Solvent-cast microprotrusion arrays containing active ingredient

• US 9,452,280 B2
• Filed: 07/10/2013
• Issued: 09/27/2016
• Est. Priority Date: 04/16/2007
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: Corium International, Inc.
• Inventors: Singh, Parminder, Worsham, Robert Wade, Trautman, Joseph C., Bayramov, Danir, Bowers, Danny Lee, Klemm, Andy, Klemm, Steven Richard, Chen, Guohua
• Primary Examiner(s): YI, STELLA KIM
• Application Number:
  US13/939,123
• Publication Number:
  US 20130292868A1
• Time in Patent Office: 1,175 Days
• Field of Search: 264/334, 264/50, 264/674, 264/676, 264/212
• US Class Current: 1/1
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 38/385 Serum albumin
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2202/0007 introduced into the body
• CPC Class Codes: A61M 2202/07 Proteins
• CPC Class Codes: A61M 2202/30 Vaccines
• CPC Class Codes: A61M 2207/00 Methods of manufacture, assembly or production
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 5/3298 Needles arranged in parallel

Abstract

In an aspect of the invention, an array of microprotrusions is formed by providing a mold with cavities corresponding to the negative of the microprotrusions, casting atop the mold a first solution comprising a biocompatible material and a solvent, removing the solvent, casting a second solution atop the first cast solution, removing the solvent from the second solution, and demolding the resulting array from the mold. The first solution preferably contains an active ingredient.

Claims

1. A method of making a microstructure array, comprising:

dispensing onto a mold having an array of microstructure cavities a formulation comprising a polymer, a therapeutic agent and a solvent, said formulation being dispensed in an amount sufficient to at least partially fill the microstructure cavities, said dispensing being carried out in presence of a gas having a solubility in the formulation or the mold that is greater than the solubility of air in the formulation or the mold;

drying the formulation; and

demolding from the mold a microstructure array.

2. The method of claim 1, wherein the gas is carbon dioxide.

3. The method of claim 1, wherein the gas is more soluble in the formulation or the mold than oxygen.

4. The method of claim 1, further comprising:

dispensing a second formulation on the mold surface to form a second layer; and

drying the second layer.

5. The method of claim 4, further comprising:

affixing a backing to the second layer.

6. The method of claim 5, wherein the backing comprises polyethylene terephthalate.

7. The method of claim 1, wherein said dispensing is carried out at atmospheric pressure.

8. The method of claim 1, wherein said dispensing is carried out at a pressure higher than atmospheric pressure.

9. The method of claim 1, wherein the therapeutic agent is selected from a drug, a small molecule, a peptide or protein, or a vaccine.

10. The method of claim 1, further comprising:

prior to said dispensing, dissolving or suspending the therapeutic agent and the polymer in a solvent to form the formulation.

11. The method of claim 10, wherein the solvent is water.

12. The method of claim 10, wherein the formulation further comprises at least one sugar.

13. The method of claim 12, wherein the sugar is selected from the group consisting of sorbitol, sucrose, trehalose, fructose, and dextrose.

14. The method of claim 10, wherein the formulation further comprises a surfactant.

15. The method of claim 14, wherein the surfactant is polysorbate.

16. The method of claim 10, wherein the formulation further comprises an antioxidant.

17. The method of claim 16, wherein the antioxidant is selected from the group consisting of methionine, cysteine, D-alpha tocopherol acetate, EDTA, and vitamin E.

18. The method of claim 1, wherein prior to said dispensing, the mold is subjected to a surface treatment over at least a portion of its surface.

19. The method of claim 1, wherein said drying is performed under vacuum.