Bioadhesive pharmaceutical delivery system

• US 5,554,380 A
• Filed: 05/15/1995
• Issued: 09/10/1996
• Est. Priority Date: 08/04/1994
• Status: Expired due to Term

• Current Assignee: Lumara Health IP Ltd. (Apollo Global Management, Inc.)
• Original Assignee: KV Pharmaceutical Company (Apollo Global Management, Inc.)
• Inventors: Riley, Thomas C. Jr., Kirschner, Mitchell I., Cuca, Robert C., Levinson, R. Saul, Lienhop, Keith S.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/441,297
• Time in Patent Office: 484 Days
• Field of Search: 514/772.2, 424/439, 424/440, 424/441, 424/464, 424/465
• 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

Abstract

A solid or semi-solid bioadherent, orally ingestible drug delivery system containing a water-in-oil system having at least two phases, one phase comprises from about 25% to about 75% by volume of an internal hydrophilic phase and the other phase comprises from about 25% to about 75% by volume of an external hydrophobic phase and wherein the external hydrophobic phase is comprised of three components, a) an emulsifier, b) a glyceride ester and c) a wax material.

Claims

1. A solid or semi-solid bioadherent, orally ingestible system, which comprises:

a water-in-oil system having at least two phases, one phase comprises from about 25% to about 75% by volume of an internal hydrophilic phase wherein the hydrophilic phase is selected from the group consisting of water, glycerine, sorbitol solutions, sugar syrups, polymer solutions and mixtures thereof, and the other phase comprises from about 25% to about 75% by volume of an external hydrophobic phase, wherein the external hydrophobic phase is comprised of three components, a) one component being about 5% to about 50% of an emulsifier, b) a second component being about 10% to about 75% of a mixture of glyceride esters of long chain fatty acids and c) a third component being about 10% to about 50% of a wax material.

2. The ingestible system of claim 1, wherein the hydrophilic phase contains an active pharmaceutical material.

3. The ingestible system of claim 2, wherein the active pharmaceutical material is water-soluble.

4. The ingestible system of claim 1, wherein the internal phase is present in amounts of about 50% to about 70% by volume.

5. The ingestible system of claim 1, wherein the external phase contains an active pharmaceutical material.

6. The ingestible system of claim 5, wherein the active pharmaceutical material is water-insoluble.

7. The ingestible system of claim 1, wherein the glyceride esters are selected from the group consisting of mono-, di-, and tri-glyceride esters of long chain fatty acids having from 12 to 32 carbon atoms.

8. The ingestible system of claim 1, wherein the emulsifier present in the hydrophobic phase is selected from the group consisting of sorbitan esters, lecithin, 1 to 5 mole ethoxylates of fatty acids or alcohols, saccharides derivatives and mixtures thereof.

9. The ingestible system of claim 1, wherein the emulsifier is selected from the group consisting of soy lecithin, sorbitan monooleate and mixtures thereof.

10. The ingestible system of claim 1, wherein the external phase is present in amounts of about 25% to about 40% by volume of the entire system.

11. The ingestible system of claim 1, wherein the wax material is selected from the group consisting of animal waxes, vegetable waxes, synthetic waxes and mixtures thereof.

12. A method for treating an oral or esophageal disorder or absorption of an active material for its systemic effect, which comprises:

administering orally a therapeutically effective amount of a solid or semi-solid bioadherent, orally ingestible system, which comprises;

a water-in-oil system having at least two phases, one phase comprises from about 25% to about 75% by volume of an internal hydrophilic phase wherein the hydrophilic phase is selected from the group consisting of water, glycerine, sorbitol solutions, sugar syrups, polymer solutions and mixtures thereof, and the other phase comprises from about 25% to about 75% by volume of an external hydrophobic phase, and wherein the external hydrophobic phase comprises three components, a) one component being about 5% to about 50% of an emulsifier, b) a second component being about 0% to about 75% of a mixture of glyceride esters of long chain fatty acids and c) a third component being about 10% to about 50% of a wax material.

13. The method of claim 12, wherein the hydrophilic phase contains an active pharmaceutical material.

14. The method of claim 13, wherein the active pharmaceutical material is water-insoluble.

15. The method of claim 12, wherein the hydrophilic phase is selected from the group consisting of water, glycerine, sorbitol solutions, sugar syrups, polymer solutions and mixtures thereof.

16. The method of claim 12, wherein the internal phase is present in amounts of about 50% to about 70% by volume.

17. The method of claim 12, wherein the glyceride esters are selected from the group consisting of mono-, di-, and tri-glyceride esters of long chain fatty acids having from 12 to 32 carbon atoms.

18. The method of claim 12, wherein the emulsifier present in the hydrophobic phase is selected from the group consisting of sorbitan esters, lecithin, 1 to 5 mole ethoxylates of fatty acids or alcohols, saccharides derivatives and mixtures thereof.

19. The method of claim 18, wherein the emulsifier is selected from the group consisting of soy lecithin, sorbitan monooleate and mixtures thereof.

20. The method of claim 12, wherein the ingestible system adheres to the oral mucosa and esophageal mucosa for 30 minutes to 24 hours.

21. The method of claim 12, wherein the ingestibte system adheres to the oral mucosa and esophageal mucosa for 2 to 8 hours.

22. A medicated chewing gum composition, which comprises:

a) a gum base in an amount sufficient to form a chewing gum composition;

b) effective amounts of chewing gum additives to soften the gum base; and

c) an effective amount of an active pharmaceutical composition dispersed within a water-in-oil emulsion system having at least two phases, one phase comprises from about 25% to about 75% by volume of an internal hydrophilic phase wherein the hydrophilic phase is selected from the group consisting of water, glycerine, sorbitol solutions, sugar syrups, polymer solutions and mixtures thereof, and the other phase comprises from about 25% to about 75% by volume of an external hydrophobic phase, wherein the external hydrophobic phase is comprised of three components, a) one component being about 5% to about 50% of an emulsifier, b) a second component being about 10% to about 75% of a mixture of glyceride esters of long chain fatty acids and c) a third component being about 10% to about 50% of a wax material.

23. The chewing gum composition of claim 22 wherein the hydrophilic phase contains an active pharmaceutical material.

24. The chewing gum composition of claim 22, wherein the active pharmaceutical material is water-soluble.

25. The chewing gum composition of claim 22, wherein the internal phase is present in amounts of about 50% to about 70% by volume.

26. The chewing gum composition of claim 22, wherein the external phase contains an active pharmaceutical material.

27. The chewing gum composition of claim 22, wherein the active pharmaceutical material is water-insoluble.

28. The chewing gum composition of claim 22, wherein the external phase is present in amounts of about 25% to about 40% by volume of the entire system.

29. The chewing gum composition of claim 22, wherein the internal phase of the emulsion is present in amounts of about 50% to about 70% by volume.

30. The chewing gum composition of claim 22, wherein the active pharmaceutical composition dispersed within the emulsion is coating on the surface of the chewing gum composition.

31. The chewing gum composition of claim 22, wherein the active pharmaceutical composition dispersed within the emulsion is center-filled within the chewing gum composition.

32. The chewing gum composition of claim 22, wherein the active pharmaceutical composition dispersed within the emulsion is homogeneously mixed throughout the chewing gum composition.

33. A medicated confectionery composition, which comprises:

a) a confectionery composition; and

b) an effective amount of an active pharmaceutical composition dispersed within a water-in-oil emulsion system having at least two phases, one phase comprises from about 25% to about 75% by volume of an internal hydrophilic phase wherein the hydrophilic phase is selected from the group consisting of water, glycerine, sorbitol solutions, sugar syrups, polymer solutions and mixtures thereof, and the other phase comprises from about 25% to about 75% by volume of an external hydrophobic phase, wherein the external hydrophobic phase is comprised of three components, a) one component being about 5% to about 50% of an emulsifier, b) a second component being about 10% to about 75% of a mixture of glyceride esters of long chain fatty acids and c) a third component being about 10% to about 50% of a wax material.

34. The confectionery composition of claim 33, wherein the hydrophilic phase contains an active pharmaceutical material.

35. The confectionery composition of claim 34, wherein the active pharmaceutical material is water-soluble.

36. The confectionery composition of claim 33, wherein the internal phase is present in amounts of about 50% to about 70% by volume.

37. The confectionery composition of claim 33, wherein the external phase contains an active pharmaceutical material.

38. The confectionery composition of claim 37, wherein the active pharmaceutical material is water-soluble.

39. The confectionery composition of claim 33, wherein the external phase is present in amounts of about 25% to about 40% by volume of the entire system.

40. The confectionery composition of claim 33 wherein the internal phase of the emulsion is present in amounts of about 50% to about 70% by volume.

41. The confectionery composition of claim 33, wherein the active pharmaceutical composition dispersed within the emulsion is coating on the surface of the confectionery composition.

42. The confectionery composition of claim 33, wherein the active pharmaceutical composition dispersed within the emulsion is center-filled within the confectionery composition.

43. The confectionery composition of claim 33, wherein the active pharmaceutical composition dispersed within the emulsion is homogeneously mixed throughout the confectionery composition.