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

• US 10,350,174 B2
• Filed: 05/17/2018
• Issued: 07/16/2019
• Est. Priority Date: 12/22/2009
• Status: Active Grant

• 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
• Primary Examiner(s): Ramachandran, Umamaheswari
• Application Number:
  US15/982,744
• Publication Number:
  US 20180263921A1
• Time in Patent Office: 425 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 stable solid dispersion comprising a silicone dispersing agent which is a two-part mixture of solution-based silicones and a dispersed phase, said dispersed phase comprising rotigotine free base and polyvinylpyrrolidone, wherein a weight ratio of rotigotine free base to polyvinylpyrrolidone is about 9:

4 to about 9;

6.

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

3. The solid dispersion of claim 1, wherein the solid dispersion has a complex viscosity between 5 and 15 MP.

4. The solid dispersion of claim 1, wherein rotigotine free base and polyvinylpyrrolidone are in a multitude of microreservoirs.

5. A pharmaceutical composition comprising a solid dispersion according to claim 1.

6. A transdermal therapeutic system comprising a solid dispersion of claim 1.

7. The transdermal therapeutic system of claim 6, comprising 0.1 to about 3.15 mg/cm′

of rotigotine free base and wherein the weight ratio of rotigotine free base to polyvinylpyrrolidone is 9;

6.

8. The solid dispersion of claim 1, wherein the dispersing agent comprises at least a first adhesive having a complex viscosity between 40 and 250 MP.

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

10. The solid dispersion of claim 9, wherein the dispersing agent has a complex viscosity between 5 and 25 MP.

11. The solid dispersion of claim 1, 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.

12. The solid dispersion of claim 1, 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.

13. The solid dispersion of claim 1, 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.

14. The solid dispersion of claim 1, wherein said dispersed phase is obtained by mixing rotigotine free base polymorphic form II and the polyvinylpyrrolidone in a solution.

15. The solid dispersion of claim 1, wherein the PVP has a molecular weight of 1,000,000 to 1,500,000 g/mol.

16. The solid dispersion of claim 1, wherein the two-part mixture of solution-based silicones is BIO-PSA®

Q7 4301 and BIO-PSA®

Q7 4201.