Transdermal delivery system

• US 8,246,980 B2
• Filed: 07/28/2003
• 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): FISHER, ABIGAIL L
• Application Number:
  US10/627,990
• Publication Number:
  US 20040081683A1
• Time in Patent Office: 3,312 Days
• Field of Search: 424/443, 424/448, 424/449, 424/484, 514/277
• US Class Current: 424/449
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• 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 an amine-functional drug 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 the amine-functional drug and is impermeable to the protonated form of the amine-functional drug.

Claims

1. A transdermal delivery system (TDS) comprising

a self-adhesive matrix containing a self-adhesive polymer and microreservoirs containing an amine-functional drug in free base form selected from the group consisting of fentanyl and oxybutynin,

wherein the microreservoirs are within the self-adhesive matrix and have a maximum diameter less than the thickness of the self-adhesive matrix;

and

wherein the self-adhesive matrix is permeable to the amine-functional drug in free base form, and the self-adhesive matrix is substantially impermeable to the amine functional drug in protonated form.

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

m.

3. The TDS of claim 1, wherein the self-adhesive matrix is free of silica particles that can absorb salts of the amine functional drug 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.

6. The TDS of claim 5, wherein the silicone pressure sensitive adhesive is 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. The TDS of claim 1, wherein the microreservoirs further 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.

8. The TDS of claim 7, wherein the at least one crystallization inhibitor comprises soluble polyvinylpyrrolidone.

9. The TDS of claim 1, wherein the self-adhesive matrix contains 10³ to 10⁹ microreservoirs per cm² of the surface of the matrix.

10. The TDS of claim 1, wherein the maximum diameter of the microreservoirs is not greater than 35 μ

m.

11. The TDS of claim 1, further comprising a protective foil or sheet to be removed prior to use.

12. The TDS of claim 1, further comprising a backing layer.

13. The TDS of claim 12, wherein the backing layer is inert to the components of the matrix.

14. The TDS of claim 1, wherein the self-adhesive matrix comprises a solid or semisolid semi-permeable polymer.

15. The TDS of claim 1, wherein the self-adhesive matrix contains 10⁶ to 10⁹ microreservoirs per cm² of the surface of the matrix.

16. The TDS of claim 1, further comprising a backing layer being inert to the component of the matrix, and a protective foil or sheet to be removed prior to use,

wherein the matrix contains 10³ to 10⁹ microreservoirs per cm² of the surface of the matrix, and wherein the maximum diameter of the microreservoirs is less than the thickness of the matrix and is not greater than 35 μ

m.

17. A transdermal delivery system (TDS) comprising a self-adhesive matrix containing a self-adhesive polymer and microreservoirs containing an amine-functional drug in free base form selected from the group consisting of aminotetralin compounds,

wherein the microreservoirs are within the self-adhesive matrix and have a maximum diameter less than the thickness of the self-adhesive matrix;

and

wherein the self-adhesive matrix is permeable to the amine-functional drug in free base form, and the self-adhesive matrix is substantially impermeable to the amine functional drug in protonated form.