Transdermal delivery system for dried particulate or lyophilized medications

• US 20060233871A1
• Filed: 03/27/2006
• Published: 10/19/2006
• 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
• Granted Patent: US 7,383,084 B2
• Time in Patent Office: Days
• US Class Current: 424/449
• 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: 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: 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 1/042 Material of the electrode
• CPC Class Codes: A61N 1/0436 Material of the electrode
• 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:

an apparatus for facilitating transdermal delivery of a peptide or polypeptide through skin of a subject, wherein the apparatus is capable of generating a plurality of micro-channels in an area on the skin of the subject, and a patch comprising a dried pharmaceutical composition comprising a peptide or polypeptide having up to two hundred amino acid residues.

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

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

4. The system according to claim 1, wherein the peptide or polypeptide is parathyroid hormone (PTH) or a fragment thereof.

5. The system according to claim 4, wherein PTH is human PTH (1-34).

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

7. The system according to claim 6, wherein the stabilizer is a simple or complex carbohydrate.

8. The system according to claim 7, wherein the simple or complex carbohydrate is selected from the group consisting of mannose, 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. A printed patch comprising a dried pharmaceutical composition comprising a peptide or polypeptide having up to two hundred amino acid residues.

11. The printed patch according to claim 10, wherein the peptide or polypeptide is calcitonin.

12. The printed patch according to claim 11, wherein calcitonin is salmon calcitonin.

13. The printed patch according to claim 10, wherein the peptide or polypeptide is parathyroid hormone (PTH) or a fragment thereof.

14. The printed patch according to claim 13, wherein PTH is human PTH (1-34).

15. The printed patch according to claim 10, wherein the pharmaceutical composition further comprises a stabilizer.

16. The printed patch according to claim 15, wherein the stabilizer is a simple or complex carbohydrate.

17. The printed patch according to claim 16, wherein the simple or complex carbohydrate is selected from the group consisting of mannose, glucose, galactose, raffinose, cellobiose, gentiobiose, sucrose and trehalose.

18. The printed patch according to claim 10, 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.

19. A method for transdermal administration of a dried pharmaceutical composition comprising a peptide or polypeptide, the method comprising:

(a) generating a plurality of micro-channels in an area of the skin of a subject;

(b) affixing a printed patch to the area of the skin of the subject, the printed patch comprising a dried pharmaceutical composition comprising a therapeutically effective amount of peptide or polypeptide having up to two hundred amino acid residues; and

(c) achieving dose efficiency of at least 10%.

20. The method of claim 19, wherein the peptide or polypeptide is calcitonin.

21. The method of claim 20, wherein calcitonin is salmon calcitonin.

22. The method of claim 19, wherein the peptide or polypeptide is parathyroid hormone (PTH) or a fragment thereof.

23. The method of claim 22, wherein PTH is human PTH (1-34).

24. The method of claim 23, wherein the subject is human.