Transdermal delivery system for the administration of rotigotine

• US 8,246,979 B2
• Filed: 07/22/2003
• Issued: 08/21/2012
• Est. Priority Date: 07/30/2002
• Status: Active Grant

• Current Assignee: UCB Pharma GmbH (UCB SA)
• Original Assignee: UCB Pharma GmbH (UCB SA)
• Inventors: Schacht, Dietrich Wilhelm, Hannay, Mike, Wolff, Hans-Michael
• Primary Examiner(s): Schnizer, Richard
• Assistant Examiner(s): Buckley, Audrea
• Application Number:
  US10/623,864
• Publication Number:
  US 20050079206A1
• Time in Patent Office: 3,318 Days
• Field of Search: 424/449, 424/443, 424/447, 424/448
• US Class Current: 424/449
• CPC Class Codes: A61K 31/38 having sulfur as a ring hetero atom
• CPC Class Codes: A61K 9/7061 Polyacrylates
• 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: A61K 9/7076 the adhesive comprising ingredients of undetermined constitution or reaction products thereof, e.g. rosin or other plant resins

Abstract

An improved transdermal delivery system (TDS) comprises a self-adhesive matrix comprising a solid or semi-solid semi-permeable polymer which contains rotigotine in its free base form as a multitude of microreservoirs within the matrix. The self-adhesive matrix is highly permeable to the free base of rotigotine and is impermeable to the protonated form of rotigotine.

Claims

1. A transdermal delivery system (TDS) comprising a backing layer and a self-adhesive matrix containing rotigotine, wherein the self-adhesive matrix comprises a solid or semi-solid semi-permeable polymer

(1) wherein rotigotine in its free base form is incorporated, and wherein said free base has been isolated prior to its incorporation into the matrix,

(2) which comprises a multitude of microreservoirs within the matrix, said microreservoirs containing rotigotine free base,

(3) which is permeable to the free base of rotigotine,

(4) which is substantially impermeable to the protonated form of rotigotine, and

(5) wherein all the microreservoirs have a maximum diameter that is less than the thickness of the matrix;

and wherein the backing layer is inert to the components of the matrix.

2. The TDS of claim 1, wherein the microreservoirs have a mean diameter in the range of 0.5 to 20 μ

m.

3. The TDS of claim 1, wherein the self-adhesive matrix is free of particles that can absorb salts of rotigotine at the TDS/skin interface.

4. The TDS of claim 1, wherein the self-adhesive matrix comprises a silicone pressure sensitive adhesive.

5. The TDS of claim 1, wherein the self-adhesive matrix comprises two or more silicone pressure sensitive adhesives as the main adhesive components.

6. The TDS of claim 5, wherein the two or more silicone pressure sensitive adhesives comprise a blend of a high tack silicone pressure sensitive adhesive comprising polysiloxane with a resin and a medium tack silicone pressure sensitive adhesive comprising polysiloxane with a resin.

7. A method for treatment of a patient suffering from a disease treatable with rotigotine, comprising applying the TDS of claim 1 to the skin of the patient.

8. The TDS of claim 1, wherein the microreservoirs additionally contain at least one crystallization inhibitor comprising soluble polyvinylpyrrolidone, a copolymer of polyvinylpyrrolidone and vinyl acetate, polyethylene glycol, polypropylene glycol, glycerol, a fatty acid ester of glycerol and/or a copolymer of ethylene and vinyl acetate.

9. The TDS of claim 8, wherein the at least one crystallization inhibitor comprises soluble polyvinylpyrrolidone.

10. The TDS of claim 1, comprising within the matrix 10³ to 10⁹ microreservoirs per cm² of the surface of the matrix.

11. The TDS of claim 1, comprising within the matrix 10⁶ to 10⁹ microreservoirs per cm² of the surface of the matrix.

12. The TDS of claim 1, wherein the microreservoirs have a maximum diameter not greater than 35 μ

m.

13. The TDS of claim 1, wherein the microreservoirs have a maximum diameter of 2.5 to 30 μ

m.

14. The TDS of claim 1, wherein any amount of rotigotine salt present comprises less than 5% w/w of the self-adhesive matrix.

15. The TDS of claim 1, wherein any amount of rotigotine salt present comprises less than 2% w/w of the self-adhesive matrix.

16. The TDS of claim 1, wherein any amount of rotigotine salt present comprises less than 1% of the self-adhesive matrix.

17. The TDS of claim 1, wherein the free base of rotigotine has been isolated in solid form prior to the incorporation in the matrix.

18. The TDS of claim 1, wherein the microreservoirs containing rotigotine free base distributed in the matrix have a mean diameter between 1-40% of the thickness of the matrix.