Transdermal drug delivery devices having coated microprotrusions
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.
1. 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises;
and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
2. 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 microprotrusions; and
drying said applied aqueous solution to form a dry agent-containing coating on said microprotrusions, 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
3. The method of claim 2 , wherein the coating provides systemic delivery of about 25% to 50% of the agent upon application of the device to the skin of a subject for 5 seconds and wherein the agent comprises desmopressin or hGH.
4. 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, 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
5. 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, 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
6. 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 adrenocorticotropic hormone (ACTH (1-24)), calcitonin, desmopressin, leutinizing hormone releasing hormone (LHRH), goserelin, leuprolide, buserelin, triptorelin, parathyroid hormone (PTH), vasopressin, deamino [Val4, D-Arg8] arginine vasopressin, interferon alpha, interferon beta, interferon gamma, follicle stimulating hormone (FSH), erythoropoietin (EPO), granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukin-10 (IL-10), glucagon, and growth regulatory factor (GRF); 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
7. 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, 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
8. A method of making a device for transdermally delivering a pharmacologically active agent, the method comprising:
providing a member having a plurality of stratus 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
9. 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 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 50 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
10. 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
11. 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
12. 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, 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
13. 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/cm 2 of area of said member, and 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 at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
14. 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/cm 2 of area of said member, and 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 at about 25° C. of greater than about 50 mg/ml and said agent having an aqueous solution having a viscosity at about 25° C. less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.
15. 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, 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 1mg, said agent having an aqueous solubility at about 25° C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25° C. of less than about 500 centipoises; and
wherein the method provides uniformity of coating from microprotrusion to microprotrusion.