Transdermal delivery system for dried particulate or lyophilized medications

• US 7,363,075 B2
• Filed: 01/05/2006
• Issued: 04/22/2008
• Est. Priority Date: 10/31/2002
• Status: Active Grant

• Current Assignee: Syneron Medical Limited (Syneron Incorporated)
• Original Assignee: TransPharma Medical Ltd. (Syneron Incorporated)
• Inventors: Stern, Meir, Levin, Galit
• Primary Examiner(s): Weber; Jon
• Assistant Examiner(s): Tsay; Marsha
• Application Number:
  US11/327,016
• Publication Number:
  US 20060121104A1
• Time in Patent Office: 838 Days
• Field of Search: 424/449, 424/447, 606/167, 604/20, 600/372, 530/303
• US Class Current: 604/20
• 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 system for transdermal delivery of a peptide or polypeptide from a dried pharmaceutical composition comprising:

(i) an apparatus for facilitating transdermal delivery of a peptide or polypeptide through skin of a subject, said apparatus comprises;

(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 ablation of stratum corneum in an area beneath the electrode, thereby generating at least one micro-channel in the area on the skin of the subject; and

(ii) a patch comprising a non-adhesive liner and a dried pharmaceutical composition comprising a peptide or polypeptide having up to two hundred amino acid residues, wherein the dried pharmaceutical composition is present upon the non-adhesive liner.

2. The system according to claim 1, wherein the peptide is calcitonin.

3. The system according to claim 2, wherein the peptide is salmon calcitonin.

4. The system according to claim 1, wherein the peptide is parathyroid hormone (PTH).

5. The system according to claim 4, wherein the peptide is human PTH (hPTH).

6. The system according to claim 5, wherein the peptide is hPTH (1-34).

7. The system according to claim 1, wherein the pharmaceutical composition further comprises a stabilizer.

8. The system according to claim 7, wherein the stabilizer is a carbohydrate selected from the group consisting of glucose, galactose, raffinose, cellobiose, gentiobiose, sucrose and trehalose.

9. The system according to claim 1, wherein the pharmaceutical composition further comprises an acidic component to yield a pH in the range from about 3 to about 6 in solution before drying.

10. The system according to claim 9, wherein the pharmaceutical composition comprises hPTH (1-34), sucrose and acetic acid to yield a pH of about 4.0 in solution before drying.

11. The system according to claim 9, wherein the pharmaceutical composition comprises hPTH (1-34), trehalose and citric acid to yield a pH of about 4.0 in solution before drying.

12. The system of claim 1, wherein the patch is a printed patch comprising a uniform distribution of dried solid dots of the pharmaceutical composition present upon the non-adhesive liner.

13. The system according to claim 12, wherein the peptide is calcitonin.

14. The system according to claim 13, wherein the peptide is salmon calcitonin.

15. The system according to claim 12, wherein the peptide is parathyroid hormone (PTH).

16. The system according to claim 15, wherein the peptide is human PTH (hPTH).

17. The system according to claim 16, wherein the peptide is hPTH (1-34).

18. The system according to claim 12, wherein the pharmaceutical composition further comprises a stabilizer.

19. The system according to claim 18, wherein the stabilizer is a carbohydrate selected from the group consisting of glucose, galactose, raffinose, cellobiose, gentiobiose, sucrose and trehalose.

20. The system according to claim 12, wherein the pharmaceutical composition further comprises an acidic component to yield a pH in the range from about 3 to about 6 in solution before drying.

21. The system according to claim 20, wherein the pharmaceutical composition comprises hPTH (1-34), sucrose and acetic acid to yield a pH of about 4.0 in solution before drying.

22. The system according to claim 20, wherein the pharmaceutical composition comprises hPTH (1-34), trehalose and citric acid to yield a pH of about 4.0 in solution before drying.

23. A method for transdermal administration of a dried pharmaceutical composition comprising a peptide or polypeptide by the system of claim 1, the method comprising:

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

(b) affixing the patch upon the micro-channel generated area to administer the pharmaceutical composition by dissolving it in fluids that are exuded from the skin through the micro-channel(s).

24. The method according to claim 23 further comprising:

(c) achieving a therapeutic blood concentration of the peptide or polypeptide for a predetermined period of time.

25. The method according to claim 23, wherein the peptide is calcitonin.

26. The method according to claim 25, wherein the peptide is salmon calcitonin.

27. The method according to claim 23, wherein the peptide is parathyroid hormone (PTH).

28. The method according to claim 27, wherein the peptide is human PTH.

29. The method according to claim 28, wherein the peptide is hPTH (1-34).

30. The system according to claim 1, wherein the electrode cartridge is removable.

31. The system according to claim 1, wherein the electrode cartridge comprises a plurality of electrodes.

32. The system according to claim 1, wherein the electrical energy is at radio frequency.

33. The method according to claim 23, wherein the pharmaceutical composition further comprises a stabilizer.

34. The method according to claim 33, wherein the stabilizer is a carbohydrate selected from the group consisting of glucose, galactose, raffinose, cellobiose, gentiobiose, sucrose and trehalose.

35. The method according to claim 23, wherein the pharmaceutical composition further comprises an acidic component to yield a pH in the range from about 3 to about 6 in solution before drying.

36. The method according to claim 35, wherein the pharmaceutical composition comprises hPTH (1-34), sucrose and acetic acid to yield a pH of about 4.0 in solution before drying.

37. The method according to claim 35, wherein the pharmaceutical composition comprises hPTH (1-34), trehalose and citric acid to yield a pH of about 4.0 in solution before drying.

38. The method according to claim 23, wherein the patch is a printed patch comprising a uniform distribution of dried solid dots of the pharmaceutical composition present on the non-adhesive liner.

39. The method according to claim 38, wherein the peptide is calcitonin.

40. The method according to claim 39, wherein the peptide is salmon calcitonin.

41. The method according to claim 38, wherein the peptide is parathyroid hormone (PTH).

42. The method according to claim 41, wherein the peptide is human PTH (hPTH).

43. The method according to claim 42, wherein the peptide is hPTH (1-34).

44. The method according to claim 38, wherein the pharmaceutical composition further comprises a stabilizer.

45. The method according to claim 44, wherein the stabilizer is a carbohydrate selected from the group consisting of glucose, galactose, raffinose, cellobiose, gentiobiose, sucrose and trehalose.

46. The method according to claim 38, wherein the pharmaceutical composition further comprises an acidic component to yield a pH in the range from about 3 to about 6 in solution before drying.

47. The method according to claim 46, wherein the pharmaceutical composition comprises hPTH (1-34), sucrose and acetic acid to yield a pH of about 4.0 in solution before drying.

48. The method according to claim 46, wherein the pharmaceutical composition comprises hPTH (1-34), trehalose and citric acid to yield a pH of about 4.0 in solution before drying.