Microarray for delivery of therapeutic agent, methods of use, and methods of making

• US 9,962,534 B2
• Filed: 03/14/2014
• Issued: 05/08/2018
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: Corium International, Inc.
• Inventors: Chen, Guohua, Ding, Zhongli, Ghartey-Tagoe, Esi, Shastry, Ashutosh, Worsham, Robert Wade, Singh, Parminder
• Primary Examiner(s): Yuan, Dah-Wei D
• Assistant Examiner(s): BOWMAN, ANDREW J
• Application Number:
  US14/214,377
• Publication Number:
  US 20140272101A1
• Time in Patent Office: 1,516 Days
• Field of Search: 604506, 264319, 313503
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles

Abstract

Devices and methods for using and manufacturing microstructure arrays are described.

Claims

1. A method of making an array of microstructures comprising:

(a) dissolving or suspending at least one therapeutic agent and at least one polymer in one or more solvents to form a polymer matrix solution or suspension;

(b) dispensing the polymer matrix solution or suspension on a mold having an array of microstructure cavities;

(c) filling the microstructure cavities in the mold with the polymer matrix solution or suspension;

(d) removing excess polymer matrix solution or suspension on the mold surface;

(e) a first drying step comprising drying the polymer matrix solution or suspension at a temperature of about 5-50°

C. in a chamber having a partial pressure of water of about 0.01 mTorr to about 203 Torr or a relative humidity of about 50-95% for about 5-30 minutes;

(f) a second drying step comprising drying the polymer matrix solution or suspension at about 5-50°

C. for about 30 minutes in an oven without controlled partial pressure of water or relative humidity to form an array of microstructures; and

(g) drying the microstructures under vacuum at about 5-50°

C.

2. The method of claim 1, wherein step (a) comprises:

(i) dissolving or suspending the at least one therapeutic agent in a first solvent to form a therapeutic agent solution or suspension;

(ii) dissolving the at least one polymer in a second solvent to form a polymer solution or suspension; and

(iii) mixing the therapeutic agent solution or suspension and the polymer solution or suspension to form the polymer matrix solution or suspension.

3. The method of claim 1, wherein the chamber uses convection, conduction, or radiation for drying.

4. The method of any previous claim, further comprising:

dispensing a basement or backing layer on the mold surface; and

drying the basement or backing layer.

5. The method of claim 4, wherein drying the basement or backing layer comprises drying in an oven at about 5-50°

C.

6. The method of claim 4, wherein drying the basement or backing layer comprises drying in a compressed dry air box with controlled air flow prior to drying in an oven.

7. The method of any one of claim 4, further comprising:

affixing the basement or backing layer to a substrate.

8. The method of claim 7, wherein the substrate is selected from a pressure sensitive adhesive and a UV cured adhesive.

9. The method of claim 7, further comprising:

affixing the basement or backing layer to the substrate using a nonwoven or porous film double coated with adhesive.

10. The method of claim 1, further comprising:

demolding the microstructure array.

11. The method of claim 4, further comprising demolding the microstructure array after drying the basement or backing layer.

12. The method of claim 1, further comprising:

applying a wetting agent to the mold prior to step (b).

13. The method of claim 12, wherein the wetting agent is selected from calcium carbonate, ethyl acetate, a silicone fluid, oxygen plasma, or a silicone polyether surfactant.

14. The method of claim 1, wherein step (c) comprises pressurization of at least about 10 psi above atmospheric.

15. The method of claim 1, wherein step (c) uses soluble gases.

16. The method of claim 15, wherein the soluble gas is selected from CO₂ and CH₄.

17. The method of claim 1, wherein step (a) further comprises dissolving at least one of a sugar, a surfactant, or an antioxidant in the one or more solvents.

18. The method of claim 1, further comprising dissolving a sugar in the polymer matrix solution or suspension after step (a).

19. The method of claim 17, wherein the sugar is selected from sorbitol, sucrose, trehalose, fructose, or dextrose.

20. The method of claim 17, wherein the surfactant is selected from Polysorbate 20 or Polysorbate 80.

21. The method of claim 17, wherein the antioxidant is selected from methionine, cysteine, D-alpha tocopherol acetate, EDTA, or vitamin E.

22. The method of claim 1, wherein step (a) comprises dissolving about 10-40% by weight of the at least one polymer in the one or more solvents.

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

24. The method of claim 1, wherein the suspension is a liquid in liquid suspension or a solid in liquid suspension.

25. The method of claim 2, wherein at least one of the first or second solvents is water.