Device for the transdermal delivery of diclofenac

• US 6,193,996 B1
• Filed: 03/25/1999
• Issued: 02/27/2001
• Est. Priority Date: 04/02/1998
• Status: Expired due to Fees

• Current Assignee: 3M Innovative Properties Company (3M Company)
• Original Assignee: 3M Innovative Properties Company (3M Company)
• Inventors: Coors, Carsten, Effing, Jochem J., Becker, Anja N.
• Primary Examiner(s): Harrison, Robert H.
• Application Number:
  US09/276,630
• Time in Patent Office: 705 Days
• Field of Search: 424/449, 424/448, 514/567, 514/825, 604/304, 604/890.1
• US Class Current: 424/449
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/7061 Polyacrylates
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents

Abstract

The present invention provides a pressure sensitive skin adhesive comprising:

(a) a copolymer of one or more alkyl(meth)acrylates containing 4 to 12 carbon atoms in the alkyl group and one or more hydrophilic monomers;

(b) a mixture of penetration enhancers comprising:

(i) an alkyl ester of an aliphatic monocarboxylic acid containing 1 to 5 carbon atoms in the alkyl group

(ii) an alkyl pyrrolidone and

(iii) an alkane polyol

(c) a therapeutically effective amount of diclofenac or a pharmaceutically acceptable salt thereof.

Further provided is a transdermal drug delivery device containing the pressure sensitive skin adhesive.

Claims

1. A pressure sensitive skin adhesive comprising:

(a) a copolymer of one or more alkyl(meth)acrylates containing 4 to 12 carbon atoms in the alkyl group and one or more hydrophilic monomers;

(b) a mixture of penetration enhancers comprising;

(i) an alkyl ester of an aliphatic monocarboxylic acid containing 1 to 5 carbon atoms in the alkyl group;

(ii) an N-alkyl-2-pyrrolidone or a compound of the formula (I)

 

wherein R₁ is H or alkyl and R₂ is the residue of an aliphatic hydrocarbon and

(iii) an alkane polyol; and

(c) a therapeutically effective amount of diclofenac or a pharmaceutically acceptable salt thereof.

2. A pressure sensitive skin adhesive according to claim 1 wherein the weight ratio of monomer units derived from said alkyl(meth)acrylates to monomer units derived from said hydrophilic monomers in said copolymer is between 98:

2 and 80;

20.

3. A pressure sensitive skin adhesive according to claim 1 wherein said hydrophilic monomer is selected from the group consisting of carboxylic acid containing monomers, N-vinyl-2-pyrrolidone, vinylimidazoles, vinyl acetates, (meth)acrylamides, N-vinyl valerolactam, N-vinyl caprolactam, hydroxy containing monomers, mono-(meth)acrylates of poly(oxyalkylene), tetra-alkylammonium containing monomers and amino group containing monomers.

4. A pressure sensitive skin adhesive according to claim 1 wherein said hydrophilic monomer is selected from the group consisting of acrylic and methacrylic acid.

5. A pressure sensitive skin adhesive according to claim 1 wherein said alkane polyol is selected from the group consisting of propylene glycol and ethylene glycol.

6. A pressure sensitive skin adhesive according to claim 1 wherein said N-alkyl-2-pyrrolidone has 6 to 14 carbon atoms in the alkyl group.

7. A pressure sensitive skin adhesive according to claim 6 wherein said N-alkyl-2-pyrrolidone is N-octyl 2-pyrrolidone.

8. A pressure sensitive skin adhesive according to claim 1 wherein said alkyl ester of an aliphatic monocarboxylic acid is isopropyl myristate.

9. A pressure sensitive skin adhesive according to claim 1 wherein the total amount of said mixture of penetration enhancers is between 10 and 40% by weight of the total weight of said pressure sensitive skin adhesive.

10. A pressure sensitive skin adhesive according to claim 9 wherein said mixture of penetration enhancers comprises between 30 and 70% by weight of said alkyl ester of an aliphatic monocarboxylic acid;

between 3 and 25% by weight of said N-alkyl-2-pyrrolidone or compound of the formula (I)

wherein R₁ is H or alkyl and R₂ is the residue of an aliphatic hydrocarbon; and

between 20 and 45% by weight of said alkane polyol.

11. A pressure sensitive skin adhesive according to claim 1 wherein the diclofenac or pharmaceutically acceptable salt thereof is diclofenac sodium.

12. A pressure sensitive skin adhesive according to claim 1 wherein the diclofenac or pharmaceutically acceptable salt thereof is present in an amount of about 3 to 8 percent by weight based on the total weight of said pressure sensitive skin adhesive.

13. A transdermal drug delivery device comprising on a backing an adhesive layer comprising the pressure sensitive skin adhesive according to claim 1.

14. A method of treating inflammation or relieving pain in a subject comprising placing a pressure sensitive skin adhesive according to claim 1 in contact with the skin of the subject and allowing the pressure sensitive skin adhesive to remain in contact with the skin for a time effective to establish or maintain a therapeutically effective blood level of diclofenac or a pharmaceutically acceptable salt thereof in the subject.