Polyvinylpyrrolidone for the stabilization of a solid dispersion of the non-crystalline form of rotigotine

• US 10,130,589 B2
• Filed: 01/31/2018
• Issued: 11/20/2018
• Est. Priority Date: 12/22/2009
• Status: Active Grant

• Current Assignee: LTS Lohmann Therapie-Systeme AG, UCB Pharma GmbH (UCB SA)
• Original Assignee: LTS Lohmann Therapie-Systeme AG, UCB Pharma GmbH (UCB SA)
• Inventors: Wolff, Hans-Michael, Arth, Christoph, Quere, Luc, Muller, Walter
• Primary Examiner(s): Chong, Yong S.
• Application Number:
  US15/884,587
• Publication Number:
  US 20180147154A1
• Time in Patent Office: 293 Days
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to a method for stabilizing rotigotine, the method comprising providing a solid dispersion comprising polyvinylpyrrolidone and a non-crystalline form of rotigotine, wherein the weight ratio of rotigotine to polyvinylpyrrolidone is in a range from about 9:3.5 to about 9:6. The present invention also relates to a solid dispersion comprising a dispersing agent and a dispersed phase, said dispersed phase comprising rotigotine and polyvinylpyrrolidone, wherein the weight ratio of rotigotine to polyvinylpyrrolidone is in a range from about 9:3.5 to about 9:6, a pharmaceutical composition comprising such a solid dispersion, in particular a transdermal therapeutic system, as well as a method for the preparation thereof.

Claims

1. A method for stabilizing rotigotine, the method comprising providing a solid dispersion comprising polyvinylpyrrolidone and a non-crystalline form of rotigotine free base, wherein the weight ratio of rotigotine free base to polyvinylpyrrolidone is in a range from about 9:

4 to about 9;

6.

12. The method of claim 1, wherein the solid dispersion further comprises a dispersing agent.

13. The method of claim 12, wherein the dispersing agent comprises at least a first adhesive having a complex viscosity between 40 and 250 MP.

14. The method of claim 13, wherein the dispersing agent comprises at least a second adhesive having a complex viscosity between 1 and 10 MP.

15. The method of claim 14, wherein the dispersing agent has a complex viscosity between 5 and 25 MP.

16. The method of claim 12, wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a complex viscosity between 5 and 15 MP.

17. The method of claim 12, wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a peel adhesion between 3 and 16 N/50 mm at a thickness of 50 g/m² and/or a peel adhesion between 14 and 26 N/50 mm at a thickness of 150 g/m².

18. The method of claim 12, wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a static shear adhesion between 20 and 150 min.

2. A solid dispersion comprising a dispersing agent and a dispersed phase, said dispersed phase comprising rotigotine free base and polyvinylpyrrolidone, wherein the weight ratio of rotigotine free base to polyvinylpyrrolidone is in a range from about 9:

4 to about 9;

6.

3. The solid dispersion of claim 2, wherein the solubility of rotigotine free base in the dispersing agent is below 1 wt-%.

4. The solid dispersion of claim 2, wherein the dispersing agent comprises at least one silicone pressure sensitive adhesive.

5. The solid dispersion of claim 2, wherein the dispersing agent comprises a mixture of a first silicone pressure sensitive adhesive and a second silicone pressure sensitive adhesive and wherein the solid dispersion has a complex viscosity between 5 and 15 MP.

6. The solid dispersion of claim 2, wherein rotigotine free base and polyvinylpyrrolidone are in a multitude of microreservoirs.

7. A pharmaceutical composition comprising a solid dispersion according to claim 2.

10. A transdermal therapeutic system comprising a solid dispersion of claim 2.

19. The solid dispersion of claim 2, wherein the dispersing agent comprises at least a first adhesive having a complex viscosity between 40 and 250 MP.

20. The solid dispersion of claim 2, wherein the dispersing agent comprises at least a second adhesive having a complex viscosity between 1 and 10 MP.

21. The solid dispersion of claim 20, wherein the dispersing agent has a complex viscosity between 5 and 25 MP.

22. The solid dispersion of claim 2, wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a complex viscosity between 5 and 15 MP.

23. The solid dispersion of claim 2, wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a peel adhesion between 3 and 16 N/50 mm at a thickness of 50 g/m² and/or a peel adhesion between 14 and 26 N/50 mm at a thickness of 150 g/m².

24. The solid dispersion of claim 2, wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a static shear adhesion between 20 and 150 min.

8. A transdermal therapeutic system comprising at least one amine-compatible silicone pressure sensitive adhesive, about 0.1 to about 3.15 mg/cm′

of rotigotine free base, and polyvinylpyrrolidone, wherein the weight ratio of rotigotine free base to polyvinylpyrrolidone is in a range from about 9;

4 to about 9;

6.

9. The transdermal therapeutic system of claim 8, wherein rotigotine free base and polyvinylpyrrolidone are contained in a multitude of microreservoirs.

11. A method for preparing a transdermal therapeutic system, the method comprising preparing a solid dispersion comprising a dispersing agent and a dispersed phase, said dispersed phase comprising rotigotine free base and polyvinylpyrrolidone, wherein the weight ratio of rotigotine free base to polyvinylpyrrolidone is in a range from about 9:

4 to about 9;

6.