Transdermal drug delivery devices having coated microprotrusions

• US 8,663,155 B2
• Filed: 02/02/2006
• Issued: 03/04/2014
• Est. Priority Date: 10/26/2000
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Cormier, Michel J. N., Young, Wendy A., Nyam, Kofi, Daddona, Peter E., Lin, Wei-Qi
• Primary Examiner(s): GULLEDGE, BRIAN M
• Application Number:
  US11/347,779
• Publication Number:
  US 20060200069A1
• Time in Patent Office: 2,952 Days
• Field of Search: None
• US Class Current: 604/46
• 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 passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um, 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 without the use of electricity in an amount less than 1 milligram, said agent having aqueous solubility at 25°

C. of greater than 50 mg/ml and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

2. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, 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, wherein said microprotrusions have a width and thickness ranging from 5 to 50 um;

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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 milligrams/milliliter and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

3. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions being adapted to pierce through the stratum corneum to a depth of less than 500 micrometers, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 milligrams/milliliter and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

4. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 milligrams/milliliter and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

5. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

6. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um, 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 milligrams/milliliter and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

7. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 milligrams/milliliter and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises; and

wherein the pharmacologically active agent is selected from the group consisting of adrenocortiocotropic hormone (ACTH (1-24)), calcitonin, desmopressin, leutinizing hormone releasing hormone (LHRH), goserelin, leuprolide, buserelin, triptorelin, other LHRH analogs, parathyroid hormone (PTH), vasopressin, deamino [Val4, D-Arg8] arginine vasopressin, interferon alpha, interferon beta, interferon gamma, follicle stimulating hormone (FSH), erythropoietin (EPO), granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukin-10 (IL-10), glucagon, growth regulatory factor (GRF), analogs thereof and pharmaceutically acceptable salts thereof, wherein said device further comprises a spring-loaded impact applicator.

8. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 milligrams/milliliter and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

9. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 milligrams/milliliter and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

10. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 milligrams/milliliter and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

11. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 10 picoliters to about 200 picoliters;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 milligrams/milliliter and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

12. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 mg/ml and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

13. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 without the use of electricity in an amount less than 0.25 milligrams, said agent having aqueous solubility at 25°

C. of greater than 50 mg/ml and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

14. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 mg/ml and said aqueous solution having a viscosity at 25°

C. of less than 50 centipoises, wherein said device further comprises a spring-loaded impact applicator.

15. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 50 micrometers;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 mg/ml and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

16. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 25 micrometers;

wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 milligrams/milliliter and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoises, wherein said device further comprises a spring-loaded impact applicator.

17. A passive transdermal drug delivery system comprising a device for transdermally delivering a pharmacologically active agent via passive diffusion, the device comprising:

a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a width and thickness ranging from 5 to 50 um; 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 without the use of electricity in an amount less than 1 mg, said agent having aqueous solubility at 25°

C. of greater than 50 mg/mL and said aqueous solution having a viscosity at 25°

C. of less than 500 centipoise, wherein said device further comprises a spring-loaded impact applicator.