STABILIZED TRANSDERMAL DRUG DELIVERY SYSTEM

1 . A transdermal drug delivery device comprising:

(a) a backing film;

(b) a first adhesive layer comprising a solid dispersion, said dispersion comprising:

an first adhesive,

a first therapeutic agent in amorphous form, and

a first combination polymeric stabilizing and dispersing agent comprising a hydrogen bond-forming functional group; and

(c) a protective release liner.

2 . The drug delivery device of claim 1 , having a weight ratio of said polymeric stabilizing/dispersing agent to said therapeutic agent in amorphous form of at least 0.5.

3 . The drug delivery device of claim 1 , wherein at least 95% of said therapeutic agent is in amorphous form after storage at room temperature for at least six months.

4 . The drug delivery device of claim 3 , wherein at least 99% of said therapeutic agent is in amorphous form after storage at room temperature for at least six months.

5 . The drug delivery device of claim 4 , wherein at least 99% of said therapeutic agent is in amorphous form after storage at room temperature for at least 18 months.

6 . The drug delivery device of claim 1 , wherein said therapeutic agent has a skin absorption rate which is increased by at least 50% compared to the skin absorption rate of said therapeutic agent in an identical transdermal drug delivery without said polymeric stabilizing/dispersing agent.

7 . The drug delivery device of claim 1 , wherein said therapeutic agent is selected from the group consisting of (i) scopolamine, oxybutynin, naltrexone, testosterone, estradiol, rotigotine, fentanyl, ethinyl estradiol, or norelgestral, (ii) any pharmaceutically acceptable salts of any of (i), or any combination of any of (i), (ii), or (i) and (ii).

8 . The transdermal drug delivery device of claim 1 , further comprising

(d) a second adhesive layer between said first adhesive layer and said protective release liner, said second adhesive layer comprising:

a second adhesive which may be the same as or different from said first adhesive, a second therapeutic agent in amorphous form which may be the same as or different from said first therapeutic agent, and

a second combination polymeric stabilizing and dispersing agent which may be the same as or different from said first combination polymeric stabilizing and dispersing agent, said agent comprising a hydrogen bond-forming functional group.

9 . The drug delivery device of claim 8 , further comprising:

(e) a membrane between said first and second adhesive layers.

10 . The drug delivery device of claim 1 , wherein said first adhesive layer further comprises a member selected from the group consisting of a skin penetration enhancer, a tackifier, a cohesive promoter, and any combination of any of the foregoing.

11 . The drug delivery device of claim 8 , wherein said first, second, or first and second adhesive layers independently further comprise a member selected from the group consisting of a skin penetration enhancer, a tackifier, a cohesive promoter, and any combination of any of the foregoing.

12 . The drug delivery device of claim 1 , wherein said therapeutic agent in amorphous form contains at least one hydrogen bond-forming group.

13 . The drug delivery device of claim 12 , wherein there is one or more hydrogen bonds between said therapeutic agent in amorphous form and said polymeric stabilizing/dispersing agent and wherein said drug delivery device has greater dispersion capability compared to an identical transdermal drug delivery device without said polymeric stabilizing/dispersing agent.

14 . The drug delivery device of claim 1 , having a weight ratio of polymeric stabilizing/dispersing agent to therapeutic agent in amorphous form of 0.5 or greater.

15 . The drug delivery device of claim 1 , having a weight ratio of said polymeric stabilizing agent to said therapeutic agent in amorphous form of 2 or greater, and wherein said therapeutic agent in amorphous form has a glass transition temperature of less than 50° C.

16 . The drug delivery device of claim 15 , having a weight ratio of polymeric stabilizing agent to therapeutic agent in amorphous form between 2 and 10, and wherein said therapeutic agent in amorphous form has a glass transition temperature of less than 40° C.

17 . The drug delivery device of claim 1 , having a weight ratio of said polymeric stabilizing agent to said therapeutic agent in amorphous form of 0.5 or greater, and wherein said therapeutic agent in amorphous form has a glass transition temperature of at least 60° C.

18 . The drug delivery device of claim 17 , having a weight ratio of said polymeric stabilizing agent to said therapeutic agent in amorphous form between 0.5 and 10, and wherein said therapeutic agent in amorphous form has a glass transition temperature of at least 70° C.

19 . The drug delivery device of claim 18 , having a weight ratio of said polymeric stabilizing agent to said therapeutic agent in amorphous form between 0.5 and 2.

20 . The drug delivery device of claim 1 , wherein said a therapeutic agent in amorphous form contains less than 1.0% crystallinity.

21 . The drug delivery device of claim 1 , wherein said adhesive layer comprises from about 0.05 to about 40 weight % of said therapeutic agent.

22 . The drug delivery device of claim 1 , wherein said adhesive layer comprises from about 1 to about 20 weight % of said therapeutic agent in amorphous form.

23 . The drug delivery device of claim 1 , wherein said adhesive is selected from the group consisting of a polysiloxane, polyisobutylene, an acrylic adhesive, or any combination of any of the foregoing.

24 . A method of manufacturing a transdermal drug delivery device, said method comprising:

(a) mixing

(i) a first uniform solution comprising a first therapeutic agent in amorphous form and a first combination polymeric stabilizing and dispersing agent comprising a hydrogen bond-forming functional group with

(ii) a first adhesive or adhesive solution to form a second solution or suspension,

(b) coating a release liner with said second solution or suspension to form a first coated release liner, and

(c) drying said first coated release liner.

25 . The method of claim 24 , further comprising the step of:

(d) laminating the dry coated release liner onto a backing film.

26 . The method of claim 24 , further comprising the step of:

(e) die-cutting one or more unit dosage forms from the laminate.

27 . The method of claim 24 , wherein one or more of said uniform solution, adhesive, adhesive solution, second solution or suspension independently further comprises a member selected from the group consisting of a skin penetration enhancer, a tackifier, a cohesive promoter, or a combination of any of the foregoing.

28 . The method of claim 24 , further comprising

(a′) mixing

(i) a second uniform solution comprising a second therapeutic agent in amorphous form, which may be the same as or different from said first therapeutic agent, and a second combination polymeric stabilizing and dispersing agent, which may be the same as or different from said first combination stabilizing and dispersing agent comprising a hydrogen bond-forming functional group with

(ii) a second adhesive or adhesive solution, which may be the same as or different from said first adhesive or adhesive solution, to form a third solution or suspension,

(b′) coating a second release liner, which may be the same as or different from said first release liner, with said third solution or suspension,

(c′) drying the coated second release liner,

(d) laminating the first dried coated release liner onto a backing film,

(e) removing said first release liner from said first coated release liner to form a first dried coating layer, and

(f) laminating the second dried coated release liner to said first dried coating layer.

29 . The method of claim 28 , wherein one or more of said first uniform solution, first adhesive or adhesive solution, second solution or suspension, second uniform solution, second adhesive or adhesive solution, or third solution or suspension independently further comprises a member selected from the group consisting of a skin penetration enhancer, a tackifier, a cohesive promoter, and any combination of any of the foregoing.

30 . The method of claim 24 , further comprising:

(a′) mixing

(i) a second uniform solution comprising a second therapeutic agent in amorphous form, which may be the same as or different from said first therapeutic agent, and a second combination polymeric stabilizing and dispersing agent, which may be the same as or different from said first combination stabilizing and dispersing agent, comprising a hydrogen bond-forming functional group with

(ii) a second adhesive or adhesive solution, which may be the same as or different from said first adhesive or adhesive solution, to form a third solution or suspension,

(b′) coating a second release liner, which may be the same as or different from said first release liner, with said third solution or suspension,

(c′) drying the coated second release liner,

(d) laminating the first dried coated release liner onto one side of a membrane, woven mesh, or non-woven mesh, and

(e) laminating the second dried coated release liner onto the second side of said membrane, woven mesh, or non-woven mesh.

31 . The method of claim 30 , wherein steps (d) and (e) occur simultaneously.

32 . The method of claim 30 , wherein step (d) occurs before step (e).

33 . The method of claim 30 , wherein one or more of said first uniform solution, first adhesive or adhesive solution, second solution or suspension, second uniform solution, second adhesive or adhesive solution, or third solution or suspension independently further comprises a member selected from the group consisting of a skin penetration enhancer, a tackifier, a cohesive promoter, and any combination of any of the foregoing.