedative, a local anaesthetic, an analgesic, or a drug for the treatment of a psychiatric disorder.

26. The composition material as in claim 25, wherein said peptide is desmopressin, lypressin, oxytocin, nafarelin, buserelin, or a growth hormone.

27. The composition material as in claim 25, wherein said alkaloid is nicotine, cotinine, or lobeline, or a derivative or a salt thereof, or caffeine.

28. The composition material as in claim 25, wherein said drug for the treatment of migraine is an ergot alkaloid or a 5HT₁-receptor agonist.

29. The composition material as in claim 25, wherein said local anaesthetic is lidocaine or mepivacaine.

30. The composition material as in claim 23, wherein said nicotine content is between 0.05 and 6 mg per dose.

31. The composition material as in claim 1 in the form of a sheet, discrete pieces, granules, tablets, pills, capsules, lozenges or chewing gum.

32. The composition material as in claim 31, wherein said composition material is in the form of a sheet and said sheet has a thickness of less than 5 mm.

33. The composition material as in claim 31, wherein said composition material is in the form of pieces and said pieces are in the form of a fine mesh gauze.

34. A pouch containing the composition material as claimed in claims 1, which is made of a flexible liquid permeable material.

35. The pouch as in claim 34, wherein said flexible liquid permeable material is a fabric.

36. The pouch as in claim 34, wherein said fabric is made of polycarbonate.

37. The pouch as in claim 34, which contains between 0.05 and 1.0 g of said composition material.

38. An envelope for the composition material as claimed in claim 1, which is made of a barrier material.

39. The envelope as in claim 38, wherein said barrier material is an aluminium foil.

40. The envelope as in claim 38, wherein said barrier material is coated with Barex®

g.

11. The composition material as in 10, wherein said cationically derivatized natural polymeric carbohydrate is a diethylaminoethyl or diethyl (2-hydroxypropyl)amminoethyl derivatized natural polymeric carbohydrate.

12. The composition material as in 10, wherein said cationically derivatized natural polymeric carbohydrate is a cationic derivative of cellulose or starch.

41. A method of preparing a composition material for rapid transmucosal delivery of at least one biologically active substance, when in contact with a body liquid, which comprises the steps of:

(a) providing a mixture of said at least one biologically active substance and at least one ionic carbohydrate in a solvent having a permissive pH for ionic bonding of said at least one biologically active substance to said at least one ionic carbohydrate;

(b) mixing said mixture in said solvent for a period that is sufficient for allowing said ionic bonding to take place; and

(c) recovering said mixture from said solvent.

42. The method as in claim 41, wherein said at least one ionic carbohydrate is an ionic polymeric carbohydrate or an ionic oligomeric carbohydrate.

43. The method as in claim 42, wherein said ionic polymeric carbohydrate is an anionic natural polymeric carbohydrate.

44. The method as in claim 43, wherein said anionic natural polymeric carbohydrate is alginate pectin, xanthan, or hyaluronic acid.

45. The method as in claim 43, wherein said anionic natural polymeric carbohydrate is an anionically derivatized natural polymeric carbohydrate.

46. The method as in claim 42, wherein said ionic polymeric carbohydrate is a cationic natural polymeric carbohydrate.

47. The method as in claim 46, wherein said cationic natural polymeric carbohydrate is chitosan.

48. The method as in claim 46, wherein said cationic natural polymeric carbohydrate is a cationically derivatized natural polymeric carbohydrate.

49. The method as in claim 41, wherein said biologically active substance is a protein, a peptide, an alkaloid, a drug for the treatment of migraine, a hypnotic, a sedative, a local anaesthetic, an analgesic, or a drug for the treatment of a psychiatric disorder.

50. The method as in claim 41, wherein said solvent is a volatile hydrophilic solvent.

51. The method as in claim 50, wherein said solvent is ethanol, water, or a mixture thereof.

52. The method as in claim 41, which further comprises the step (a′

) of adding a pH controlling agent to said mixture in order to obtain said permissive pH.

53. The method as in claim 52, wherein said pH controlling agent is a volatile acid.

54. The method as in claim 53, wherein said volatile acid is acetic acid or formic acid.

55. The method as in claim 52, wherein said pH controlling agent is a ammonia.

56. The method as in claim 41, which further comprises the step (a″

) of adding at least one wetable non-soluble natural polymeric carbohydrate to said mixture.

57. The method as in claim 56, wherein said at least one wetable non-soluble polymeric carbohydrate is a natural carbohydrate.

58. The method as in claim 56, wherein said at least one wetable non-soluble natural polymeric carbohydrate is cellulose or hemicellulose.

59. The method as in claim 41, wherein said mixture is recovered by evaporation to dryness.

60. The method as in claim 41, which further comprises the step (c′

) of adding a pH controlling agent to said recovered mixture.

61. The method as in claim 60, wherein said pH controlling agent is ammonia or a carbonate or phosphate buffer.