Apparatus and method for manufacturing an intracutaneous microneedle array

• US 20020020688A1
• Filed: 09/19/2001
• Published: 02/21/2002
• Est. Priority Date: 06/09/1999
• Status: Active Grant

• Current Assignee: Corium, Inc.
• Original Assignee: The Procter & Gamble Company
• Inventors: Sherman, Faiz Feisal, Gartstein, Vladimir, Owens, Grover David, Yuzhakov, Vadim Vladimirovich
• Granted Patent: US 6,471,903 B2
• Time in Patent Office: Days
• US Class Current: 216/2
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• 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: A61M 37/0015 by using microneedles
• CPC Class Codes: B26F 1/24 Perforating by needles or pins
• CPC Class Codes: B29C 2059/023 Microembossing
• CPC Class Codes: B29C 33/0033 constructed for making articles provided with holes
• CPC Class Codes: B29C 33/42 characterised by the shape of the moulding surface, e.g. ribs or grooves
• CPC Class Codes: B29C 37/0053 Moulding articles characterised by the shape of the surface, e.g. ribs, high polish mould construction therefor B29C33/42; surface shaping of articles B29C59/00; by incorporating filler in or near the surface B29C70/64
• CPC Class Codes: B29C 45/2628 with mould parts forming holes in or through the moulded article, e.g. for bearing cages
• CPC Class Codes: B29C 51/00 Shaping by thermoforming , i.e. shaping sheets or sheet like preforms after heating, e.g. shaping sheets in matched moulds or by deep-drawing; Apparatus therefor blow moulding of tubular preforms B29C49/00, deforming of tubular or hollow preforms B29C67/0014
• CPC Class Codes: B29C 51/082 by shaping between complementary mould parts
• 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 1/00111 Tips, pillars, i.e. raised structures microneedles A61M37/0015
• CPC Class Codes: B81C 2201/036 Hot embossing

Abstract

One embodiment of a microneedle array is constructed of silicon and silicon dioxide compounds using MEMS technology and standard microfabrication techniques to create hollow cylindrical individual microneedles. The resulting array of microneedles is designed to penetrate the stratum corneum and epidermis layers of skin, but not into the dermis. In a second embodiment, an array of hollow (or solid) microneedles are constructed of molded plastic, in which a micro-machining technique is used to fabricate the molds used in a plastic microforming process. Such molds contain a micropillar array and/or microhole array. The manufacturing procedures for creating plastic arrays of microneedles include: “self-molding,” micromolding, microembossing, and microinjection techniques. In the “self-molding” method, a plastic (e.g., polymer) film is placed on a micropillar array, the plastic is then heated, and plastic deformation due to gravitational force causes the plastic film to deform and create the microneedle structure. Using this procedure, only a single mold-half is required. When using the micromolding technique, a similar micropillar array is used along with a second mold-half, which is then closed over the plastic film to form the microneedle structure. The micro-embossing method uses a single mold-half that contains an array of micropillars and conical cut-outs (microholes) which is pressed against a flat surface (which essentially acts as the second mold-half) upon which the plastic film is initially placed. In the microinjection method, a molten plastic substance is injected between two micro-machined molds that contain microhole and micropillar arrays.

Claims

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

(a) providing a bottom mold structure having a substantially horizontal base surface and a plurality of substantially vertical micropillars, said micropillars each having a top surface of a substantially equal height;

(b) placing a planar material on the top surface of said plurality of micropillars;

(c) heating said material to just above its melting temperature, while holding the temperature of said micropillars to a temperature just below the melting temperature of said material;

(d) allowing said material to begin to deform due to a temperature gradient within the planar material, and due to one of gravitational and centrifugal force;

(e) continuing to allow said material to deform until a portion of said deformed material touches said substantially horizontal base surface, at which time substantially all of said material has melted away from the top surface of said plurality of micropillars;

(f) cooling said mold and said material to a temperature below the melting temperature of said material; and

(g) detaching said material from said bottom mold structure, thereby leaving a unitary structure of an array of hollow microneedles.

2. The method as recited in claim 1, further comprising applying one of air pressure and vacuum to assist the deforming of said material.

3. The method as recited in, claim 1, wherein said material comprises a polymer film.

4. The method as recited in claim 1, wherein each of said plurality of micropillars is substantially cylindrical in shape.

5. A method of manufacturing a microneedle array, comprising:

(a) providing a bottom mold structure having a substantially horizontal base surface and a plurality of substantially vertical micropillars, said micropillars each having a top surface of a substantially equal height;

(b) providing a top mold structure having a plurality of microholes;

(c) aligning said bottom mold structure and said top mold structure so that said plurality of micropillars is substantially in alignment with said plurality of microholes;

(d) placing a planar material on the top surface of said plurality of micropillars;

(e) heating said material to above its glass-transition temperature;

(f) pressing said bottom and top mold structures to a predetermined distance from one another to deform said material therebetween;

(g) cooling said mold and said material to a temperature below the melting temperature of said material; and

(h) detaching said material from said top and bottom mold structures, thereby leaving a unitary structure of an array of hollow microneedles.

6. The method as recited in claim 5, wherein said material comprises a polymer film.

7. The method as recited in claim 5, wherein each of said plurality of micropillars is substantially cylindrical in shape, and each of said plurality of microholes is substantially conical in shape.

8. A method of manufacturing a microneedle array, comprising:

(a) providing a top mold structure and bottom mold structure, said top mold structure having a bottommost substantially planar surface, said bottom mold structure having a topmost substantially planar surface, the combination of said top and bottom mold structures defining a plurality of microholes and a plurality of micropillars that are located within said microholes, said micropillars each extending a substantially equal length which causes said micropillars to extend beyond said bottommost surface, said micropillars being configured so as to prevent said bottommost surface from contacting said topmost surface when said top and bottom mold structures are closed, thereby creating a gap between the bottommost surface of said top mold structure and the topmost surface of said bottom mold structure;

(b) heating, in a separate container, a moldable material to above its melting temperature;

(c) injecting, when said top and bottom mold structures are closed, said moldable material into said gap between the bottom surface of said top mold structure and the top surface of said bottom mold structure;

(d) cooling said mold and said material to a temperature below the melting temperature of said material; and

(e) opening said top and bottom mold structures, and detaching said material from said top and bottom mold structures, thereby leaving a unitary structure of an array of hollow microneedles.

9. The method as recited in claim 8, wherein said material comprises a polymer.

10. The method as recited in claim 8, wherein each of said plurality of micropillars is substantially cylindrical in shape, and each of said plurality of microholes is substantially conical in shape, and said individual micropillars and microholes being concentric.

11. A method of manufacturing a microneedle array, comprising:

(a) providing a bottom mold structure having a substantially planar base surface;

(b) providing a top mold structure having a bottom substantially planar surface, and a plurality of microholes in said bottom surface;

(c) placing a planar material on the top surface of said bottom mold structure;

(d) heating said material to above its glass-transition temperature;

(e) pressing together said bottom and top mold structures until the bottom planar surface of said top mold structure and the planar base surface of said bottom mold surface are separated by a predetermined distance, thereby deforming said material therebetween;

(f) cooling said mold and said material to a temperature below the melting temperature of said material; and

(g) detaching said material from said top and bottom mold structures, thereby leaving a unitary structure of an array of microneedles.

12. The method as recited in claim 11, wherein said material comprises a polymer film.

13. The method as recited in claim 11, wherein said microneedles are solid.

14. The method as recited in claim 13, wherein each of said plurality of microholes is substantially conical in shape.

15. The method as recited in claim 11, further comprising:

providing a plurality of micropillars each extending a substantially equal length, said micropillars being located within said microholes, said micropillars extending beyond said bottom planar surface; and

pressing together said bottom and top mold structures until said plurality of micropillars come into contact with top surface of said bottom mold structure, thereby deforming said material therebetween.

16. The method as recited in claim 15, wherein said microneedles are hollow.

17. The method as recited in claim 15, wherein each of said plurality of micropillars is substantially cylindrical in shape, and each of said plurality of microholes is substantially conical in shape, and said individual micropillars and microholes being concentric.

19. The method as recited in claim 18, wherein said wafer comprises double side polish 100-type silicon, and has an oxide layer on its top surface.

20. The method as recited in claim 18, wherein each of said plurality of hollow microneedles is substantially cylindrical in shape, and each of said through holes is annular.

21. The method as recited in claim 18, wherein the process of creating a plurality of annular oxide patterns on the top surface of said wafer comprises:

oxidizing the top surface of said wafer, then performing a pattern oxide operation.

22. The method as recited in claim 18, wherein the process of forming a plurality of indentations in the bottom surface comprises:

performing a low pressure vapor nitride deposition operation to form a silicon nitride layer on the bottom surfaces of said wafer, then performing a pattern bottom operation and an etching operation on the bottom surface of said wafer.

23. The method as recited in claim 18, wherein the process of forming a plurality of needle-like projections in the top surface of said wafer comprises:

performing a low pressure vapor nitride deposition operation to form a silicon nitride layer on the top surface of said wafer, then performing a pattern top nitride operation and a deep reactive ion etch operation.

24. The method as recited in claim 18, wherein the process of forming a plurality of through holes in said plurality of needle-like projections comprises:

removing said top silicon nitride layer, and performing a deep reactive ion etch operation.

18. A method of manufacturing a microneedle array, comprising:

(a) providing a semiconductor wafer;

(b) creating a plurality of annular oxide patterns on the top surface of said wafer;

(c) forming a plurality of indentations in the bottom surface;

(d) forming, by etching away material, a plurality of needle-like projections in the top surface of said wafer, said needle-like projections having locations that are aligned with said indentations; and

(e) forming a plurality of through holes in said plurality of needle-like projections, thereby creating an array of hollow microneedles.