Transdermal drug delivery devices having coated microprotrusions

• US 20020128599A1
• Filed: 10/26/2001
• Published: 09/12/2002
• Est. Priority Date: 10/26/2000
• Status: Active Grant

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Daddona, Peter E., Young, Wendy A., Cormier, Michel J.N., Nyam, Kofi
• Granted Patent: US 7,537,795 B2
• Time in Patent Office: Days
• US Class Current: 604/116
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles

Abstract

A device (12) and method are provided for percutaneous transdermal delivery of a potent pharmacologically active agent. The agent is dissolved in water to form an aqueous coating solution having an appropriate viscosity for coating extremely tiny skin piercing elements (10). The coating solution is applied to the skin piercing elements (10) using known coating techniques and then dried. The device (12) is applied to the skin of a living animal (e.g., a human), causing the microprotrusions (10) to pierce the stratum corneum and deliver a therapeutically effect dose of the agent to the animal.

Claims

1. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 milligrams, said agent having aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

2. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions and

a dry coating only on one or more of said microprotrusions;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises.

3. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusion being adapted to pierce through the stratum corneum to a depth of less than about 500 micrometers; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises.

4. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;

said coating having a thickness equal to or less than the thickness of the microprotrusions;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises.

5. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a length of less than 500 micrometers and a thickness of less than 25 micrometers; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises.

6. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having been formed by etching said plurality of microprotrusions from a thin sheet and folding the microprotrusions out of a plane of the sheet; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises.

7. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;

said pharmacologically active agent being sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises; and

wherein the pharmacologically active agent is selected from the group consisting of ACTH (1-24), calcitonin, desmopressin, LHRH, goserelin, leuprolide, buserelin, triptorelin, other LHRH analogs, PTH, vasopressin, deamino [val4, D-Arg8] arginine vasopressin, interferon alpha, interferon beta, interferon gamma, FSH, EPO, GM-CSF, G-CSF, IL-10, glucagon, GRF, analogs thereof and pharmaceutically acceptable salts thereof.

8. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of the pharmacologically active agent desmopressin;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises.

9. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating having been applied by dip coating;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises.

10. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating having been applied by spray coating;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises.

11. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating having been applied by spray coating;

said spray comprising droplets having a volume of about 10 picoliters to about 200 picoliters;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises.

12. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry non-contiguous coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

13. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 0.25 milligrams, said agent having aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

14. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 50 centipoises.

15. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating having a thickness over a surface of said member of less than about 50 micrometers;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

16. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating having a thickness over a surface of said member of less than about 25 micrometers;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity less than about 500 centipoises.

17. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions; and

a dry coating on said member;

said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent and an adjuvant;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

18. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

19. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto only one or more of said microprotrusions; and

drying said applied aqueous solution to form a dry agent-containing coating only on one or more of said microprotrusions;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

20. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

said microprotrusions adapted to pierce through the stratum corneum to a depth of less than about 500 micrometers;

applying an aqueous solution of the pharmacologically active agent onto the member; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

21. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member; and

drying said applied aqueous solution to form a dry agent-containing coating on said member, said coating being less than a thickness of the microprotrusions.

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

22. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a length of less than 500 micrometers and a thickness of less than 25 micrometers;

applying an aqueous solution of the pharmacologically active agent onto the member; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

23. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member;

said pharmacologically active agent selected from the group consisting of ACTH (1-24), calcitonin, desmopressin, LHRH, goserelin, leuprolide, buserelin, triptorelin, other LHRH analogs, PTH, vasopressin, deamino [Val4, D-Arg8] arginine vasopressin, interferon alpha, interferon beta, interferon gamma, FSH, EPO, GM-CSF, G-CSF, IL-10, glucagon, GRF, analogs thereof and pharmaceutically acceptable salts thereof; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

24. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent desmopressin onto the member; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein said agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

25. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto said member by dip coating said member in said solution; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

26. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member by spray coating;

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

27. A device for transdermally delivering a pharmacologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions and

a dry coating on said member, the coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating being applied by spray coating;

said spray comprising droplets having a volume of about 10 picoliters to about 200 picoliters;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

28. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member in a non-contiguous pattern; and

drying said applied aqueous solution to form a dry agent-containing non-contiguous coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

29. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member;

said pharmacologically active agent being sufficiently potent to be therapeutically effective when administered in an amount less than about 0.25 milligrams and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

30. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein said agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 50 centipoises.

31. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

said coating having a thickness over a surface of said member of less than 50 micrometers;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

32. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

said coating having a thickness over a surface of said member of less than 25 micrometers;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

33. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

providing an aqueous solution comprising said pharmacologically active agent and an adjuvant;

applying said aqueous solution onto the member; and

drying said applied aqueous solution to form a dry agent-containing and adjuvant-containing coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

34. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

said coating comprising a loading of said pharmacologically active agent of less than 1 mg/cm² of area of said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

35. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

said coating comprising a loading of said pharmacologically active agent of less than 0.5 mg/cm² of area of said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

36. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member using a microfluid deposition technique; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.

37. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:

providing a member having a plurality of stratum corneum-piercing microprotrusions;

applying an aqueous solution of the pharmacologically active agent onto the member using an inkjet printing technique; and

drying said applied aqueous solution to form a dry agent-containing coating on said member;

wherein the agent is sufficiently potent to be therapeutically effective when administered in an amount of less than about 1 mg, said agent having an aqueous solubility of greater than about 50 mg/ml and said aqueous solution having a viscosity less than about 500 centipoises.