Dissolvable backing layer for use with a transmucosal delivery device

• US 7,276,246 B2
• Filed: 05/07/2004
• Issued: 10/02/2007
• 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:
  US10/841,892
• Publication Number:
  US 20040224007A1
• Time in Patent Office: 1,243 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 water-dissolvable drug delivery device designed so as to reliably maintain a drug or active agent within a defined region against a mucosal surface. The drug delivery device comprises a water-dissolvable backing layer, an adhesive layer adjacent to at least a portion of the backing layer, and an active layer that is circumscribed by the backing layer and adhesive layer. The backing layer may optionally include a water-dissolvable hydrophilic region and a non-hydrophilic region at least partially encapsulated within the hydrophilic region that inhibits migration of water, drugs, or other active agents through the backing layer. The adhesive layer may be water-activated or it may have a peelable cover layer that, when removed, exposes the adhesive material. The active layer may comprise any drug or other active agent, either alone or in combination with (i) an enhancer that increases the ability of the drug or other active agent to diffuse through a mucosal membrane and/or (ii) a matrix material such as an alginate to hold the active layer together.

Claims

1. A transmucosal delivery device for delivering a drug or other active agent through a mucosal membrane while confining the drug or other active agent within a defined area during delivery, the delivery device comprising:

an active layer comprising at least one drug or other active agent and having an outer perimeter;

a water-dissolvable backing layer comprising at least one hydrophilic polymer, said backing layer extending over said active layer and beyond said outer perimeter of said active layer in order for an overlapping portion of the backing layer to circumscribe said active layer; and

an adhesive layer adjacent to said backing layer comprising at least one mucoadhesive adapted to adhere to a mucosal surface, at least a portion of said adhesive layer extending beyond said outer perimeter of said active layer and being adapted to seal said overlapping portion of said backing layer against the mucosal surface;

the backing layer being adapted to protect said adhesive layer from over-moistening when the transmucosal delivery device is placed against the mucosal surface so as to maintain a seal against the mucosal surface and confine the drug or other active agent within a defined area against the mucosal surface.

2. A transmucosal delivery device as defined in claim 1, wherein said active layer comprises at least one component selected from the group consisting of fentanyl, morphine, other opiates, sumatriptan, other triptans, heparin, interferon, protein, and peptide.

3. A transmucosal delivery device as defined in claim 1, wherein said active layer comprises at least one enhancer that increases the rate at which said drug or other active agent penetrates the mucosal surface.

4. A transmucosal delivery device as defined in claim 1, wherein said active layer comprises at least one matrix material.

5. A transmucosal delivery device as defined in claim 4, wherein said matrix material comprises at least one member selected from the group consisting of alginic acid, alginic acid salt, cellulose, cellulose ether, cellulose ether salt, starch, carrageenan, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, polyvinyl pyrrolidone, acacia, polyacrylic acid polymer, polyacrylic acid copolymer, and derivatives thereof.

6. A transmucosal delivery device as defined in claim 1, wherein said hydrophilic polymer comprises at least one hydrogel.

7. A transmucosal delivery device as defined in claim 6, wherein said hydrogel comprises at least one component selected from the group consisting of gelatin, caseine, other protein-based material, pectin, agar, chitosan, carrageenan, starch, modified starch, dextran, methylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, a cross-linked polymer of sodium carboxymethylcellulose, microcrystalline cellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxylpropylmethylcellulose phthalate, other cellulosic ether, cellulose acetate, cellulose acetate phthalate, other cellulose derivative, polyvinyl alcohol, polyvinylpyrrolidone, cross-linked povidone, other vinyl polymer, other vinyl copolymer, guar gum, poloxamer, polyethylene glycol, polyethylene oxide, a polyacrylic acid, a polyether, an alkoxy polymer, sodium alginate, xanthan gum, other natural hydrogel, a hydrogel derived from natural products, and derivatives thereof.

8. A transmucosal delivery device as defined in claim 1, wherein said backing layer further comprises at least one plasticizer.

9. A transmucosal delivery device as defined in claim 8, wherein said plasticizer comprises at least one component selected from the group consisting of glycerol, propylene glycol, polyethylene glycol, polypropylene glycol, sugar alcohol, and corn syrup.

10. A transmucosal delivery device as defined in claim 1, wherein said hydrophilic polymer is adapted to dissolve over time when exposed to moisture.

11. A transmucosal delivery device as defined in claim 1, wherein said backing layer comprises a formulation and thickness wherein the backing layer dissolves when exposed to moisture within a prescribed time period or range of time periods.

12. A transmucosal delivery device as defined in claim 1, wherein said backing layer comprises a formulation and thickness wherein said backing layer dissolves when exposed to moisture within a time period in a range from about 5 minutes to about 2 hours.

13. A transmucosal delivery device as defined in claim 1, wherein said backing layer inhibits migration of water, a drug or other active agent through said backing layer, to or from the active layer, within a prescribed time period.

14. A transmucosal delivery device as defined in claim 1, wherein said backing layer comprises a sheet or film having a thickness in a range of about 0.1 microns to about 5 millimeters.

15. A transmucosal delivery device as defined in claim 1, wherein said adhesive layer comprises at least one component selected from the group consisting of polyacrylic acid polymer, polyethylene oxide, polyacrylic acid copolymer, polyethylene glycol, starch, cellulosic ether, cellulose ether salt, carrageenan, sodium alginate, and derivatives thereof.

16. A transmucosal delivery device as defined in claim 1, wherein said adhesive layer extends from the outer perimeter of said active layer to an outer perimeter of said backing layer.

17. A transmucosal delivery device as defined in claim 1, wherein a portion of said adhesive layer is disposed between said backing layer and said active layer.

18. A transmucosal delivery device as defined in claim 1, wherein the delivery device is a buccal patch.

19. A transmucosal delivery device as defined in claim 1, wherein said water-dissolvable backing layer comprises:

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

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

20. A transmucosal delivery device as defined in claim 19, wherein said hydrophilic region comprises a continuous phase and said non-hydrophilic region comprises a disperse phase.

21. A transmucosal delivery device as defined in claim 19, wherein said hydrophilic region comprises a continuous phase and said non-hydrophilic region comprises a continuous phase.

22. A transmucosal delivery device as defined in claim 19, wherein said non-hydrophilic region comprises at least one component selected from the group consisting of gaseous voids, hydrophobic liquid droplets, hydrophobic solid particles, non-dissolvable solid particles, oils, fats, fatty acids, salts of fatty acids, waxes, organic polymers, silicone, and inorganic filler particles.

23. A transmucosal delivery device as defined in claim 19, wherein said non-hydrophilic region comprises at least one solid component that transforms into a liquid or softened solid when warmed to body temperature.

24. An oral transmucosal delivery device for delivering a drug or other active agent, in contact with a mucosal membrane, through the mucosal membrane while inhibiting migration of water through a backing layer into the layer containing the drug or other active agent, and while inhibiting migration of the drug or other active agent through the backing layer into the oral cavity, the delivery device comprising:

an active layer comprising a drug or other active agent and having an outer perimeter;

a water-dissolvable backing layer comprising gelatin and gaseous voids dispersed therein, the backing layer extending over the active layer and beyond the outer perimeter of the active layer in order for an overlapping portion of the backing layer to circumscribe the active layer; and

an adhesive layer adjacent to the backing layer comprising at least one polyacrylic acid polymer or polyacrylic acid copolymer adapted to adhere to a mucosal surface in an oral cavity, at least a portion of the adhesive layer extending beyond the outer perimeter of the active layer and being adapted to seal the overlapping portion of the backing layer against the mucosal surface;

the backing layer being adapted to protect the adhesive layer from saliva when the transmucosal delivery device is placed against mucosa in an oral cavity so as to maintain a seal against the mucosa;

the backing layer being adapted to inhibit migration of water through the backing layer into the active layer; and

the backing layer being adapted to inhibit migration of the drug or other active agent through the backing layer into the oral cavity.

25. An oral transmucosal delivery device for delivering a drug or other active agent, in contact with a mucosal membrane, through a mucosal membrane while confining the drug or other active agent within a defined area during delivery, the delivery device comprising:

an active layer comprising at least one drug or other active agent and having an outer perimeter;

a water-dissolvable backing layer extending over the active layer and beyond the outer perimeter of the active layer in order for an overlapping portion of the backing layer to circumscribe the active layer, wherein the backing layer comprises;

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

at least one non-hydrophilic region, at least partially or wholly encapsulated within the hydrophilic region, that is adapted to inhibit migration of water, the drug, or other active agent through the backing layer and that is adapted to disperse when no longer encapsulated within the hydrophilic region; and

an adhesive layer adjacent to the backing layer comprising at least one mucoadhesive polymer adapted to adhere to a mucosal surface in an oral cavity, at least a portion of the adhesive layer extending beyond said outer perimeter of the active layer and being adapted to seal the overlapping portion of the backing layer against the mucosal surface,

the backing layer being adapted to protect the adhesive layer from saliva when the transmucosal delivery device is placed against the mucosa in an oral cavity so as to maintain a seal against the mucosa and confine the drug or other active agent within a defined area against the mucosa.