Transdermal therapeutic system for administering the active substance buprenorphine

Patent metadata

Field	Value
Publication number	US-9308202-B2
Application number	US-51584807-A
Country	US
Kind code	B2
Filing date	Nov 7, 2007
Priority date	Nov 21, 2006
Publication date	Apr 12, 2016
Grant date	Apr 12, 2016

Abstract

The invention relates to a transdermal therapeutic system for administering the active substance buprenorphine. Said system comprises at least one carboxylic acid that determines the solubility of buprenorphine in the matrix layer and that can likewise be absorbed. The transdermal therapeutic system according to the invention is used in the treatment of pain and is characterized by a considerably increased utilization of the active substance.

First claim

The invention claimed is:

1. A transdermal therapeutic system for administering buprenorphine to the skin, comprising:
an active-ingredient-impermeable backing layer;
at least one pressure-sensitive adhesive matrix layer comprising the active ingredient buprenorphine and laevulinic acid;
wherein the matrix layer comprises a polymer selected from polysiloxanes or polyisobutylene;
wherein the buprenorphine is dissolved in the laevulinic acid to form a solution and
wherein the solution is dispersed, in the form of droplets, in the matrix layer.

2. The transdermal therapeutic system according to claim 1 , wherein the polysiloxane is an amine-resistant dimethylpolysiloxane.

3. The transdermal therapeutic system according to claim 1 , wherein the polysiloxane is a mixture of an amine-resistant and a non-amine-resistant dimethylpolysiloxane, in which the non-amine-resistant dimethylpolysiloxane is present at up to 40% by weight.

4. The transdermal therapeutic system according to claim 1 , wherein the laevulinic acid diffuses into the skin inure quickly than does the active ingredient buprenorphine.

5. The transdermal therapeutic system according to claim 1 , wherein the amount of the dispersed solution is up to 40% by weight.

6. The transdermal therapeutic system according to claim 1 , wherein the laevulinic acid is liquid at skin temperature.

7. The transdermal therapeutic system according to claim 1 , wherein buprenorphine and laevulinic acid are present in the same weight ratio.

8. The transdermal therapeutic system according to claim 1 , wherein the matrix layer is in diffusible contact with a layer based on polyacrylates.

9. The transdermal therapeutic system according to claim 8 , wherein the polyacrylate layer is embodied as a self-adhesive skin contact layer.

10. The transdermal therapeutic system according to claim 9 , wherein the polyacrylate adhesive possesses no free carboxyl groups.

11. The transdermal therapeutic system according to claim 1 , wherein active substance utilization under in vivo conditions of at least 30% is achieved.

12. A method of treating pain which comprises:
administering to a patient, in need thereof, a transdermal therapeutic system for administering buprenorphine to the skin, wherein the transdermal therapeutic system comprises:
an active-ingredient-impermeable backing layer;
at least one pressure-sensitive adhesive matrix layer comprising a therapeutically effective amount of the active ingredient buprenorphine and laevulinic acid;
wherein the matrix layer comprises a polymer selected from polysiloxanes or polyisobutylene;
wherein the buprenorphine is dissolved in the laevulinic acid to form a solution; and
wherein the solution is dispersed, in the form of droplets, in the matrix layer.

13. The transdermal therapeutic system according to claim 2 ,
wherein the polysiloxane is a mixture of an amine-resistant and a non-amine-resistant dimethylpolysiloxane, where the non-amine-resistant dimethylpolysiloxane is present in the mixture at up to 40% by weight;
wherein the laevulinic acid diffuses into the skin more quickly than does the active ingredient buprenorphine and where the laevulinic acid is liquid at skin temperature; and
wherein the amount of the dispersed solution in the matrix layer is up to 40% by weight.

14. The transdermal therapeutic system according to claim 1 , wherein active substance utilization under in vivo conditions of at least 40% is achieved.

15. The transdermal therapeutic system according to claim 1 , wherein active substance utilization under in vivo conditions of at least 50% is achieved.

16. The transdermal therapeutic system according to claim 1 , wherein the matrix layer comprises polyisobutylene.

17. The transdermal therapeutic system according to claim 1 , wherein the droplets in the matrix layer consist essentially of the buprenorphine and the laevulinic acid.

18. The transdermal therapeutic system according to claim 1 , wherein the matrix layer comprises polysiloxane.

19. The transdermal therapeutic system according to claim 1 further comprising a protective layer to be detached before use.

20. The method according to claim 12 , wherein the matrix layer comprises polysiloxane.

Assignees

• Hille Thomas
• Horstmann Michael
• Mueller Walter
• Purdue Pharma Lp

Inventors

• Hille Thomas
• Horstmann Michael
• Mueller Walter

Classifications

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/32

  Alcohol-abuse · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P25/36

  Opioid-abuse · CPC title