Temperature modulation of transdermal drug delivery

• US 20060135911A1
• Filed: 12/14/2005
• Published: 06/22/2006
• Est. Priority Date: 12/17/2004
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Mittur, Aravindkumar
• Application Number:
  US11/304,335
• Publication Number:
  US 20060135911A1
• Time in Patent Office: Days
• US Class Current: 604/113
• CPC Class Codes: A61F 2007/0001 Body part
• CPC Class Codes: A61F 2007/0075 using a Peltier element, e.g. near the spot to be heated or cooled
• CPC Class Codes: A61F 7/007 characterised by electric heating
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04

Abstract

A trans-body-surface drug delivery device for the administration of at least one drug to an individual at a therapeutically effective rate. The device including a reservoir having at least one drug and a thermoeffector having a first surface that is controllable to at least one of heating and cooling the reservoir to affect passage rate of the drug through the body surface.

Claims

1. A device for the administration of a pharmaceutical agent to an individual at a therapeutically effective rate, by passing through a body surface, comprising:

a reservoir including a pharmaceutical agent and a thermoeffector having a first surface proximate the reservoir, the first surface controllable to at least one of heating and cooling the reservoir to affect passage rate of the pharmaceutical agent through the body surface.

2. The device of claim 1 wherein the first surface faces the reservoir and is controllable to reversibly heat or cool.

3. The device of claim 1 wherein the thermoeffector can be controlled to reverse heat flow to the reservoir, thereby modulating delivery of the pharmaceutical agent from the reservoir.

4. The device of claim 1 wherein the first surface faces the reservoir and is controllable to reversibly heat or cool and the device has a second surface that heats while the first surface cools and cools while the first surface heats.

5. The device of claim 4 wherein the thermoeffector includes a plate having the first surface proximate the reservoir and having the second surface facing away from the reservoir, the plate having a thickness less than a thickness of the reservoir.

6. The device of claim 5 wherein the thermoeffector plate includes multiple layers, at least one of which includes semiconductor material having a junction that can either heat or cool depending on direction of electrical current passing therethrough.

7. The device of claim 6 wherein the thermoeffector plate includes two insulation layers with an array of Bismuth-containing semiconductor elements positioned therebetween.

8. The device of claim 7 wherein the thermoeffector plate has a thickness of less than 4 mm.

9. The device of claim 7 wherein the thermoeffector plate has a thickness of between 1 mm and 4 mm.

10. The device of claim 6 comprising a feedback control for controlling the temperature of the reservoir.

11. The device of claim 6 further comprising a matrix having heat sensitive polymer in the reservoir, the heat sensitive polymer causing the matrix to change size by swelling and shrinking as a function of temperature such that the matrix upon swelling increases the matrix capacity to hold liquid and upon shrinking decreases capacity to hold liquid.

12. The device of claim 11 further comprising hydrogel in the reservoir, the hydrogel being adapted to shrink as the temperature falls and swell as the temperature rises.

13. The device of claim 11 further comprising hydrogel in the reservoir, the hydrogel being adapted to shrink as the temperature rises and swell as the temperature falls.

14. The device of claim 11 wherein the hydrogel contains a polymer selected from a group consisting of poly(N-isopropylacrylamide), copolymer containing poly(N-isopropylacrylamide), and polypeptide-containing polymers.

15. The device of claim 11 wherein the hydrogel contains a polymer selected from a group consisting of poly(N-isopropylacrylamide) homopolymer, poly(N-isopropylacrylamide)acrylamide copolymer, copolymer of poly(N-isopropylacrylamide) containing silane monomers selected from [3-(methacryloyloxy)propyl]trimethoxysilane, [2-(methacryloyloxy)ethoxy]-trimethylsilane and methacryloyloxy)trimethylsilane, copolymer of poly(hydroxypropyl methacrylamide), dicarboxymethylaminopropyl methacrylamide with protein moieties, xyloglucan, ethyl(hydroxyethyl)cellulose, poly(ethyleneoxide-b-propylene oxide-b-ethylene oxide) and its copolymers, poly(ethylene oxide)/(D,L-lactic acid-co-glycolic acid)copolymers, combinations of chitosan and polyol salts, poly(silamine), and poly(organophosphazene)derivatives.

16. The device of claim 11 comprising circuitry that causes the matrix to swell and circuitry that causes the matrix to shrink.

17. The device of claim 10 comprising circuitry that causes the matrix to shrink and then swells after one of reaching a specific time and reaching a specified temperature at the reservoir.

18. The device of claim 10 wherein the device does not include a sharp object that punctures through the body surface into the tissue beneath the body surface.

19. The device of claim 4 further comprising electrode contacting the reservoir to provide an electrical potential to drive the pharmaceutical agent through the body surface by electrotransport.

20. A method for making a device for trans-body-surface delivery of pharmaceutical agent, comprising:

forming a reservoir including a pharmaceutical agent and positioning a thermoeffector proximate to the reservoir, the thermoeffector having a first surface that is controllable to at least one of heating and cooling the reservoir to affect trans-body-surface passage rate of the pharmaceutical agent.

21. The method of claim 20 comprising positioning the first surface to the reservoir and wherein the thermoeffector is controllable to reversibly heat or cool and the device has a second surface that heats while the first surface cools and cools while the first surface heats.

22. The method of claim 21 wherein the thermoeffector includes a plate having the first and second surfaces and the method comprising placing the plate with the first surface proximate the reservoir and having the second surface facing away from the reservoir, the plate having a thickness less than a thickness of the reservoir.

23. The method of claim 22 wherein the plate includes semiconductor material having a junction that can either heat or cool depending on direction of electrical current passing therethrough, and the method includes positioning an array of Bismuth containing semiconductor elements between two insulation layers.

24. The method of claim 23 further comprising including a matrix in the reservoir, the matrix having thermosensitive polymer that causes the matrix to swell and shrink as a function of temperature.

25. The method of claim 20 further comprising including hydrogel in the reservoir, the hydrogel being adapted to one of shrinking and swelling as the temperature falls and reversing the shrinking or swelling as the temperature rises.

26. The method of claim 20 comprising including in the hydrogel a polymer selected from a group consisting of poly(N-isopropylacrylamide), copolymer containing poly(N-isopropylacrylamide), and polypeptide containing polymers.

27. The method of claim 20 comprising including in the hydrogel a polymer selected from a group consisting of poly(N-isopropylacrylamide)homopolymer, poly(N-isopropylacrylamide)acrylamide copolymer, copolymer of poly(N-isopropylacrylamide) containing silane monomers including [3-(methacryloyloxy)propyl]trimethoxysilane, [2-(methacryloyloxy)ethoxy]-trimethylsilane and methacryloyloxy)trimethylsilane, copolymer of poly(hydroxypropyl methacrylamide) and dicarboxymethylaminopropyl methacrylamide with protein moieties, xyloglucan, ethyl(hydroxyethyl)cellulose, poly(ethyleneoxide-b-propylene oxide-b-ethylene oxide) and its copolymers, poly(ethylene oxide)/(D,L-lactic acid-co-glycolic acid)copolymers, combinations of chitosan and polyol salts, poly(silamine), and poly(organophosphazene) derivatives.

28. The method of claim 20 comprising including a heat sensitive polymer in the reservoir such that the matrix upon cooling swells to increase the matrix capacity to hold liquid and upon heating shrinks to decrease capacity to hold liquid.

29. The method of claim 21 further comprising placing an electrode at the reservoir to provide an electrical potential to drive the pharmaceutical agent through the body surface by electrotransport.

30. A method for trans-body-surface delivery of pharmaceutical agent, comprising:

providing a reservoir including a pharmaceutical agent and actively reversibly heating the reservoir to affect passage rate of the pharmaceutical agent.

31. The method of claim 30, wherein the thermoeffector has a first surface and a second surface, and comprising positioning the first surface of thermoeffector thermoconductively proximate to the reservoir and effect a temperature change on the first surface while effecting a temperature change on the second surface opposite to that on the first surface.

32. The method of claim 30 wherein the thermoeffector includes semiconductor material having a junction that can either heat or cool depending on direction of electrical current passing therethrough, and the method includes passing a current through an array of Bismuth-containing semiconductor elements that are positioned between two insulation plates.

33. The method of claim 31 further comprising swelling and shrinking a hydrogel in the reservoir as a fiction of temperature.

34. The method of claim 31 further comprising swelling and shrinking a hydrogel in the reservoir, the hydrogel shrinks as the temperature rises and swells as the temperature falls.

35. The method of claim 31 comprising including swelling and shrinking a hydrogel in the reservoir, the hydrogel including a polymer selected from a group consisting of poly(N-isopropylacrylamide), copolymer containing poly(N-isopropylacrylamide), and polypeptide-containing polymers.

36. The method of claim 30 comprising electrically causing the matrix to shrink to provide liquid on the body surface and then electrically causing the matrix to swell to absorb liquid from the body surface.

37. The method of claim 30 comprising delivering the pharmaceutical agent without using a sharp object that punctures through the body surface into the tissue beneath the body surface.

38. The method of claim 30 further providing an electrical potential to drive the pharmaceutical agent through the body surface by electrotransport.

44. The device of claim 30 comprising circuitry that causes the matrix to shrink and then after one of reaching a specific time and reaching a specified temperature at the reservoir causes the matrix to swell.

39. A device for the administration a liquid to an object surface, comprising:

a liquid in a matrix and a thermoeffector having a first surface that is actively reversibly controllable to heat and controllable to cool to cause the matrix to change volume, thereby controlling the amount of liquid being deposited on the body surface.

40. The device of claim 39 wherein the first surface faces the matrix and is controllable to reversibly heat or cool, whereby heating causes the matrix to shrink and cooling causes the matrix to swell.

41. The device of claim 39 wherein the thermoeffector has a plate including multiple layers, at least one of which includes semiconductor material having a junction that can either heat or cool depending on direction of electrical current passing therethrough.

42. The device of claim 39 wherein the thermoeffector has a plate that includes two insulation layers with an array of Bismuth-containing semiconductor elements positioned therebetween.

43. The device of claim 40 comprising circuitry that causes heating the matrix by heat conduction to cause the matrix to shrink and circuitry that cools the matrix by heat conduction to cause the matrix to swell.

45. A device for the administration of a pharmaceutical agent to an individual at a therapeutically effective rate, by passing through a body surface, comprising:

a matrix including a pharmaceutical agent and a thermoeffector having a first surface proximate the matrix, the first surface controllable to reversibly heat and cool the matrix to affect passage rate of the pharmaceutical agent through the body surface, the thermoeffector having a second surface that heats while the first surface cools and cools while the first surface heats, the thermoeffector having multiple layers including at least one layer having Bismuth-containing semiconductor material with a junction that can either heat or cool depending on the direction of electrical current passing through, wherein the heating and cooling of the matrix changes the matrix'"'"'s capacity to hold a liquid containing the pharmaceutical agent.

46. A method of using of a composition comprising a drug, together with a carrier, the composition releasing the drug in a controllable dose over time, the carrier having a reservoir containing the composition and having a thermoeffector proximate the reservoir, comprising controlling the thermoeffector for reversibly heating the reservoir to control release of the drug to deliver through a body surface of a patient.