Control membrane for electrotransport drug delivery

• US 5,169,383 A
• Filed: 09/07/1990
• Issued: 12/08/1992
• Est. Priority Date: 10/03/1988
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Gyory, J. Richard, Theeuwes, Felix, Haak, Ronald P.
• Primary Examiner(s): Pellegrino, Stephen C.
• Assistant Examiner(s): Rafa, Michael
• Application Number:
  US07/571,577
• Time in Patent Office: 823 Days
• Field of Search: 128/798, 128/802, 128/803, 604/20
• US Class Current: 604/20
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0444 Membrane

Abstract

A membrane capable of controlling the rate at which an agent is released from an iontophoretic delivery device is provided. The membrane inhibits agent release from the delivery device when no electrical current is flowing and yet provides minimal impedance to electrically-assisted agent delivery. The membrane is useful both as a control membrane in an iontophoretic agent delivery device and as a test membrane for testing the performance characteristics of an iontophoretic agent delivery device in vitro.

Claims

1. An iontophoretic agent delivery electrode for placement on a body surface and for delivering an agent through the body surface, comprising:

a reservoir containing the agent to be delivered;

conductive means for electrically connecting the reservoir to a source of electrical power;

a means for maintaining the reservoir in agent transmitting relationship to said body surface; and

a membrane interposed between the agent reservoir and the body surface, the membrane permitting electrically-assisted flux (J_EK) of the agent therethrough and substantially preventing passive flux (J_p) of the agent therethrough, the membrane exhibiting a (J_EK +J_p)/J_p ratio of at least about 4, a voltage drop across the membrane of less than about 1 volt, and a J_p of less than about 100 μ

g/hr-cm².

2. The electrode of claim 1, wherein the body surface is selected from the group consisting of skin and mucosal membranes.

3. The electrode of claim 1, wherein the agent comprises a drug.

4. The electrode of claim 1, wherein the agent is selected from the group consisting of peptides, polypeptides and proteins.

5. The electrode of claim 1, wherein the membranes 11/33 to 12/12 is comprised of a material selected from the group consisting of polycarbonates, polyesters, polyamides, styrene-acrylic acid copolymers, polyurethanes, cellulose ester and polyalkylenes.

6. The electrode of claim 1, wherein the membrane comprises a mixture of a hydrophilic resin and a hydrophobic polymer.

7. The electrode of claim 6, wherein the mixture comprises about 10 to 30 vol % hydrophilic resin.

8. The electrode of claim 6, wherein said hydrophilic resin comprises polyvinylpyrrolidone.

9. The electrode of claim 6, wherein said hydrophilic resin comprises an ion exchange resin.

10. The electrode of claim 6, wherein said hydrophobic polymer comprises an ethylene vinyl acetate copolymer having a vinyl acetate content in the range of about 1 to 40 weight percent.

23. The membrane of claim 1, wherein the membrane is comprised of a material selected from the group consisting of polycarbonates, polyesters, polyamides, styrene-acrylic acid copolymers, polyurethanes, cellulose esters and polyalkylenes.

11. An iontophoretic agent delivery device for placement on a body surface comprising:

a donor electrode including a reservoir containing the agent to be delivered, a counter electrode and a source of electrical power electrically connected to the donor and counter electrodes, the donor and counter electrodes adapted to be placed in spaced apart relationship on the body surface;

means for maintaining the agent reservoir in agent transmitting relation with the body surface and for maintaining the counter electrode in electrolyte transmitting relation with the body surface; and

a membrane interposed between the agent reservoir and the body surface, the membrane permitting electrically-assisted flux (J_EK) of the agent therethrough and substantially preventing passive flux (J_p) of the agent therethrough, the membrane exhibiting a (J_EK +J_p)/J_p ratio of at least about 4, a voltage drop across the membrane of less than about 1 volt, and a J_p of less than about 100 μ

g/hr-cm².

12. The device of claim 11, wherein the body surface is selected from the group consisting of skin and mucosal membranes.

13. The device of claim 11, wherein the agent comprises a drug.

14. The device of claim 11, wherein the agent is selected from the group consisting of peptides, polypeptides and proteins.

15. The device of claim 11, wherein the membrane is comprised of a material selected from the group consisting of polycarbonates, polyesters, polyamides, styrene-acrylic acid copolymers, polyurethanes, cellulose esters and polyalkylenes.

16. The device of claim 11, wherein the membrane comprises a mixture of a hydrophilic resin and a hydrophobic polymer.

17. The device of claim 16, wherein the mixture comprises about 10 to 30 vol % hydrophilic resin.

18. The device of claim 16, wherein the hydrophilic resin comprises polyvinylpyrrolidone.

19. The device of claim 16, wherein the hydrophilic resin comprises an ion exchange resin.

20. The device of claim 16, wherein said hydrophobic polymer comprises a ethylene vinyl acetate copolymer having a vinyl acetate content in the range of about 1 to 40 weight percent.

21. A membrane for controlling agent delivery rom an iontophoretic agent delivery device adapted to deliver the agent through an intact body surface, the device having a reservoir containing the agent to be delivered and being connectable to a source of electrical power for driving the agent from the reservoir and through the body surface, wherein the membrane is interposed between the agent reservoir and the body surface, the membrane permitting electrically-assisted flux (J_EK) of the agent therethrough and substantially preventing passive flux (J_p) of the agent therethrough, the membrane exhibiting a (J_EK +J_p)/J_p ratio of at least about 4, a voltage drop across the membrane of less than about 1 volt, and a J_p of less than about 100 μ

g/hr-cm².

22. The membrane for claim 21, wherein the agent comprises a drug.

24. The membrane of claim 21, comprising a mixture of a hydrophilic resin and a hydrophobic polymer.

25. The membrane of claim 24, wherein the mixture comprises about 10 to 30 vol % hydrophilic resin.

26. The membrane of claim 24, wherein the hydrophilic resin is selected from the group consisting of hydrophilic polymers having an equilibrium water content of at least about 10%.

27. The membrane of claim 26, wherein said hydrophilic resin comprises polyvinylpyrrolidone.

28. The membrane of claim 24, wherein said hydrophilic resin comprises an ion exchange resin.

29. The membrane of claim 28, wherein said ion exchange resin has a functional group selected from the group consisting of sulfonic acid, carboxylic acid, imidodiacetic acid and quaternary amines.

30. The membrane of claim 24, wherein the hydrophobic polymer is selected from the group consisting of polymers having an equilibrium water content of less than about 10%.

31. The membrane of claim 24, wherein said hydrophobic polymer comprises an ethylene vinyl acetate copolymer having a vinyl acetate content in the range of about 1 to 40 weight percent.

32. A membrane for testing performance characteristics of an iontophoretic agent delivery device adapted for delivering an agent through an intact body surface, the device having a reservoir containing the agent to be delivered and being connectable to a source of electrical power for driving the agent from the reservoir and through the body surface, the membrane permitting electrically-assisted flux (J_EK) of the agent therethrough and substantially preventing passive flux (J_p) of the agent therethrough, the membrane exhibiting a (J_EK +J_p)/J_p ratio of at least about 4, a voltage drop across the membrane of less than about 10 volts and a J_p of less than about 100 μ

g/hr-cm².

33. The membrane of claim 32, wherein the agent comprises a drug.

34. The membrane of claim 32, wherein the membrane 11/33 to 12/12 is comprised of a material selected from the group consisting of polycarbonates, polyesters, polyamides, styrene-acrylic acid copolymers, polyurethanes, cellulose esters and polyalkylenes.

35. The membrane of claim 32, comprising a mixture of a hydrophilic resin and a hydrophobic polymer.

36. The membrane of claim 35, wherein the mixture comprises about 10 to 30 vol % hydrophilic resin.

37. The membrane of claim 35, wherein the hydrophilic resin is selected from the group consisting of hydrophilic polymers having an equilibrium water content of at least about 10%.

38. The membrane of claim 37, wherein said hydrophilic resin comprises polyvinylpyrrolidone.

39. The membrane of claim 35, wherein said hydrophilic resin comprises an ion exchange resin.

40. The membrane of claim 38, wherein said ion exchange resin has a functional group selected from the group consisting of sulfonic acid, carboxylic acid, imidodiacetic acid and quaternary amines.

41. The membrane of claim 35, wherein the hydrophobic polymer is selected from the group consisting of polymers having an equilibrium water content of less than about 10%.

42. The membrane of claim 35, wherein the hydrophobic polymer comprises an ethylene vinyl acetate copolymer having a vinyl acetate content in the range of about 1 to 40 weight percent.

43. A method for testing performance characteristics of an iontophoretic agent delivery device adapted for delivering an agent through an intact body surface, the device having a reservoir containing the agent to be delivered and being connectable to a source of electrical power for driving the agent from the reservoir, comprising:

placing the reservoir in agent transmitting relation with one surface of a membrane, the membrane having a second surface opposite the surface which is in agent transmitting relation with the reservoir, which second surface is in contact with an agent collecting medium, the membrane permitting electrically-assisted flux (J_EK) of the agent therethrough and substantially preventing passive flux (J_p) of the agent therethrough, the membrane exhibiting a (J_EK +J_p)/J_p ratio of at least about 4, a voltage drop across the membrane of less than about 10 volts, and a J_p of less than about 100 μ

g/hr-cm² ; and

connecting the source of electrical power to the device and driving the agent through the membrane.

44. The method of claim 43, wherein the agent comprises a drug.

45. The method of claim 43, wherein the membrane 11/33 to 12/12 is comprised of a material selected from the group consisting of polycarbonates, polyesters, polyamides, styrene-acrylic acid copolymers, polyurethanes, cellulose esters and polyalkylenes.

46. The method of claim 43, wherein the membrane comprises a mixture of a hydrophilic resin and a hydrophobic polymer.

47. The method of claim 46, wherein the mixture comprises about 10 to 30 vol % hydrophilic resin.

48. The method of claim 46, wherein the hydrophilic resin is selected from the group consisting of hydrophilic polymers having an equilibrium water content greater than about 10%.

49. The method of claim 46, wherein said hydrophilic resin is polyvinylpyrrolidone.

50. The method of claim 46, wherein said hydrophilic resin is an ion exchange resin.

51. The method of claim 50, wherein said ion exchange resin has a functional group selected from the group consisting of sulfonic acid, carboxylic acid, imidodiacetic acid and quaternary amines.

52. The method of claim 46, wherein the hydrophobic polymer is selected from the group consisting of polymers having an equilibrium water content of less than about 10%.

53. The method of claim 46, wherein the hydrophobic polymer comprises an ethylene vinyl acetate copolymer having a vinyl acetate content in the range of about 1 to 40 weight percent.