Transdermal Delivery System

1 . A transdermal delivery system comprising:

a backing layer;

an adhesive matrix comprising buprenorphine or a salt thereof, a pressure sensitive adhesive including a silicone-type adhesive blended with an acrylate-type adhesive, a solubilizer, a permeation enhancer, and a crystallization inhibitor; and

a release liner.

2 . The transdermal delivery system of claim 1 , wherein the silicone-type adhesive is selected from pressure sensitive adhesives comprising: silicone polymer and resin, and the acrylate-type adhesive is an acrylate-vinylacetate polymer.

3 . The transdermal delivery system of claim 1 , wherein the solubilizer comprises a carboxylic acid and/or the permeation enhancer comprises a fatty acid ester.

4 . The transdermal delivery system of claim 3 , wherein the solubilizer is a C 3 to C 24 carboxylic acid or a C 3 to C 24 keto acid, or is selected from the group consisting of: levulinic acid, lauric acid, lactic acid, oleic acid, linoleic acid, and mixtures thereof.

5 . (canceled)

6 . (canceled)

7 . The transdermal delivery system of claim 63 , wherein the fatty acid ester is a glycerol ester of a C 6 to C 18 fatty acids; or a monoglyceride, diglyceride, triglyceride, or combinations thereof; or is selected from the group consisting of: oleyl oleate, glyceryl monooleate, lauryl lactate, and mixtures thereof.

8 . (canceled)

9 . (canceled)

10 . The transdermal delivery system of claim 1 , wherein the crystallization inhibitor is selected from one or more of the group consisting of: cross-linked polyvinylpyrrolidone, polyvinylpyrrolidone (PVP), or hydroxypropyl methylcellulose (HPMC), and other cellulosic based inhibitors.

11 . The transdermal delivery system of claim 1 , wherein the backing layer is impermeable to the buprenorphine and/or the backing layer comprises one or more of: films of: polyethylene, polyethylene terephthalate (PET), polypropylene, polyurethane, ethylene vinyl acetate (EVA), or polyamide; a metal foil; paper; paper coated with a polymeric material; a PVC foam; a woven fabric; and a non-woven fabric.

12 . (canceled)

13 . The transdermal delivery system of claim 1 , wherein the silicone-type adhesive and the acrylate-type adhesive are present in a ratio range of about 1 to about 1.8 of silicone-type adhesive to acrylate type adhesive.

14 . The transdermal delivery system of claim 1 , wherein the release liner comprises one or more of: paper; coated paper; a plastic film; polyolefins comprising high density polyethylene (HDPE), low density polyethylene (LDPE), or polypropylene (PP) plastic resin; and fluoropolymer-coated films and/or the adhesive matrix further comprises a solvent selected from the group consisting of: ethanol, ethyl acetate, isopropyl alcohol, heptanes, and mixtures thereof.

15 . (canceled)

16 . The transdermal delivery system of claim 1 , wherein the adhesive matrix comprises:

3 to 15% w/w buprenorphine,

20 to 60% w/w silicone adhesive,

20 to 60% w/w polyacrylate adhesive,

3 to 15% w/w cross-linked polyvinylpyrrolidone,

3 to 15% w/w carboxylic acid, and

3 to 15% w/w fatty acid; and

a release liner.

17 . (canceled)

18 . The transdermal delivery system of 16 , wherein the adhesive matrix forms a single layer on the backing layer, and wherein there is no peripheral layer.

19 . A method of relieving pain comprising: applying to skin of a patient in need thereof the transdermal delivery system of claim 1 .

20 . (canceled)

21 . A method of preparing a transdermal delivery system, the method comprising:

dispersing a crystallization inhibitor in a first solvent to form a first solution;

adding a second solvent to the first solution to form a second solution;

adding a solubilizer and a permeation enhancer to the second solution to form a first mixture;

adding a pressure sensitive adhesive including a silicone-type adhesive blended with an acrylate-type adhesive to the first mixture to form a second mixture;

adding buprenorphine base or a salt thereof to the second mixture to form an adhesive matrix mixture; and

coating the adhesive matrix mixture on a backing layer.

22 . The method of claim 21 , wherein

the crystallization inhibitor is selected from one or more of the group consisting of: cross-linked polyvinylpyrrolidone, polyvinylpyrrolidone (PVP), or hydroxypropyl methylcellulose (HPMC), and other cellulosic based inhibitors, and/or

the first solvent and the second solvent are selected from the group consisting of: ethanol, ethyl acetate isopropyl alcohol, heptanes, and mixtures thereof; and/or

the solubilizer comprises a carboxylic acid; and/or

the permeation enhancer comprises a fatty acid ester, and/or

the backing layer comprises one or more of: films of: polyethylene, polyethylene terephthalate (PET), polypropylene, polyurethane, ethylene vinyl acetate (EVA), polyamide; a metal foil; paper; paper coated with a polymeric material; a PVC foam, a woven fabric, or a non-woven fabric.

23 . (canceled)

24 . (canceled)

25 . The method of claim 21 , wherein the solubilizer is a C 3 to C 24 carboxylic acid or a C 3 to C 24 keto acid; or is selected from the group consisting of: levulinic acid, lauric acid, lactic acid, oleic acid, and mixtures thereof.

26 . (canceled)

27 . (canceled)

28 . The method of claim 21 , wherein the permeation enhancer is a glycerol ester of a C 6 to C 18 fatty acid; or is a monoglyceride, diglyceride, triglyceride, or combinations thereof; or is selected from the group consisting of: oleyl oleate, glyceryl monooleate, lauryl lactate, and mixtures thereof.

29 . (canceled)

30 . (canceled)

31 . (canceled)

32 . The method of claim 21 , wherein the silicone-type adhesive and the acrylate-type adhesive are present in a ratio range of about 1 to about 1.8 of silicone-type adhesive to acrylate type adhesive.

33 . The method of claim 21 , wherein the silicone-type adhesive is selected from the pressure sensitive adhesives comprising: silicone polymer and resin, and the acrylate-type adhesive is an acrylate-vinylacetate polymer.

34 . An adhesive matrix comprising:

buprenorphine or a salt thereof;

a pressure sensitive adhesive including a silicone-type adhesive blended with an acrylate-type adhesive;

a solubilizer;

a permeation enhancer;

and a crystallization inhibitor.

35 . The adhesive matrix of claim 34 , wherein the adhesive matrix is formulated into a single layer on a backing layer and wherein there is no peripheral layer.