Method and device for transdermal delivery of parathyroid hormone using a microprojection array

• US 9,687,641 B2
• Filed: 05/04/2011
• Issued: 06/27/2017
• Est. Priority Date: 05/04/2010
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: Corium International, Inc.
• Inventors: Singh, Parminder, Chen, Guohua, Bairamov, Danir, Worsham, Robert Wade
• Primary Examiner(s): Sirmons, Kevin C
• Assistant Examiner(s): Hall, Deanna K
• Application Number:
  US13/101,071
• Publication Number:
  US 20110276028A1
• Time in Patent Office: 2,246 Days
• Field of Search: 604 46, 604506, 604289, 604290, 604307
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61P 19/10 for osteoporosis

Abstract

A method and a drug delivery system for transdermally administering parathyroid hormone (PTH) in a pulsatile fashion are provided, where the drug delivery system comprises an array of microprojections each comprising PTH.

Claims

1. A method of transdermally administering a dose of PTH to a mammalian subject, comprising:

applying to a skin site of a subject a microprotusion array comprising a plurality of microprotrusions extending from an approximately planar base, each microprotrusion comprising an end portion distal to the base and an upper portion proximal to the base, the end portion comprising a tip of the microprotrusion, at least the end portion comprising parathyroid hormone (PTH) in a water-soluble polymer matrix,

inserting all or a portion of the plurality of microprotrusions into the skin, and

maintaining the array on the skin site for 15 minutes or less, whereby at least a portion of the end portions including the tip of the plurality of microprotrusions detach from the microprotrusion array;

whereby the method achieves an average time to maximum PTH plasma concentration (T_max) of about ten minutes or less.

2. The method of claim 1, wherein the PTH is human parathyroid hormone (1-34).

3. The method of claim 1, wherein the water-soluble polymer matrix comprises a sugar selected from the group consisting of dextran and sorbitol.

4. The method of claim 3, wherein the water-soluble matrix further comprises a buffer selected from the group consisting of histidine and histidine hydrochloride.

5. The method of claim 1, wherein the base is comprised of a water-insoluble polymer.

6. The method of claim 5, wherein the upper portion of each microprotrusion is comprised of the water-insoluble polymer.

7. The method of claim 5, wherein the water-insoluble polymer comprises a poly(lactic acid-co-glycolic acid).

8. The method of claim 6, wherein the water-insoluble polymer comprises a poly(lactic acid-co-glycolic acid).

9. The method of claim 1, wherein the end portion and the upper portion of each microprotrusion are comprised of the same water-soluble polymer.

10. The method of claim 5, wherein the end portion and the upper portion of each microprotrusion are comprised of the same water-soluble polymer.

11. The method of claim 1, wherein at least about 80% of a dose of PTH in the microprotrusion array is in the end portions of each microprotrusion in the plurality of microprotrusions.

12. The method of claim 1, wherein the steps of applying and inserting occur at an abdominal skin site.

13. The method of claim 1, whereby the method is effective to achieve an elimination half-life that is less than about 45 minutes.

14. The method of claim 1, whereby the method is effective to achieve an elimination half-life that is at least about 20% faster than the elimination half life achieved with the same, or lower dose, of PTH delivered via subcutaneous injection.