Transdermal delivery system for dried particulate or lyophilized medications

• US 7,335,377 B2
• Filed: 10/31/2003
• Issued: 02/26/2008
• Est. Priority Date: 10/31/2002
• Status: Expired due to Fees

• Current Assignee: Syneron Medical Limited (Syneron Incorporated)
• Original Assignee: TransPharma Medical Ltd. (Syneron Incorporated)
• Inventors: Stern, Meir, Levin, Galit
• Primary Examiner(s): Monshipouri; Maryam
• Assistant Examiner(s): TSAY, MARSHA M
• Application Number:
  US10/699,582
• Publication Number:
  US 20040137044A1
• Time in Patent Office: 1,579 Days
• Field of Search: 424/449, 424/447, 606/167, 514/254.1, 604/20, 600/372, 530/303
• US Class Current: 424/447
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61K 9/703 characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• 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
• CPC Class Codes: A61N 1/0416 Anode and cathode
• CPC Class Codes: A61N 1/0476 Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

The present invention provides a system for transdermal delivery of dried or lyophilized pharmaceutical compositions and methods using thereof. The system comprises an apparatus for facilitating transdermal delivery of an agent that generates hydrophilic micro-channels, and a patch comprising a therapeutically active agent. The present invention is useful for transdermal delivery of hydrophilic agents, particularly of high molecular weight proteins.

Claims

1. A printed patch for transdermal administration of at least one therapeutically active agent comprising a non-adhesive liner and a dried pharmaceutical composition that comprises the active agent or agents present on the non-adhesive liner, wherein the non-adhesive liner is made of a material that is not permeable to the active agent or agents.

2. The printed patch according to claim 1 wherein the patch further comprises at least one layer selected from the group consisting of a backing layer, an adhesive and a microporous liner layer.

3. The printed patch according to claim 1 wherein the dried pharmaceutical composition is hydrophilic.

4. The printed patch according to claim 3 wherein the dried pharmaceutical composition comprises at least one hydrophilic therapeutically active agent.

5. The printed patch according to claim 4 wherein the hydrophilic therapeutically active agent is selected from the group consisting of proteins, polypeptides, peptides, polynucleotides, oligonucleotides, growth factors, hormones, and salts thereof.

6. The printed patch according to claim 5 wherein the hydrophilic therapeutically active agent is human growth hormone.

7. The printed patch according to claim 5 wherein the hydrophilic therapeutically active agent is human insulin.

8. The printed patch according to claim 4 wherein the dried pharmaceutical composition further comprises at least one additional hydrophilic agent.

9. The printed patch according to claim 8 wherein the hydrophilic agent is mannitol.

10. The printed patch according to claim 8 wherein the dried pharmaceutical composition comprises human growth hormone and mannitol.

11. The printed patch according to claim 8 wherein the dried pharmaceutical composition further comprises a stabilizer.

12. The printed patch according to claim 11 wherein the stabilizer is selected from carbohydrates, amino acids, and polymers.

13. The printed patch according to claim 12 wherein the carbohydrate is a disaccharide selected from sucrose and trehalose.

14. The printed patch according to claim 11 wherein the dried pharmaceutical composition comprises human growth hormone, mannitol and sucrose.

15. The printed patch according to claim 11 wherein the dried pharmaceutical composition comprises human growth hormone, mannitol and trehalose.

16. The printed patch according to claim 1, which contains below 20% by weight of water and wherein the active agent remains stable for at least three months at about 22°

C.

17. The printed patch according to claim 1 wherein the pharmaceutical composition further comprises at least one component selected from an anti-oxidant, a buffering agent and a preservative.

18. A method for transdermal administration of a dried pharmaceutical composition comprising at least one therapeutically active agent comprising:

(a) generating at least one micro-channel in an area of the skin of a subject, and

(b) affixing a printed patch according to claim 1 to the area of skin in which at least one micro-channel is present.

19. The method according to claim 18 which further comprises:

(c) achieving a therapeutic blood concentration of the active agent for a predetermined period of time.

20. The method according to claim 18 wherein the dried pharmaceutical composition is hydrophilic.

21. The method according to claim 20 wherein the dried pharmaceutical composition comprises at least one hydrophilic therapeutically active agent.

22. The method according to claim 21 wherein the hydrophilic therapeutically active agent is selected from the group consisting of proteins, polypeptides, peptides, polynucleotides, oligonucleotides, growth factors, hormones, and salts thereof.

23. The method according to claim 22 wherein the hydrophilic therapeutically active agent is human growth hormone.

24. The method according to claim 23 wherein the predetermined period of time is about 1 to 6 hours.

25. The method according to claim 22 wherein the therapeutically hydrophilic active agent is human insulin.

26. The method according to claim 25 wherein the predetermined period of time is about 4 to 6 hours.

27. The method according to claim 18 wherein the patch comprises at least two electrodes integrated thereto.

28. The method according to claim 18 comprising inducing iontophoresis of the at least one therapeutically active agent into the skin of the subject.

29. The method according to claim 28 wherein inducing the iontophoresis comprises inducing the iontophoresis subsequent to the generating of the at least one micro-channel.

30. The printed patch according to claim 1 comprising at least two electrodes integrated thereto.

31. A system for transdermal delivery of an active therapeutic agent from a dried pharmaceutical composition comprising:

an apparatus for facilitating transdermal delivery of an active therapeutic agent through skin of a subject, said apparatus capable of generating at least one micro-channel in an area on the skin of the subject, and the printed patch according to claim 1.

32. The system according to claim 31 wherein the patch further comprises at least one layer selected from the group consisting of a backing layer, and an adhesive layer and a microporous liner layer.

33. The system according to claim 31 wherein the dried pharmaceutical composition is hydrophilic.

34. The system according to claim 33 wherein the dried pharmaceutical composition comprises at least one hydrophilic therapeutically active agent.

35. The system according to claim 34 wherein the hydrophilic therapeutically active agent is selected from the group consisting of proteins, polypeptides, peptides, polynucleotides, oligonucleotides, growth factors, hormones, and salts thereof.

36. The system according to claim 35 wherein the hydrophilic therapeutically active agent is human growth hormone.

37. The system according to claim 35 wherein the hydrophilic therapeutically active agent is human insulin.

38. The system according to claim 34 wherein the dried pharmaceutical composition further comprises at least one additional hydrophilic agent.

39. The system according to claim 38 wherein the hydrophilic agent is mannitol.

40. The system according to claim 38 wherein the dried pharmaceutical composition comprises human growth hormone and mannitol.

41. The system according to claim 38 wherein the dried pharmaceutical composition further comprises a stabilizer.

42. The system according to claim 41 wherein the stabilizer is selected from carbohydrates, amino acids and polymers.

43. The system according to claim 42 wherein the carbohydrate is a disaccharide selected from sucrose and trehalose.

44. The system according to claim 41 wherein the pharmaceutical composition comprises human growth hormone, mannitol and sucrose.

45. The system according to claim 41 wherein the pharmaceutical composition comprises human growth hormone, mannitol and trehalose.

46. The system according to claim 31 wherein the active agent remains stable for at least three months at about 22°

C.

47. The system according to claim 31 wherein the pharmaceutical composition further comprises at least one component selected from an anti-oxidant, a buffering agent and a preservative.

48. The system according to claim 31 comprising an apparatus for facilitating transdermal delivery of a therapeutically active agent through skin of a subject, said apparatus comprising:

a. an electrode cartridge comprising at least one electrode; and

b. a main unit comprising a control unit which is adapted to apply electrical energy to the electrode when the electrode is in vicinity of the skin, typically generating current flow or one or more sparks, enabling to cause ablation of stratum corneum in an area beneath the electrode, thereby generating at least one micro-channel.

49. The system according to claim 48 wherein the electrode cartridge is removable.

50. The system according to claim 48 wherein the electrode cartridge comprises a plurality of electrodes capable of generating a plurality of micro-channels of uniform shape and dimensions.

51. The system according to claim 48 wherein the electrical energy is of radio frequency.

52. The system according to claim 31, wherein the printed patch comprises at least two electrodes.

53. The system according to claim 52, wherein the electrodes are adapted to induce iontophoresis of the at least one therapeutically active agent into the skin of the subject.