Transdermal electrotransport delivery device including a cathodic reservoir containing a compatible antimicrobial agent

• US 6,181,963 B1
• Filed: 11/02/1999
• Issued: 01/30/2001
• Est. Priority Date: 11/02/1998
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Cormier, Michel J. N., Murdock, Thomas O., Chin, Ivan W.
• Primary Examiner(s): Kennedy, Sharon
• Assistant Examiner(s): Blyveis, Deborah
• Application Number:
  US09/433,615
• Time in Patent Office: 455 Days
• Field of Search: 604/20, 604/21, 604/890.1, 607/115, 607/145, 607/152, 607/153
• US Class Current: 604/20
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

A transdermal electrotransport drug delivery device having an anode, a cathode and a source of electrical power electrically connected to the anode and the cathode. The cathode includes a cathodic electrode and a cathodic reservoir comprised of a housing composed of a polymeric material and an aqueous medium in contact with the housing. The aqueous medium includes i) a drug or an electrolyte salt or a mixture thereof and ii) a cetylpyridinium salt in an amount sufficient to inhibit microbial growth in the aqueous medium. The polymeric material is compatible with the cetylpyridinium salt. A process is also provided wherein when electric current flows from the source of electrical power so that the drug is transdermally delivered to the patient by electrotransport from the anodic reservoir, the cetylpyridinium salt is not transdermally delivered to the patient by electrotransport from the cathodic reservoir. A process for preparing a transdermal electrotransport drug delivery device is also provided.

Claims

1. A transdermal electrotransport drug delivery device comprised of an anode, a cathode and a source of electrical power electrically connected to the anode and the cathode, the cathode including a cathodic electrode and a cathodic reservoir comprised of a housing composed of a polymeric material and an aqueous medium in contact with the housing, said aqueous medium comprised of i) a drug or an electrolyte salt or a mixture thereof and ii) a cetylpyridinium salt in an amount sufficient to inhibit microbial growth in the aqueous medium wherein said polymeric material is compatible with the cetylpyridinium salt.

2. The transdermal electrotransport drug delivery device of claim 1 wherein the aqueous medium has a pH of from about 3 to about 7.5.

3. The transdermal electrotransport drug delivery device of claim 2 wherein the aqueous medium has a pH of from about 3.5 to about 6.5.

4. The transdermal electrotransport drug delivery device of claim 1 wherein the aqueous medium includes a buffer.

5. The transdermal electrotransport drug delivery device of claim 1 wherein the polymeric material is selected from the group consisting of polyethylene terephthalate, polyethylene terephthalate modified with cyclohexane dimethylol, polypropylene and mixtures thereof.

6. The transdermal electrotransport drug delivery device of claim 1 wherein the cathodic reservoir contains an aqueous medium of an electrolyte salt and is substantially drug free.

7. The transdermal electrotransport drug delivery device of claim 6 wherein the anode includes an anodic electrode and an anodic reservoir that contains a drug.

8. The transdermal electrotransport drug delivery device of claim 7 wherein the anodic reservoir contains fentanyl in a form that can be delivered when current flows from the source of electric power.

9. The transdermal electrotransport drug delivery device of claim 1 wherein the cetylpyridinium salt is a halide salt.

10. The transdermal electrotransport drug delivery device of claim 9 wherein the cetylpyridinium halide salt is cetylpyridinium chloride.

11. The transdermal electrotransport drug delivery device of claim 1 wherein the aqueous medium contains at least about 0.005% by weight of the cetylpyridinium salt.

12. The transdermal electrotransport drug delivery device of claim 11 wherein the aqueous medium contains from about 0.005% to about 2% by weight of the cetylpyridinium salt.

13. The transdermal electrotransport drug delivery device of claim 12 wherein the aqueous medium contains from about 0.01% to about 1% by weight of the cetylpyridinium salt.

14. The transdermal electrotransport drug delivery device of claim 1, including an anion exchange membrane between the cathodic electrode and the cathodic reservoir.

15. A process for transdermally delivering a drug to a patient by electrotransport from a drug delivery device comprised of an anode, a cathode and a source of electrical power electrically connected to the anode and the cathode, the anode including an anodic electrode and an anodic reservoir that contains a drug and the cathode including a cathodic electrode and a cathodic reservoir composed of a polymeric material and containing an aqueous medium comprised of i) an electrolyte salt and ii) a cetylpyridinium salt in an amount sufficient to inhibit microbial growth in the aqueous medium, said polymeric material being compatible with the cetylpyridinium salt, said process comprising providing electric current from the source of electrical power so that the drug is transdermally delivered to the patient by electrotransport from the anodic reservoir and so that cetylpyridinium ions are not transdermally delivered to the patient by electrotransport from the cathodic reservoir.

16. The process of claim 15 wherein the drug is fentanyl in a form that can be delivered when current flows from the source of electric power.

17. The process of claim 15 wherein the aqueous medium is a hydrogel comprised of at least about 0.005% by weight of the cetylpyridinium salt.

18. The process of claim 17 wherein the hydrogel comprises from about 0.005% to about 2% by weight of the cetylpyridinium salt.

19. The process of claim 18 wherein the hydrogel comprises from about 0.01% to about 1% by weight of the cetylpyridinium salt.

20. The process of claim 15 wherein the cetylpyridinium salt is cetylpyridinium chloride.

21. The process of claim 15 wherein substantially no drug is delivered from the cathodic reservoir when current flows from the source of electric power.

22. The process of claim 15 wherein the drug comprises fentanyl.

23. A process of preparing a transdermal electrotransport drug delivery device comprising preparing an aqueous medium comprised of i) a drug or an electrolyte salt or a mixture thereof and ii) a cetylpyridinium salt in an amount sufficient to inhibit microbial growth in the aqueous medium;

and placing the aqueous medium in the cathodic reservoir of a device comprised of an anode, a cathode and a source of electrical power electrically connected to the anode and the cathode, the cathode including a cathodic electrode and a cathodic reservoir comprised of a housing composed of a polymeric material whereby the aqueous medium is in contact with the housing of the cathodic reservoir and wherein said polymeric material is selected so that it is compatible with the cetylpyridinium salt.

24. The process of claim 23 wherein the polymeric material is selected from the group consisting of polyethylene terephthalate, polyethylene terephthalate modified with cyclohexane dimethylol, polypropylene and mixtures thereof.

25. The process of claim 23 wherein the aqueous medium is substantially drug free.

26. The process of claim 23 wherein the cetylpyridinium salt is a halide salt.