Polyvinylpyrrolidone For The Stabilization Of A Solid Dispersion Of The Non-Crystalline Form Of Rotigotine

• US 20190314294A1
• Filed: 05/23/2019
• Published: 10/17/2019
• Est. Priority Date: 12/22/2009
• Status: Abandoned Application

• Current Assignee: LTS Lohmann Therapie-Systeme AG, UCB Pharma GmbH (UCB SA)
• Original Assignee: UCB Pharma GmbH (UCB SA)
• Inventors: WOLFF, Hans-Michael, ARTH, Christoph, QUERE, Luc, MULLER, Walter
• Application Number:
  US16/420,501
• Publication Number:
  US 20190314294A1
• Time in Patent Office: 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 nom-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, wherein the weight ratio of rotigotine to polyvinylpyrrolidone is in a range from about 9:

3.5 to about 9;

6.

2. The method of claim 1, wherein the weight ratio of rotigotine to polyvinylpyrrolidone is in a range from about 9:

3.5 to about 9;

4.5.

3-13. -13. (canceled)

14. 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 and polyvinylpyrrolidone (PVP), wherein the weight ratio of rotigotine to PVP is in a range from about 9:

3.5 to about 9;

6.

15. The method of claim 14, wherein the weight ratio of rotigotine to (PVP) is in a range from about 9:

3.5 to about 9;

4.5.

16. The method of claim 14, wherein the rotigotine is rotigotine free base.

17. The method of claim 16, further comprising mixing rotigotine free base and the PVP in a solution to obtain the dispersed phase.

18. The method of claim 14, wherein the PVP has a molecular weight of 1,000,000 to 1,500,000 g/mol.

19. The method of claim 14, wherein the dispersing agent comprises at least one silicone pressure sensitive adhesive.

20. The method of claim 19, wherein the dispersing agent comprises a mixture of at least two silicone pressure sensitive adhesives.

21. The method of claim 20, wherein the mixture of at least two silicone pressure sensitive adhesives comprises BIO-PSA®

Q7 4301 and BIO-PSA®

Q7 4201.

22. The method of claim 14, wherein the dispersing agent comprises at least a first adhesive having a complex viscosity between 40 and 250 MP.

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

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

25. The method of claim 14, 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.

26. The method of claim 14, 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.

27. The method of claim 14, 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.