Method of molding for microneedle arrays

• US 20070191761A1
• Filed: 02/22/2005
• Published: 08/16/2007
• Est. Priority Date: 02/23/2004
• Status: Abandoned Application

• Current Assignee: 3M Innovative Properties Company (3M Company)
• Original Assignee: 3M Innovative Properties Company (3M Company)
• Inventors: Frederickson, Franklyn, Carter, Chad, Boone, Mary
• Application Number:
  US10/590,210
• Publication Number:
  US 20070191761A1
• Time in Patent Office: Days
• US Class Current: 604/46
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61B 2017/00526 Methods of manufacturing
• CPC Class Codes: A61B 2017/00893 pharmaceutically effective
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: B29C 2045/0094 injection moulding of small-sized articles, e.g. microarticles, ultra thin articles
• CPC Class Codes: B29C 2045/7393 alternately heating and cooling
• CPC Class Codes: B29C 33/3842 Manufacturing moulds, e.g. shaping the mould surface by machining
• CPC Class Codes: B29C 33/3857 by making impressions of one or more parts of models, e.g. shaped articles and including possible subsequent assembly of the parts
• CPC Class Codes: B29C 33/42 characterised by the shape of the moulding surface, e.g. ribs or grooves
• CPC Class Codes: B29C 45/2669 with means for removing excess material, e.g. with overflow cavities B29C45/1711 takes precedence
• CPC Class Codes: B29C 45/37 Mould cavity walls , i.e. the inner surface forming the mould cavity, e.g. linings
• CPC Class Codes: B29C 45/372 provided with means for marking or patterning, e.g. numbering articles
• CPC Class Codes: B29C 45/561 Injection-compression moulding
• CPC Class Codes: B29C 45/73 of the mould B29C45/2642 and B29C45/2737 take precedence
• CPC Class Codes: B29L 2031/753 Medical equipment; Accessories therefor bloodbags, medical bags B29L2031/7148; artificial eyes B29L2011/0008
• CPC Class Codes: B29L 2031/7544 Injection needles, syringes
• CPC Class Codes: B29L 2031/756 Microarticles, nanoarticles
• CPC Class Codes: B81B 2201/055 Microneedles
• CPC Class Codes: B81C 99/0085 using moulds and master templates, e.g. for hot-embossing
• CPC Class Codes: C25D 1/10 : Moulds; Masks; Masterforms

Abstract

A method of manufacturing a moldable microneedle array (54) is described comprising providing a negative mold insert (44) characterized by a negative image of microneedle topography wherein at least one negative image of a microneedle is characterized by an aspect ratio of between about 2 to 1 and about 5 to 1. The negative mold insert (44) is used to define a structured surface of a negative mold cavity (42). Molten plastic material is injected into the heated negative mold cavity. The molten plastic material is subsequently cooled and detached from the mold insert to provide a molded microneedle array (54). One manner of using microneedle arrays of the present invention is in methods involving the penetration of skin to deliver medicaments or other substances and/or extract blood or tissue through the skin.

Claims

1. A method of manufacturing a molded microneedle array comprising:

providing a negative mold insert characterized by a negative image of microneedle topography wherein at least one negative image of a microneedle is characterized by an aspect ratio of between about 2 to 1 and about 5 to 1;

transferring the negative mold insert into an injection molding apparatus, wherein the negative mold insert is exposed and defines a structured surface of a negative mold cavity;

heating the negative mold cavity to a temperature above the softening temperature of a moldable plastic material;

heating the moldable plastic material to at least the molten temperature of the moldable plastic material in a chamber separate from the negative mold cavity;

injecting the molten plastic material into the heated negative mold cavity,

allowing the molten plastic material to fill at least about 90 percent of the volume of the negative indentations defined by the negative mold insert;

cooling the molten plastic material to a temperature below the softening temperature of the moldable plastic material; and

detaching the molded microneedle array from the negative mold insert.

3. A method according to claim 1,

wherein the negative mold insert is formed by:

providing a positive mold master member characterized by microneedle topography wherein at least one microneedle is characterized by an aspect ratio of between about 2 to 1 and about 5 to 1;

electroforming a negative mold insert around the positive mold master; and

detaching the negative mold insert from the positive mold master member.

4. A method according to claim 3, wherein the positive mold master member comprises copper.

5. A method according to claim 1, wherein the negative mold insert is fabricated by nickel electroforming.

6. A method according to claim 3, wherein the microneedle topography of the positive mold master member is prepared by diamond turning.

7. A method according to claim 1, wherein the microneedle array comprises,a plurality of microneedles each having a flat tip comprising a surface area measured in a plane aligned with the base of about 20 square micrometers or more and 100 square micrometers or less.

8. A method according to claim 1, wherein the microneedle array is formed as part of a larger array, wherein at least a portion of the larger array comprises a non-patterned substrate.

9. A method according to claim 8, wherein the non-patterned substrate has an area of more than about 0.10 square inch (0.65 cm²) to less than about 1 square inch (6.5 cm ²).

10. A method according to claim 1, wherein the microneedle array comprises a plurality of molded microneedles having a height greater than about 90 percent of the corresponding height of the microneedle topography in the negative mold insert.

12. A method according to claim 1, wherein the moldable plastic material comprises a material selected from the group consisting of polycarbonate, polystyrene, polyethylene, polypropylene, and blends thereof.

16. A method according to claim 1, wherein the microneedle array comprises a plurality of microneedles having a pyramidal shape.

17. A method according to claim 1, wherein the molten plastic material is injected into the heated negative mold cavity with a velocity of less than 2.0 in/sec (5.08 cm/sec).

18. A method according to claim 17, wherein after injection of the molten material, it is held at a packed pressure of more than about 6000 psi (40.8 Mpa).

29. A product manufactured according to the process of claim 1.

30. A product according to claim 29, wherein the product is a drug delivery device.

2. A method of manufacturing a molded microneedle array comprising:

providing a negative mold insert characterized by a negative image of microneedle topography wherein at least one negative image of a microneedle is characterized by an aspect ratio of between about 2 to 1 and about 5 to 1;

transferring the negative mold insert into an injection molding apparatus, wherein the negative mold insert is exposed and defines a structured surface of a negative mold cavity;

heating the negative mold cavity to a temperature of more than about 10 degrees centigrade above the softening temperature of a moldable plastic material;

heating the moldable plastic material to at least the molten temperature of the moldable plastic material in a chamber separate from the negative mold cavity;

injecting the molten plastic material into the heated negative mold cavity,

allowing the molten plastic material to fill at least about 90 percent of the volume of the negative indentations defined by the negative mold insert;

cooling the molten plastic material to a temperature at least below the softening temperature of the moldable plastic material; and

detaching the molded microneedle array from the negative mold insert.

15. A method according to claim 2, wherein the negative mold cavity is heated to a temperature of more than about 30 degrees centigrade above the softening temperature of the moldable plastic material.

11. (canceled)

13-14. -14. (canceled)

19. A method of manufacturing a negative mold insert used for preparing molded microneedle arrays comprising:

providing a positive mold master member characterized by microneedle topography wherein at least one microneedle is characterized by an aspect ratio of between about 2 to 1 and about 5 to 1;

electroforming a negative mold insert around the positive mold master; and

detaching the negative mold insert from the positive mold master member.

20. A method according to claim 19, wherein the positive mold master member comprises copper.

21. A method according to claim 19, wherein the negative mold insert is fabricated by nickel electroforming.

23. A method according to claim 19, wherein the positive mold master comprises a plurality of microneedles each having a flat tip comprising a surface area measured in a plane aligned with the base of about 20 square micrometers or more and 100 square micrometers or less.

26. A method of manufacturing a molded microneedle array comprising:

providing a negative mold insert prepared according to claim 19,

transferring the negative mold insert into a molding apparatus, wherein the negative mold insert is exposed and defines a structured surface of a negative mold cavity;

providing a heated plastic material into the negative mold cavity,

allowing the heated plastic material to fill at least about 90 percent of the volume of the negative indentations defined by the negative mold insert;

cooling the plastic material to a temperature at least below the softening temperature of the plastic material; and

detaching the molded microneedle array from the negative mold insert.

27. A method according to claim 26, wherein the molding apparatus is an injection molding apparatus.

28. A method according to claim 26, wherein the negative mold cavity is heated to a temperature of more than about 10 degrees centigraigrade above the softening temperature of the plastic material prior to providing the heated plastic material to the negative mold.

22. (canceled)

24-25. -25. (canceled)