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: a 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; wherein

the first therapeutic agent has a glass transition temperature of at least 70° C., and the weight ratio of the polymeric stabilizing and dispersing agent to the first therapeutic agent in amorphous form is between 0.5 and 2; or

the first therapeutic agent has a glass transition temperature of less than 40° C., and the weight ratio of the polymeric stabilizing and dispersing agent to the first therapeutic agent in amorphous form is between 2 and 10;

wherein the first therapeutic agent is scopolamine or naltrexone; and

wherein the first therapeutic agent in amorphous form is 10% to 20% of the solid dispersion by weight of each.

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

3. The drug delivery device of claim 2 , wherein at least 99% 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 18 months.

5. 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 and dispersing agent.

6. 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, wherein

the second therapeutic agent has a glass transition temperature of at least 70° C., and the weight ratio of the second polymeric stabilizing and dispersing agent to the second therapeutic agent is between 0.5 and 2, or

the second therapeutic agent has a glass transition temperature of less than 40° C., and the weight ratio of the second polymeric stabilizing and dispersing agent to the second therapeutic agent is between 2 and 10; and

wherein the second therapeutic agent in amorphous form is 10% to 20% of the second adhesive layer by weight of each.

7. The drug delivery device of claim 6 , further comprising: (e) a membrane between said first and second adhesive layers.

8. 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.

9. The drug delivery device of claim 6 , wherein said first, second, or both 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.

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

11. The drug delivery device of claim 10 , wherein there is one or more hydrogen bonds between said therapeutic agent in amorphous form and said polymeric stabilizing and dispersing agent and wherein said drug delivery device has greater dispersion capability compared to an identical transdermal drug delivery device without said polymeric stabilizing and dispersing agent.

12. The drug delivery device of claim 1 , wherein the first therapeutic agent in amorphous form contains less than 1.0% crystallinity.

13. 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.

14. 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; wherein

the therapeutic agent has a glass transition temperature of at least 70° C., and the weight ratio of the polymeric stabilizing and dispersing agent to the first therapeutic agent in amorphous form is between 0.5 and 2; or the therapeutic agent has a glass transition temperature of less than 40° C., and the weight ratio of the polymeric stabilizing and dispersing agent to the therapeutic agent is between 2 and 10;

wherein the first therapeutic agent is scopolamine or naltrexone, and

wherein the first therapeutic agent in amorphous form is 10% to 20% of the second solution or suspension by dry weight of each.

15. The method of claim 14 , further comprising the step of: (d) laminating the dry coated release liner onto a backing film.

16. The method of claim 14 , further comprising the step of: (e) die-cutting one or more unit dosage forms from the laminate.

17. The method of claim 14 , wherein one or more of said uniform solution, first 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.

18. The method of claim 14 , further comprising (a′) mixing (i) a third 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 fourth solution or suspension, (b′) coating a second release liner, which may be the same as or different from said first release liner, with said fourth 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, wherein

the second therapeutic agent has a glass transition temperature of at least 70° C., and the weight ratio of the second polymeric stabilizing and dispersing agent to the second therapeutic agent is between 0.5 and 2, or

the second therapeutic agent has a glass transition temperature of less than 40° C., and the weight ratio of the second polymeric stabilizing and dispersing agent to the second therapeutic agent is between 2 and 10; and

wherein the second therapeutic agent in amorphous form is 10% to 20% of the fourth solution or suspension by dry weight of each.

19. The method of claim 18 , wherein one or more of said first uniform solution, first adhesive or adhesive solution, second solution or suspension, third uniform solution, second adhesive or adhesive solution, or fourth 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.

20. The method of claim 14 , further comprising: (a′) mixing (i) a third 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 fourth solution or suspension, (b′) coating a second release liner, which may be the same as or different from said first release liner, with said fourth 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, wherein

the second therapeutic agent has a glass transition temperature of at least 70° C., and the weight ratio of the second polymeric stabilizing and dispersing agent to the second therapeutic agent is between 0.5 and 2, or

the second therapeutic agent has a glass transition temperature of less than 40° C., and the weight ratio of the second polymeric stabilizing and dispersing agent to the second therapeutic agent is between 2 and 10; and

wherein the second therapeutic agent in amorphous form is 10% to 20% of the fourth solution or suspension by dry weight of each.

21. The method of claim 20 , wherein steps (d) and (e) occur simultaneously.

22. The method of claim 20 , wherein step (d) occurs before step (e).

23. The method of claim 20 , 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.

24. The drug delivery device of claim 1 , wherein the polymeric stabilizing and dispersing agent is selected from polyvinylpyrrolidone, poly(vinylpyrrolidone-vinylacetate) copolymer, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, ethylcellulose, or a combination thereof.

25. The drug delivery device of claim 6 , wherein the second therapeutic agent in amorphous form are independently selected from the group consisting of scopolamine, oxybutynin, naltrexone, testosterone, estradiol, rotigotine, fentanyl, ethinyl estradiol, norelgestral, and pharmaceutically acceptable salts thereof.