Dissolvable backing layer for use with a transmucosal delivery device

• US 7,306,812 B2
• Filed: 05/07/2004
• Issued: 12/11/2007
• Est. Priority Date: 05/09/2003
• Status: Expired due to Fees

• Current Assignee: Cephalon Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Cephalon Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Zhang, Hao
• Primary Examiner(s): Kennedy, Sharon E.
• Application Number:
  US10/841,893
• Publication Number:
  US 20040224008A1
• Time in Patent Office: 1,313 Days
• Field of Search: 424/426, 424/427, 424/428, 424/430, 424/434, 424/435, 424/436, 424/448, 424/449
• US Class Current: 424/434
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence

Abstract

A dissolvable backing layer for use with transmucosal drug delivery devices includes a dissolvable hydrophilic region and a non-hydrophilic region that inhibits or slows migration of water, drugs, other active agents, or other molecules through the backing layer. The non-hydrophilic region can be a disperse phase of gaseous voids, droplets of a hydrophobic liquid, solid particles of a hydrophobic material, or water insoluble particles that are not necessarily hydrophobic. In the alternative, the non-hydrophilic region may comprise a continuous layer or component that is readily dispersible upon dissolving of the hydrophilic region. The backing layers may be used within any transmucosal delivery device used to delivery drugs or other active agents across a mucosal surface.

Claims

1. A dissolvable backing layer for use with a transmucosal delivery device adapted for placement against mucosa, comprising:

a hydrophilic region comprising at least one hydrophilic polymer that is adapted to dissolve over time when exposed to moisture; and

a non-hydrophilic region at least partially encapsulated within said hydrophilic region and that is adapted to at least partially inhibit migration of water, active agents or other molecules through the backing layer and that is adapted to disperse when no longer encapsulated within said hydrophilic region.

2. The dissolvable backing layer of claim 1, said hydrophilic polymer comprising at least one component selected from the group consisting of gelatin, other proteins, pectin, agar, chitosan, carrageenan, starch, modified starch, cellulose ethers, cellulose esters, other cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone, cross-linked povidone, guar gum, poloxamer, polyethylene glycol, polyethylene oxide, polyacrylic acid, sodium alginate, xanthan gum, and derivatives thereof.

3. The dissolvable backing layer of claim 1, said hydrophilic polymer having a concentration in a range of about 1% to 100% by weight of said hydrophilic region.

4. The dissolvable backing layer of in claim 1, said hydrophilic polymer having a concentration in a range of about 5% to about 90% by weight of said hydrophilic region.

5. The dissolvable backing layer of claim 1, said hydrophilic polymer having a concentration in a range of about 10% to about 80% by weight of said hydrophilic region.

6. The dissolvable backing layer of claim 1, said hydrophilic region further comprising at least one plasticizer.

7. The dissolvable backing layer of claim 6, said plasticizer comprising at least one component selected from the group consisting of glycerin, propylene glycol, polyethylene glycol, polypropylene glycol, sugar alcohols, and corn syrup.

8. The dissolvable backing layer of claim 6, said plasticizer having a concentration in a range of 0% to about 80% by weight of said hydrophilic region.

9. The dissolvable backing layer of claim 6, said plasticizer having a concentration in a range of about 2% to about 60% by weight of said hydrophilic region.

10. The dissolvable backing layer of claim 6, said plasticizer having a concentration in a range of about 5% to about 50% by weight of said hydrophilic region.

11. The dissolvable backing layer of claim 1, said hydrophilic region comprising a continuous phase and said non-hydrophilic region comprising a disperse phase.

12. The dissolvable backing layer of claim 11, said non-hydrophilic region comprising a plurality of gaseous voids dispersed throughout said hydrophilic region.

13. The dissolvable backing layer of claim 11, said non-hydrophilic region comprising a plurality of hydrophobic liquid droplets or hydrophobic solid particles dispersed throughout said hydrophilic region.

14. The dissolvable backing layer of claim 13, said hydrophobic liquid droplets or hydrophobic solid particles comprising at least one component selected from the group consisting of oils, vegetable oils, mineral oils, silicone liquids, waxes, magnesium stearate, fats, fatty acids, salts of fatty acids, waxes, polymers, polymeric beads, and solid silicone particles.

15. The dissolvable backing layer of claim 1, said non-hydrophilic region comprising a plurality of water-insoluble inorganic filler particles dispersed throughout said hydrophilic region.

16. The dissolvable backing layer of claim 15, said water-insoluble inorganic filler particles comprising at least one component selected from the group consisting of talc, sand, silica, alumina, titanium dioxide, other transition metal oxides, silicates, limestone, and ground geologic materials.

17. The dissolvable backing layer of claim 1, said hydrophilic and non-hydrophilic regions each comprising a continuous phase.

18. The dissolvable backing layer of claim 17, said non-hydrophilic region comprising at least one of a hydrophobic liquid, hydrophobic solid, or non-water soluble solid.

19. The dissolvable backing layer of claim 17, said non-hydrophilic region comprising at least one component selected from the group consisting of oils, vegetable oils, mineral oils, waxes, magnesium stearate, fats, fatty acids, salts of fatty acids, waxes, polymeric beads, polymers and silicones.

20. The dissolvable backing layer of claim 17, said non-hydrophilic region comprising at least one initially solid component that transforms into a liquid or softened solid when warmed to body temperature.

21. The dissolvable backing layer of claim 1, said non-hydrophilic region comprising at least two different types of components selected from the group consisting of gaseous voids, hydrophobic liquids, hydrophobic solids, and water-insoluble inorganic filler particles.

22. The dissolvable backing layer of claim 1, said hydrophilic region comprising about 10% to about 95% by volume of the backing layer and said non-hydrophilic region comprising about 5% to about 90% by volume of the backing layer.

23. The dissolvable backing layer of claim 1, said hydrophilic region comprising about 15% to about 90% by volume of the backing layer and said non-hydrophobic region comprising about 10% to about 85% by volume of the backing layer.

24. The dissolvable backing layer of claim 1, said hydrophilic region comprising about 20% to about 85% by volume of the backing layer and said non-hydrophobic region comprising about 15% to about 80% by volume of the backing layer.

25. The dissolvable backing layer of claim 1 the backing layer having a thickness in a range of about 0.1 mm to about 5 mm.

26. The dissolvable backing layer of claim 1, the backing layer having a thickness in a range of about 0.2 mm to about 3.5 mm.

27. The dissolvable backing layer of claim 1, the backing layer having a thickness in a range of about 0.3 mm to about 2 mm.

28. The dissolvable backing layer of claim 1, the backing layer having a formulation and thickness in order for the backing layer to become dissolved within the oral cavity when exposed to saliva within a prescribed time period or range.

29. The dissolvable backing layer of claim 1, the backing layer having a formulation and thickness in order for the backing layer to become dissolved within the oral cavity when exposed to saliva within a time period in a range of about 1 minute to about 2 hours.

30. The dissolvable backing layer of claim 1, the backing layer having a formulation and thickness in order for the backing layer to become dissolved within the oral cavity when exposed to saliva within a time period in a range from about 10 minutes to about 1 hour.

31. The dissolvable backing layer of claim 1, the backing layer decreasing the permeability coefficient of one or more water soluble molecules by at least about 25% compared to a backing layer in the absence of the non-hydrophilic region.

32. The dissolvable backing layer of claim 1, the backing layer decreasing the permeability coefficient of one or more water soluble molecules by at least about 50% compared to a backing layer in the absence of the non-hydrophilic region.

33. The dissolvable backing layer of claim 1, the backing layer decreasing the permeability coefficient of one or more water soluble molecules by at least about 75% compared to a backing layer in the absence of the non-hydrophilic region.

34. A dissolvable backing layer of claim 1 comprising:

a hydrophilic region comprising at least one hydrophilic polymer having a concentration in a range of about 10% to about 80% by weight of said hydrophilic region and at least one plasticizer having a concentration in a range of about 5% to about 50% by weight of said hydrophilic region, said hydrophilic region is adapted to dissolve over time when exposed to moisture; and

a non-hydrophilic region at least partially encapsulated within said hydrophilic region comprising at least one of gaseous voids, a hydrophobic liquid, a hydrophobic solid, or a non-water soluble solid, and that is adapted to at least partially inhibit migration of water, active agents or other molecules through the backing layer and that is adapted to disperse when no longer encapsulated within said hydrophilic region;

said backing layer having a thickness in a range of about 0.1 mm to about 5 mm.

35. A dissolvable backing layer of claim 1 comprising:

a hydrophilic region comprising gelatin and glycerin that is adapted to dissolve over time when exposed to moisture; and

a non-hydrophilic region at least partially encapsulated within said hydrophilic region comprising at least one of gaseous voids, a hydrophobic liquid, a hydrophobic solid, or a non-water soluble solid, and that is adapted to at least partially inhibit migration of water, active agents or other molecules through the backing layer and that is adapted to disperse when no longer encapsulated within said hydrophilic region;

said backing layer having a thickness in a range of about 0.1 mm to about 5 mm.

36. A dissolvable backing layer for use with a transmucosal delivery device adapted for placement against mucosa, comprising:

a hydrophilic region comprising gelatin and glycerin and that is adapted to dissolve over time when exposed to saliva; and

gaseous voids comprising a disperse phase encapsulated within said hydrophilic region in a manner so as to at least partially inhibit migration of water, active agents or other molecules through said backing layer,

said backing layer comprising a sheet or film having a thickness in a range of about 0.1 mm to about 5 mm.

37. The dissolvable backing layer of claim 36, said hydrophilic region comprising about 20% to about 85% by volume of the backing layer and said gaseous voids comprising about 15% to about 80% by volume of the backing layer.

38. The dissolvable backing layer of claim 36, the backing layer comprising a sheet or film having a thickness in a range of about 0.2 mm to about 3.5 mm.

39. The dissolvable backing layer of claim 36, the backing layer comprising a sheet or film having a thickness in a range of about 0.3 mm to about 2 mm.

40. The dissolvable backing layer as defined in claim 36, the backing layer becoming dissolved within the oral cavity when exposed to saliva within a time period and a range of about 1 minute to about 2 hours.

41. The dissolvable backing layer as defined in claim 36, the backing layer becoming dissolved within the oral cavity when exposed to saliva within a time period and a range of about 10 minutes to about 1 hour.

42. A dosage form adapted for transmucosal delivery of an active agent comprising:

an active layer comprising at least one active agent; and

a dissolvable backing layer sized and configured so as to cover a side of said active region, said backing layer comprising;

a hydrophilic region comprising at least one hydrophilic polymer that is adapted to dissolve over time when exposed to moisture; and

a non-hydrophilic region at least partially encapsulated within said hydrophilic region that is adapted to at least partially inhibit migration of said active agent through said backing layer and that is adapted to disperse when no longer encapsulated within said hydrophilic region.

43. The dosage form of claim 42, said active agent comprising at least one drug.

44. The dosage form of claim 42, said active agent comprising sumatriptan.

45. The dosage form of claim 42, said active agent comprising at least one natural or synthetic opiate.

46. The dosage form of claim 42, said active agent comprising at least one of a vitamin or nutrient.

47. The dosage form of claim 42, said active agent comprising at least one member selected from the group consisting of fentanyl, codeine, sufentanil, lofentanil, carfentanil, alfentunil, morphine, other opiates, triptans, interferons, heparin, proteins, peptides, and barbiturates, analgesics, anesthetics, anxolytics, sedatives, anti-depressants, cannobinoids, anticoagulants, antibiotics, antihistamines, blood pressure modulators, and anti-cholesterol drugs.

48. The dosage form of claim 42, said backing layer being sized and positioned relative to the active layer so that the backing layer extends beyond and circumscribes said active layer.

49. The dosage form of claim 42, the dosage form being adapted for use in an oral cavity of a mammal.

50. The dosage form of claim 42, the dosage form comprising at least one other layer in addition to said active layer and said backing layer.

51. The dosage form of claim 50, said other layer being interposed at least partially between said active layer and said backing layer.

52. A method for delivering an active agent across mucosa, comprising:

placing a transmucosal delivery against a mucosal surface, said transmucosal delivery device comprising;

an active layer comprising at least one active agent; and

a dissolvable backing layer sized and configured so as to cover a side of said active region, said backing layer comprising;

a hydrophilic region comprising at least one hydrophilic polymer that is adapted to dissolve over time when exposed to saliva; and

a non-hydrophilic region at least partially encapsulated within said hydrophilic region that is adapted to at least partially inhibit migration of said active agent through said backing layer and that is adapted to disperse when no longer encapsulated within said hydrophilic region; and

allowing said transmucosal delivery device to remain against said mucosal surface so as to provide a desired treatment.

53. The method of claim 52, said transmucosal delivery device being placed into an oral cavity of a mammal.

54. The method of claim 53, said transmucosal delivery device being allowed to remain within the oral cavity until it dissolves.

55. The method of claim 52, said active agent comprising at least one drug.

56. The method of claim 52, said active agent comprising sumatriptan.

57. The method of claim 52, said active agent comprising at least one natural or synthetic opiate.

58. The method of claim 57, said transmucosal delivery device being used to treat breakthrough pain.

59. The method of claim 52, said active agent comprising at least one member selected from the group consisting of fentanyl, codeine, sufentanil, lofentanil, carfentanil, alfentunil, morphine, other opiates, triptans, interferons, heparin, proteins, peptides, and barbiturates, analgesics, anesthetics, anxolytics, sedatives, anti-depressants, cannobinoids, anticoagulants, anti-biotics, antihistamines, blood pressure modulators, and anti-cholesterol drugs.

60. The method of claim 52, said transmucosal delivery device further comprising at least one additional layer interposed at least partially between said active layer and said backing layer.