Passive transdermal device with controlled drug delivery

• US 5,533,995 A
• Filed: 05/13/1994
• Issued: 07/09/1996
• Est. Priority Date: 11/13/1991
• Status: Expired due to Term

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Original Assignee: Elan Corporation PLC (Perrigo Company PLC)
• Inventors: Corish, John, Corrigan, Owen I.
• Primary Examiner(s): Green, Randall L.
• Assistant Examiner(s): Bockelman, Mark
• Application Number:
  US08/244,094
• Time in Patent Office: 788 Days
• Field of Search: 604/20, 604/304, 604/890.1, 604/891.1, 604/892.1, 604/290, 424/449
• US Class Current: 604/890.1
• CPC Class Codes: A61N 1/303 Constructional details electrodes for external use A61N1/0428

Abstract

A transdermal device for the controlled administration of a drug to the skin comprises a reservoir (12) for the drug and an electric circuit which includes an electrode system (13, 14) which is operable to actively transport the drug in a controlled manner from the reservoir (12) towards the skin for transport therethrough, the skin not being part of the electric circuit, and the drug passing through an electrode (13) of said electrode system (13, 14) during the active transport to the skin. The electrode (13) is disposed between the reservoir (12) for the drug and an optional transit chamber (15). The electrode (13) can be permeable to the drug or the electrode can function as a gate, being permeable to the drug in the open condition and less permeable to the drug in the closed condition. The operation of the gate can be determined by the composition or the structure of the electrode (13). The device achieves drug delivery rates comparable to those achieved with iontophoretic devices.

Claims

1. A transdermal device for the controlled administration of a drug to the skin, which comprises a reservoir for the drug, an electric circuit comprising an electrode system of at least two electrodes in which at least one of the electrodes is permeable to the drug, which electrode system has means for electrolytically transporting the drug in a controlled manner within the device by a potential difference applied to the electrodes, the drug passing through the at least one drug permeable electrode of the electrode system, wherein the electrodes are disposed internally of the device such that the skin does not form a part of the electric circuit, means for securing the device in contact with the external skin of a patient, the drug being actively transported from the reservoir in the direction of the skin for transport therethrough, by energising the electrodes.

2. A transdermal device according to claim 1, wherein the drug is one which is not normally capable of being administered passively by the transdermal route.

3. A transdermal device according to claim 1, wherein the at least one drug permeable electrode comprises a porous metallic material.

4. A transdermal device according to claim 3, wherein the at least one drug permeable electrode comprises a metal gauze.

5. A transdermal device according to claim 3, wherein the at least one drug permeable electrode comprises a woven metallic material.

6. A transdermal device according to claim 3, wherein the at least one drug permeable electrode comprises a metal laminate.

7. A transdermal device according to claim 3, wherein the metal is selected from the group consisting of platinum, silver, a coated metal alloy and an uncoated metal alloy.

8. A transdermal device according to claim 1, wherein the at least one drug permeable electrode comprises carbon sheeting.

9. A transdermal device according to claim 1, wherein the at least one drug permeable electrode functions as a gate, being permeable to the drug in the open condition and less permeable to the drug in the closed condition.

10. A transdermal device according to claim 9, wherein the operation of the gate is provided by the at least one drug permeable electrode being constructed of an ion exchange material.

11. A transdermal device according to claim 9, wherein the operation of the gate is provided by the at least one drug permeable electrode formed of a material of variable pore sizes.

12. A transdermal device according to claim 1, wherein the at least one drug permeable electrode electrode which comprises a polymeric material.

13. A transdermal device according to claim 12, wherein the polymeric material is susceptible to ion doping.

14. A transdermal device according to claim 12, wherein the polymeric material has ion exchange properties.

15. A transdermal device according to claim 1, wherein the at least one drug permeable electrode electrode spans the width of the reservoir.

16. A transdermal device according to claim 1, wherein the at least one drug permeable electrode electrode spans the width of the reservoir and wherein the surface of said at least one drug permeable the electrode distal from the reservoir is placed in contact with the skin in use.

17. A transdermal device according to claim 1, further comprising a transit chamber adapted for contact with the skin, wherein the said at least one drug permeable electrode is disposed between the reservoir for the drug and the transit chamber therefor.

33. A transdermal device according to claim 1, wherein the drug is salbutamol.

34. A transdermal device according to claim 1, wherein the drug is nicotine.

35. A transdermal device according to claim 2, wherein a plurality of electrodes permeable to the drug are disposed in the reservoir.

36. A transdermal device according to claim 1, wherein the device includes controlling means operable by a user to selectively transport the drug within and from the reservoir.

37. A transdermal device according to claim 1, further comprising programmable means for controlling the selective transport of the drug within and from the reservoir.

38. A transdermal device according to claim 1, further composing means for achieving a periodic or pulsed delivery of drug.

39. A transdermal device according to claim 1, further comprising housing means, wherein the reservoir and at least one electrode define a unit which is detachably mounted in the housing means.

18. A transdermal device for the controlled administration of a drug to the skin, which comprises a reservoir formed of a shaped mass of a material in which the drug is distributed for storage, a transit chamber adapted for contact with the skin, and an electric circuit comprising an electrode system of at least two electrodes, which electrode system is operable to actively transport the drug electrolytically in a controlled manner within the device, the drug passing through an electrode of the electrode system, which electrode is permeable to the drug and is disposed between the reservoir for the drug and the transit chamber therefor, the electrodes being disposed internally of the device such that the skin does not form part of the electric circuit and such that the drug is electrolytically transported from the reservoir in the direction of the skin for transport therethrough, by energising the electrodes.

19. A transdermal device according to claim 18, wherein the transit chamber is composed of the same material as the reservoir (12).

20. A transdermal device according to claim 18, wherein the transit chamber is composed of a material which is different to that comprising the reservoir.

21. A transdermal device according to claim 18, wherein the material of each of the reservoir and the transit chamber is a gel.

22. A transdermal device according to claim 21, wherein the gel material is formed from a gel forming agent selected from the group consisting of plant extracts, gums, synthetic or natural polysaccharides, polypeptides, alginates, synthetic polymers and mixtures thereof.

23. A transdermal device according to claim 21, wherein the gel forming agent selected from the group consisting of agar and carrageenan.

24. A transdermal device according to claim 18, wherein the transit chamber includes a different drug to that contained in the reservoir.

25. A transdermal device according to claim 18, wherein the drug is one which is not normally capable of being administered passively by the transdermal route.

26. A transdermal device according to claim 18, wherein the drug is salbutamol.

27. A transdermal device according to claim 18, wherein the drug is nicotine.

28. A transdermal device according to claim 18, wherein a plurality of electrodes permeable to the drug are disposed in the reservoir.

29. A transdermal device according to claim 18, wherein the device includes controlling means operable by a user to selectively transport the drug within and from the reservoir.

30. A transdermal device according to claim 18, further comprising programmable means for controlling the selective transport of the drug within and from the reservoir.

31. A transdermal device according to claim 18, further comprising means for achieving a periodic or pulsed delivery of drug.

32. A transdermal device according to claim 18, further comprising housing means, wherein the reservoir, transit chamber and at least one electrode define a unit which is detachably mounted in the housing means.

40. A method for the controlled passive transdermal delivery of at least one drug to a subject, comprising the steps of:

(a) attaching a transdermal device to the skin of the subject, wherein the transdermal device comprises;

i) the at least one drug;

ii) a reservoir for storing the at least one drug; and

iii) an electric circuit comprising an electrode system of at least two electrodes, wherein the electrodes are disposed internally in the device such that the skin does not form part of the electric circuit and wherein the drug is actively transported from the reservoir in the direction of the skin when the electric circuit is energised;

(b) providing a voltage potential across the electric circuit electrodes causing electrolytic transport of the at least one drug in a controlled manner within the device between the electrodes to provide controlled delivery of the at least one drug to the skin of the subject; and

(c) delivering the at least one drug to the subject via controlled passive transdermal delivery.

41. A method for the controlled passive transdermal delivery of at least one drug to a subject, comprising the steps of:

(a) attaching a transdermal device to the skin of the subject, wherein the transdermal device comprises;

i) the at least one drug;

ii) a reservoir for storing the at least one drug;

iii) an electric circuit comprising an electrode system of at least two electrodes in which at least one of the electrodes is permeable to the at least one drug, wherein the electrodes are disposed internally in the device such that the skin does not form part of the electric circuit and wherein the drug is actively transported from the reservoir in the direction of the skin and through the at least one electrode permeable to the at least one drug when the electric circuit is energised;

iv) a transit chamber adapted for contact with the skin, wherein the electrode permeable to the at least one drug is disposed between the reservoir for the drug and the transit chamber;

(b) providing a voltage potential across the electric circuit electrodes causing the electrolytic transport of the at least one drug in a controlled manner within the device between the electrodes and from the reservoir through the electrode permeable to the at least one drug to the transit chamber to allow for the controlled delivery of the at least one drug to the skin of the subject from the transit chamber; and

(c) delivering the at least one drug to the subject via controlled passive transdermal delivery.