Applicators for microneedles

• US 20080183144A1
• Filed: 01/22/2008
• Published: 07/31/2008
• Est. Priority Date: 01/22/2007
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: Corium International, Inc.
• Inventors: Singh, Parminder, Trautman, Joseph C., Worsham, Robert Wade, Klemm, Steven Richard, Bowers, Danny Lee, Bayramov, Danir F.
• Granted Patent: US 8,821,446 B2
• Time in Patent Office: Days
• US Class Current: 604/272
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles

Abstract

A microneedle applicator is provided which has two roughly concentric portions which may be, for example, a solid disk and an annulus surrounding it. On the skin-facing side of the inner portion of the applicator a microneedle array is located. The outer portion of the applicator is placed against the skin, contacting it at a zone. The microneedle array is then pressed towards the skin.

Claims

1. An applicator for a microprojection array, the applicator comprising an inner and outer portion wherein

(a) the microprojection array attaches to or is integral with the inner portion,

(b) the outer portion comprises a contact zone for contacting skin, and

(c) the shape of the applicator may be varied between a first and second stable configurations.

2. The applicator of claim 1, wherein at least a portion of the contact zone is coated with adhesive for adhering to skin.

3. The applicator of claim 1, wherein the inner and outer portions meet at a closed curve.

4. The applicator of claim 3, wherein the curve at which the inner and outer portions meet is approximately circular.

5. The applicator of claim 1, wherein the inner and outer portions are integral with each other.

6. The applicator of claim 1, wherein the change of shape of the applicator comprises an inversion of the outer portion in a plane.

7. The applicator of claim 1, wherein the applicator may be switched between the first and second configurations with manual pressure.

8. The applicator of claim 1, wherein the applicator may be switched between the first and second configurations at least 2 times without damage to the applicator.

9. The applicator of claim 7, wherein the applicator may be switched between the first and second configurations at least 10 times without damage to the applicator.

10. The applicator of claim 1, wherein the microprojection array comprises a plurality of microneedles.

11. The applicator of claim 1, wherein the microprojection array is designed for a single use.

12. The applicator of claim 1, wherein the inner portion or the outer portion or both comprise a polymer selected from the group consisting of polyethylene terephthalate, glycol-modified polyethylene terephthalate, high-impact polystyrene, polycarbonate, polyvinylchloride, polyurethane, polyethylene, polypropylene, silicone rubber, polymethyl methacrylate, polyvinyl alcohol, acrylonitrile-butadiene-styrene, ethylene vinyl acetate, phenylene oxide, polysulfones, or natural rubber.

13. The applicator of claim 1, wherein the inner portion or the outer portion or both comprise a metal.

14. The applicator of claim 1, wherein the transition from one stable configuration to another pushes the microprojection array into the skin.

15. The applicator of claim 14, wherein the microprojection array impacts the skin with a velocity between about 0.01 and 20 meters/sec.

16. The applicator of claim 15, wherein the microprojection array impacts the skin with a velocity between 0.1 and 10 meters/sec.

17. The applicator of claim 1, further comprising a reservoir for a liquid comprising a drug substance and one or more channels for transporting the liquid from the reservoir to the vicinity of the microprojection array.

18. The applicator of claim 1, further comprising a reservoir for solid drug substance and diffusion path for the solid drug substance to diffuse from the reservoir to the microprojection array.

19. The applicator of claim 1, wherein the skin surrounding the microprojection array is pulled up above the level of the microprojection array when the applicator is in the second stable configuration.

20. The applicator of claim 1, wherein a threshold force is required to transition the device from the first stable configuration to the second stable configuration.

21. The applicator of claim 20, wherein the threshold force is between about 0.1 and about 20 lbf.

22. The applicator of claim 20, wherein the threshold force is between about 1 lbf and about 10 lbf.

23. The applicator of claim 1, further comprising a further structure capable of mating with or attaching to the inner portion, wherein pressure in a direction approximately perpendicular to the inner portion which is applied to the further structure is spread more uniformly to the inner and outer portions of the applicator than pressure applied directly to the inner portion.

24. The applicator of claim 23, wherein the further structure has approximately the shape of the inner and outer portions in the first stable configuration.

25. The applicator of claim 23, wherein as the applicator approaches the second stable configuration, the outer portion of the applicator presses against the further structure and is held in position by the further structure.

26. The applicator of claim 1, wherein the inner portion of the applicator is approximately flat and the outer portion is approximately frustoconical.

27. The applicator of claim 1, wherein the inner portion has a shape which projects towards the skin when the applicator is used.

28. The applicator of claim 1, wherein the portion of the applicator not including the microprojections is symmetric under rotation about an axis which is approximately parallel to a microprojection.

29. The applicator of claim 1, wherein the outer perimeter of the contact zone does not significantly expand when the applicator shifts between the first and second stable configurations.

30. The applicator of claim 2, wherein the adhesive is in the form of a film and the applicator contacts more of the film upon changing from the first stable configuration to the second stable configuration.

32. A method for testing for a condition in a patient, comprising:

(a) applying a microprojection array to the skin of the patient employing an applicator as described in claim 1,

(b) collecting biological fluid using microchannels created in the skin by the microprojection array,

(c) detecting the presence of one or more biomarkers in the collected biological fluid.

33. A method for administering an active agent, comprising:

(a) applying a microprojection array to the skin of the patient employing an applicator as described in claim 1,

(b) causing the active agent to pass through skin using microprojections created in the skin by the microprojection array.

34. The method of claim 33, wherein the microprojection array is used for one of bolus, sustained, pulsatile, or continuous drug delivery.

35. The method of claim 33, wherein the microprojection array is used for one of acute, intermittent, or chronic drug delivery.

36. The method of claim 33, wherein the active agent has a molecular weight exceeding 500 Daltons.

37. The method of claim 36, wherein the active agent has a molecular weight exceeding 1000 Daltons.

38. The method of claim 33, further comprising the step of applying an adhesive to skin and then contacting the applicator to the adhesive applied to skin.

39. The method of claim 33, wherein an adhesive is applied to the outer portion of the applicator prior to applying the microprojection array to the skin.

31. An applicator for a microprojection array comprising an inner and outer portion wherein

(a) the microprojection array attaches to or is integral with the inner portion,

(b) the outer portion has a contact zone designed for contacting skin,

(c) the inner and outer portions are integral with each other, and

(d) the relative positions of the inner and outer portions may be varied between a first and second configurations, wherein the applicator tensions the skin when it is in the second configuration.

40. A method for delivering a drug substance, comprising:

(a) covering an area of skin with a laminate comprising at least one polymer chosen from the group consisting of polyimide-1, vinyl pyrrolidone, polyvinyl pyrrolidone, lauryl methacrylate copolymers, albumin, hydroxypropyl methylcellulose, copolyvidone, acrylates, cyanoacrylates, nitrocellulose, pyroxylin, polyethylene terephthalate, high density polyethylene, ethylene vinyl acetate, polyurethanes, and polyphenylmethylsiloxane, and

(b) pressing a microprojection array through at least a portion of the area of skin covered by the laminate, so that the microprojections of the array penetrate the skin creating channels in the skin through which drug substance may pass.

41. A microneedle array comprising:

(a) microneedles pointing in approximately the same direction and

(b) elongated members each at an angle to the microneedles,

wherein the elongated members or attachments between them are sufficiently flexible to allow the microneedles to move in a direction approximately perpendicular to the axes of the needles, and wherein pressure on the array in a direction approximately aligned with that of the axes of the microneedles is transmitted at least in part to the microneedles, so that pressure in that direction can cause microneedles to move apart as they are inserted into skin.

42. An applicator for a microprojection array comprising an inner and outer portion wherein

(a) the microprojection array attaches to or is integral with the inner portion,

(b) the outer portion comprises a contact zone designed for contacting skin, and

(c) the relative positions of the inner and outer portions may be varied between a first stable configuration and a second configuration in which the applicator remains for a substantial period of time before returning to the first stable configuration.

43. The applicator of claim 42, wherein the applicator comprises a laminate at least one of whose components contributes energy to the transition of the applicator to the inverted configuration.

44. The applicator of claim 42, wherein the applicator comprises an inner portion containing an adhesive which holds the device in a second configuration for a substantial period of time before returning to the first stable configuration.

45. A method for facilitating or maintaining penetration by a microprojection array by pulling upward the skin surrounding the location of the microprojection array.

46. The method of claim 45, wherein the pulling is carried out by means of (a) an applicator to which the microprojection array is attached and (b) an adhesive film between a portion of the applicator and skin.