Microneedle array applicators and systems

Abstract

Various embodiments of a microneedle array applicator (12) are disclosed. The applicator includes an applicator body (16) and an opening (22) extending therethrough, an actuator (26) configured to slidably engage the applicator body between the applicator's unactuated and activated configurations, and a plunger (32) disposed at least partially within the opening in the applicator body. The plunger includes a latch (36) configured to engage with a slot (40) disposed in the upper portion (18) of the applicator body to retain the plunger at least partially within the opening in the applicator body when the applicator is in the unactuated configuration. The applicator further includes a stored energy device (42). The applicator is operated from the unactuated configuration to the activated configuration by axially compressing the actuator and applicator body, causing the actuator to bias the latch inward, disengaging the latch from the slot in the applicator body and releasing the plunger.

Description

[Technical Field]

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 422,965, filed November 5, 2022, the entire disclosure of which is incorporated herein by reference. [Background technology]

[0002] Although transdermal and topical drug delivery can be used for therapeutic treatments, the number of molecules that can be effectively delivered using these routes may be limited by the barrier properties of the skin. The primary barrier to the transport of molecules through the skin is the stratum corneum (the outermost layer of the skin).

[0003] Different skin treatment techniques have been proposed to increase the permeability or porosity of outermost layers, such as the stratum corneum, to enhance drug delivery through or into these layers. The stratum corneum is a composite structure of dense, keratinized cellular remnants separated by lipid domains. It is composed of keratinocytes, the majority of which are corneocytes that lose their nuclei to become epidermal cells. These dead cells make up the stratum corneum, which is only approximately 10–30 microns thick and protects the body against invasion by exogenous substances and the outward movement of endogenous fluids and dissolved molecules. Various skin treatment methods include the use of microneedling, laser ablation, RF ablation, thermal ablation, sonophoresis, iontophoresis, or a combination of these treatment methods.

[0004] Devices containing arrays of relatively small structures, sometimes called microneedles or micropins, have been described for delivering therapeutic agents and other substances through the skin and other surfaces. These devices can be pressed against the skin to perforate the stratum corneum in a manner that allows therapeutic agents and other substances to pass sequentially or simultaneously through the layer and into the underlying tissue. The microneedles of these devices perforate the stratum corneum upon contact, creating multiple tiny slits that serve as pathways through which molecules of the active ingredient can be delivered into the body. To deliver the active ingredient, the microneedle device can be equipped with a reservoir for temporarily holding the active ingredient in liquid form before delivering it through the stratum corneum. In some configurations, the microneedles can be hollow to provide a liquid flow path directly from the reservoir through the microneedles to deliver the therapeutic agent through the skin. In an alternative configuration, the active ingredient can be coated onto a microneedle array and delivered directly through the skin after perforating the stratum corneum.

[0005] Applicators can be used to deploy microneedle arrays and patches. Microneedle arrays and patches are generally used only once and then discarded, while applicators can be disposable or reusable. Summary of the Invention

[0006] Generally, the present disclosure provides various embodiments of a system including a microneedle array and a microneedle array applicator that can be used to apply the array to a user's skin. The applicator can include an applicator body and an actuator configured to be slidably engaged with the applicator body. A plunger can be disposed at least partially within an opening disposed through the applicator body. The applicator can be configured to be operated from an unactuated configuration to an activated configuration by axially compressing the actuator and applicator body along one axis. Such compression disengages the plunger from the applicator body. When disengaged from the applicator body, the plunger guides the microneedle array through a lower surface of the applicator body and onto the user's skin. In one or more embodiments, a user can operate the applicator from the unactuated configuration to the activated configuration in a continuous motion without the applicator resting or being held in the activated configuration prior to activation.

[0007] In one aspect, the present disclosure provides a microneedle array applicator. The applicator includes an applicator body having an upper portion, a lower portion, and an opening extending through the upper and lower portions along an axis, the lower portion configured to be positioned adjacent to a user's skin; an actuator configured to slidably engage the applicator body between the unactuated and activated configurations of the applicator; and a plunger at least partially disposed within the opening of the applicator body. The plunger includes a base and a latch extending from an inner surface of the base. The latch is configured to engage a slot disposed in the upper portion of the applicator body when the applicator is in the unactuated configuration to retain the plunger at least partially within the opening of the applicator body. The applicator further includes a stored energy device disposed between the base of the plunger and the inner surface of the actuator. The stored energy device is configured to be compressed and biased as the applicator is operated from the unactuated configuration to the activated configuration. The applicator is configured such that the applicator is operated from an unactuated configuration to an actuated configuration by axially compressing the actuator and applicator body, whereby operating the applicator from the unactuated configuration to the actuated configuration causes the actuator to bias the latch inward, disengaging the latch from the slot in the applicator body and releasing the plunger.

[0008] In another aspect, the present disclosure provides a system including a microneedle array and a microneedle array applicator. The applicator includes an applicator body including an upper portion, a lower portion, and an opening extending through the upper and lower portions along an axis, the lower portion configured to be positioned adjacent to the skin of a user; an actuator configured to slidably engage the applicator body between an unactuated configuration and an activated configuration of the applicator; and a plunger at least partially disposed within the opening of the applicator body. The plunger includes a base and a latch extending from an inner surface of the base. The latch is configured to engage a slot disposed in the upper portion of the applicator body when the applicator is in the unactuated configuration to retain the plunger at least partially within the opening of the applicator body. The applicator further includes a stored energy device disposed between the base of the plunger and the inner surface of the actuator. The stored energy device is configured to be compressed and biased as the applicator is operated from the unactuated configuration to the activated configuration. The applicator is configured such that axial compression of the actuator and applicator body operates the applicator from an unactuated configuration to an actuated configuration, and operating the applicator from the unactuated configuration to the actuated configuration causes the actuator to deflect the latch inward, disengaging the latch from the slot in the applicator body and releasing the plunger.

[0009] In another aspect, the present disclosure provides a method including the steps of: positioning a microneedle array within an opening in an applicator body of an applicator, the opening extending along an axis through upper and lower portions of the applicator body; the applicator further including an actuator slidably engaged with the applicator body and a plunger at least partially disposed within the opening of the applicator body. The method further includes the steps of positioning the applicator adjacent to a user's skin; and manipulating the applicator from an unactuated configuration to an activated configuration. Manipulating the applicator from the unactuated configuration to an activated configuration includes axially compressing the actuator and applicator body of the applicator along the axis. A stored energy device disposed between the base of the plunger and an inner surface of the actuator is compressed and energized when the applicator is operated from the unactuated configuration to the activated configuration. The actuator further biases a latch extending from the inner surface of the plunger base inward, disengaging the latch from a slot disposed in the upper portion of the applicator body and releasing the plunger.

[0010] All headings provided herein are for the convenience of the reader and should not be used to limit the meaning of any text that follows the heading, unless otherwise specified.

[0011] The term "comprises" and variations thereof do not have a limiting meaning where they appear in the description and claims. Such terms are to be understood as implying the inclusion of a step or element or group of steps or elements and not the exclusion of any other step or element or group of steps or elements.

[0012] In this application, the terms "a," "an," and "the" are not intended to refer to a singular entity only, but are intended to include general classes of which specific examples can be used for illustration. The terms "a," "an," and "the" are used interchangeably with the term "at least one." The phrases "at least one of" and "comprise at least one of," followed by a list, refer to any one of the items in the list and any combination of two or more items in the list.

[0013] As used herein, the term "or" is generally used in its ordinary sense, including "and / or," unless the context clearly dictates otherwise.

[0014] The term "and / or" means one or all of the listed elements or a combination of any two or more of the listed elements.

[0015] As used herein, the term "about" in connection with a measured quantity means that variation of the measured quantity that would be expected by a person of ordinary skill in the art making the measurement and exercising a level of care appropriate to the purpose of the measurement and the precision of the measuring equipment used. As used herein, "up to" a number (e.g., up to 50) is inclusive of that number (e.g., 50).

[0016] Similarly, herein the recitations of numerical ranges by endpoints include all numbers subsumed within that range, as well as endpoints (eg, 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).

[0017] These and other aspects of the present disclosure will become apparent from the following detailed description. In no event, however, should the foregoing summary be construed as a limitation on the claimed subject matter, which subject matter is defined solely by the appended claims, as may be amended during prosecution.

[0018] Throughout the specification, reference will be made to the accompanying drawings, wherein like reference numerals represent like elements and in which: [Brief explanation of the drawings]

[0019] [Figure 1] FIG. 1 is a schematic perspective view of one embodiment of a system including a microneedle array and a microneedle array applicator. [Figure 2] FIG. 2 is a schematic exploded view of the system of FIG. [Figure 3] FIG. 3 is a schematic cross-sectional view of the system of FIG. 1 with the applicator of the system in an unactuated configuration. [Figure 4] FIG. 4 is a schematic cross-sectional view of the system of FIG. 1 with the applicator being activated from an unactivated configuration to an activated configuration. [Figure 5] FIG. 5 is a schematic cross-sectional view of the system of FIG. 1 with the applicator in an activated configuration. [Figure 6] FIG. 6 is a schematic top plan view of the applicator body of the applicator of FIG. [Figure 7] 7 is a schematic bottom plan view of the applicator body of the applicator of FIG. 1. FIG. [Figure 8] FIG. 8 is a schematic bottom plan view of the applicator of FIG. [Figure 9] FIG. 9 is a perspective view of a microneedle array of the system of FIG. [Figure 10] FIG. 10 is a schematic cross-sectional view of a portion of the microneedle array of FIG. [Figure 11] 11 is a schematic perspective view of a stored energy device of the applicator of FIG. 1; FIG. [Figure 12]FIG. 12 is a flow diagram of one technique for using the system of FIG. DETAILED DESCRIPTION OF THE INVENTION

[0020] Generally, the present disclosure provides various embodiments of a system including a microneedle array and a microneedle array applicator that can be used to apply the array to a user's skin. The applicator can include an applicator body and an actuator configured to be slidably engaged with the applicator body. A plunger can be disposed at least partially within an opening disposed through the applicator body. The applicator can be configured to be operated from an unactuated configuration to an activated configuration by axially compressing the actuator and applicator body along one axis. Such compression disengages the plunger from the applicator body. When disengaged from the applicator body, the plunger guides the microneedle array through a lower surface of the applicator body and onto the user's skin. In one or more embodiments, a user can operate the applicator from the unactuated configuration to the activated configuration in a continuous motion without the applicator resting or being held in the activated configuration prior to activation.

[0021] Before describing any embodiments of the present disclosure in detail, it should be understood that these embodiments are not limited in their application to the structural details and component arrangements set forth in the specification or illustrated in the drawings. The embodiments may be practiced or embodied in various ways. Likewise, it should be understood that the phraseology and terminology used herein are for purposes of description and should not be considered limiting. Furthermore, terms such as "front," "rear," "top," "bottom," "upward," "downward," "under," and the like, are used only to describe elements in relation to one another and are not intended in any way to describe a particular orientation of these elements, to indicate or imply a required or necessary orientation of such elements, or to dictate how the elements described herein are to be used, assembled, displayed, or positioned during use.

[0022] In discussing the microneedle array applicators of the present disclosure, the term "downward" and variations thereof are sometimes used to describe the direction in which the microneedles are pressed into the skin, and "upward" is used to describe the opposite direction. However, those skilled in the art will understand that microneedles can be used to be pressed into the skin at an angle relative to the direction of Earth's gravity, and even in a direction opposite to the direction of Earth's gravity, and that these terms are merely used for simplicity and clarity to describe the relative directions.

[0023] The term "transdermally" and its variants are generally used to mean any type of delivery of an active ingredient across any part of the skin. That is, "transdermal" generally refers to systemic delivery (i.e., when the active ingredient is delivered into the skin, the active ingredient is transported across or substantially through the dermis so as to be delivered into the bloodstream), as well as intradermal delivery (i.e., when the active ingredient is partially transported through the dermis, for example, across the outer layer of the skin (stratum corneum)). That is, as used herein, transdermal delivery includes delivery of an active ingredient that is transported across at least a portion of the skin, rather than simply being applied topically to the outer layer of the skin.

[0024] The present disclosure generally relates to applicators and techniques for applying a microneedle device comprising an array of microneedles to the skin (or biological membrane) to treat the skin (i.e., to create small holes or perforations or micropores in the skin) and / or to deliver active agents to the skin.

[0025] 1-11 show various views of one embodiment of a microneedle array applicator system 10 and elements or components of such a system. System 10 includes an applicator 12 and a microneedle array 14 (FIG. 2). As can be seen in FIG. 3, applicator 12 includes an applicator body 16 having an upper portion 18, a lower portion 20, and an opening 22 extending through the upper and lower portions along an axis 2. Lower portion 20 is configured to be placed adjacent to a user's skin 4. Applicator 12 further includes an actuator 26 configured to slidably engage applicator body 16 between the applicator's unactuated configuration (FIG. 3) and activated configuration (FIG. 5). Applicator 12 further includes a plunger 32 at least partially disposed within opening 22 of applicator body 16. Plunger 32 includes a base 34 and a latch 36 extending from an inner surface 38 of the base. Latch 36 is configured to engage a slot 40 disposed in upper portion 18 of applicator body 16 when applicator 12 is in the unactuated configuration to retain the plunger at least partially within applicator body opening 22. Applicator 12 further includes a stored energy device 42 disposed between base 34 of plunger 32 and inner surface 30 of actuator 26. Stored energy device 42 is configured to be compressed and biased as applicator 12 is manipulated from the unactuated configuration to the actuated configuration.

[0026] The applicator 12 is configured such that the applicator 12 is operated from an unactuated configuration to an actuated configuration by axially compressing the actuator 26 and the applicator body 16. Further operating the applicator 12 from the unactuated configuration to the actuated configuration causes the actuator to bias the latch 36 inward, disengaging the latch from the slot 40 in the applicator body 16 and releasing the plunger 32.

[0027] The applicator body 16 of the applicator 12 can comprise any suitable material, such as at least one inorganic (e.g., metal) or organic (e.g., polymer) material. Furthermore, the applicator body 16 can have any suitable shape and any suitable dimensions. For example, the applicator body 16 can have a uniform cross-sectional shape in a plane perpendicular to the axis 2. In one or more embodiments, the applicator body 16 can have a cross-sectional shape that varies along the axis 2. Furthermore, the upper portion 18 of the applicator body 16 can have a cross-sectional shape that is different from the cross-sectional shape of the lower portion 20.

[0028] The upper portion 18 can have an oval cross-sectional shape in a plane perpendicular to the axis 2. As shown in FIG. 2, the upper portion 18 includes a cylindrical shape extending from the lower portion 20 of the applicator body 16. Further, the lower portion 20 can have an oval cross-sectional shape in a plane perpendicular to the axis 2. In one or more embodiments, the lower portion 20 of the applicator body 16 includes a rounded triangular shape ( FIG. 7 ) in a plane perpendicular to the axis 2.

[0029] Applicator body 16 may include a recess 46 (FIG. 5) disposed within lower portion 20 of the applicator body and configured to accommodate a lower portion 48 of actuator 26. Additionally, ridges or ribs 52 may be disposed on actuator 26 configured to engage applicator body 16 when applicator 12 is in the actuated configuration (FIG. 5), where the ribs act as stops to movement of the actuator when the actuator and applicator body are compressed.

[0030] The applicator body 16 may further include one or more ribs 54 (FIGS. 2 and 7) disposed on an outer surface 56 of the upper portion 18 of the applicator body that extend in a direction substantially parallel to the axis 2. Each rib 54 is configured to slidably engage with a slot 58 (FIG. 8) disposed in the inner surface 30 of the actuator 26 to prevent rotation of the actuator about the axis 2 when the actuator is manipulated axially relative to the applicator body 16. In one or more embodiments, one or more ribs 54 may be disposed on the inner surface 30 of the actuator 26, and one or more slots 58 may be disposed in the outer surface 56 of the upper portion 18 of the applicator body 16 that slidably engage with each rib.

[0031] The applicator body 16 may further include one or more superior tabs 66 ( FIG. 3 ), which may take any suitable shape and may be located within any suitable portion of the upper portion 18 of the applicator body. As shown in FIG. 3 , the superior tabs 66 may be located within the upper portion 18 of the applicator body 16 and extend in a direction substantially parallel to axis 2. The applicator body 16 may further include one or more apertures 96 located within the upper portion 18 proximate the superior tabs 66, which are adapted to receive actuator arms 70 extending from the inner surface 30 of the actuator 26. The actuator arms 70, which may define a portion of the inner surface 30 of the actuator, are configured to engage with the superior tabs 66 of the applicator body 16 to retain the actuator 26 to the applicator body such that the applicator body and the actuator remain coupled after assembly. During such assembly, the applicator body 16 is slidable within the actuator 26 such that the actuator arms 70 are inserted within the applicator body 16 and engage with the superior tabs 66. In one or more embodiments, the actuator arm 70 includes a notch 68 ( FIG. 3 ) that engages with the upper tab 66 on the applicator body 16 to retain the actuator 26 on the applicator body when the applicator is in the unactuated configuration. The actuator arm 70 can further include a sloped portion 69 configured to engage with the upper tab 66 on the applicator body 16 to retain the applicator in the actuated configuration ( FIG. 5 ) and prevent a user from resetting the applicator 12 to the unactuated configuration.

[0032] The slots 40 of the applicator body 16 can be positioned within the upper portion 18 of the applicator body. In one or more embodiments, the slots 40 can be positioned within the upper surface 62 of the upper portion 18 of the applicator body 16. The slots 40 can take any suitable shape and have any suitable dimensions. As shown in FIG. 7 , the slots 40 include prongs 78 each configured to receive the latch 36 of the plunger 32 and retain the plunger 32 at least partially within the opening 22 of the applicator body 16 when the applicator is in the unactuated configuration ( FIG. 3 ). The applicator body 16 can include any suitable number of slots 40. The slots 40 can be positioned within any suitable portion of the upper surface 62 of the upper portion 18 of the applicator body 16. In one or more embodiments, the upper surface 62 of the upper portion 18 can include a recessed portion 74 ( FIG. 6 ) within which the slots 40 can be positioned. The recessed portion 74 can take any suitable shape and have any suitable dimensions. In one or more embodiments, recessed portion 74 can have a depth selected such that latch 36 of plunger 32 does not extend beyond upper surface 62 of applicator body 16 when the latch is disposed through slot 40. Additionally, recessed portion 74 can be shaped to accommodate extension portion 76 extending from inner surface 30 of actuator 26 when applicator 12 is in the actuated configuration, as shown in FIG.

[0033] An opening 22 in the applicator body 16 extends through the upper and lower portions 18, 20 along the axis 2. Such opening 22 may have any suitable cross-sectional shape in a plane perpendicular to the axis 2. In one or more embodiments, a plunger guide 60 may extend from an upper surface 62 of the applicator body 16 into the opening 22. An aperture 64 may be disposed within the plunger guide 60 along the axis. Such aperture 64 may have any suitable shape. The aperture 64 terminates at the upper surface 62 of the applicator body 16 and is coupled to the slot 40. The aperture 64 is configured to receive one or more latches 36 of the plunger 32. The plunger guide 60 and aperture 64 can be configured to guide the latch 36 of the plunger 32 through the slot 40 when the applicator 12 is assembled, and downward toward the lower surface 24 of the lower portion 20 of the applicator body 16 when the applicator 12 is operated from the unactuated configuration to the actuated configuration.

[0034] The applicator body 16 further includes a lower surface 24 configured to be positioned adjacent to the user's skin 4. The lower surface 24 may take any suitable shape. Additionally, the lower surface 24 may include a textured surface or one or more protrusions configured to prevent the applicator 12 from sliding over the skin 4 while the applicator is being manipulated from the unactuated position to the actuated position, as described further below.

[0035] Slidably engaged with applicator body 16 is actuator 26. Actuator 26 can comprise any suitable material, such as the same materials described herein with respect to applicator body 16. In one or more embodiments, actuator 26 can be manufactured using the same material as applicator body 16. In one or more embodiments, actuator 26 can comprise a different material than the material of applicator body 16.

[0036] The actuator 26 can take any suitable shape and have any suitable dimensions. In one or more embodiments, the actuator outer surface 72 can include an ergonomic shape configured to be gripped by a user's hand. As shown in FIGS. 3-5 , the actuator 26 is configured to slidably engage the applicator body 16 by sliding over the applicator body such that one or more portions of the actuator inner surface 30 come into contact with one or more portions of the applicator body outer surface 56. In one or more embodiments, the actuator 26 is configured to slide within the applicator body 16 such that one or more portions of the actuator outer surface 72 come into contact with one or more portions of the applicator body. In other words, the actuator 26 can be configured to slide within the applicator body 16.

[0037] In one or more embodiments, actuator 26 is configured to slidably engage at least upper portion 18 of applicator body 16 along axis 2. In one or more embodiments, actuator 26 can be configured to slidably engage upper portion 18 and lower portion 20 of applicator body 16. Actuator 26 can slidably engage applicator body 16 along axis 2 between an unactuated configuration ( FIG. 3 ) and an actuated configuration ( FIG. 5 ) of applicator 12, as further described herein.

[0038] The actuator 26 can be configured to deflect the latch 36 inward, disengaging the latch from the slot 40 in the applicator body 16 and releasing the plunger 32. The inner surface 30 of the actuator 26 can include any suitable element or component configurable to deflect the latch 36. For example, the inner surface 30 can include a cavity 28 disposed within the inner surface along the axis 2. The cavity 28 of the actuator 26 can be disposed within an extension 76 that defines a portion of the inner surface 30 of the actuator 26. The cavity 28 can have any suitable shape and any suitable dimensions. In one or more embodiments, the cavity 28 can be frusto-conical in shape. In one or more embodiments, the cavity 28 is configured to deflect the latch 36 of the plunger 32 inward, disengaging the latch from the slot 40 in the applicator body 16 and releasing the plunger. In one or more embodiments, the stored energy device 42 drives the plunger 32 toward the lower surface 24 of the lower portion 20 of the applicator body 16 .

[0039] The inner surface 30 of the actuator 26 may further include actuator arms 70. The actuator arms 70 may take any suitable shape and have any suitable dimensions. The actuator 26 may include any suitable number of arms 70. As shown in FIG. 8 , the actuator 26 includes three actuator arms 70 extending from the inner surface 30 of the actuator and helping to define the inner surface. At least one actuator arm 70 includes a notch 68 that engages with an upper tab 66 on the applicator body 16 to retain the actuator on the applicator body when the applicator 12 is in the unactuated configuration. At least one actuator arm 70 further includes a ramped portion 69 configured to engage with the upper tab 66 on the applicator body 16 to retain the applicator 12 in the actuated configuration and prevent the user from further manipulating the applicator into the unactuated configuration. The actuator arms 70 are also configured to engage with the stored energy device 42 and compress the stored energy device between the actuator 26 and the plunger 32, as described further herein. In one or more embodiments, each actuator arm 70 may include a contact surface 50 configured to contact the stored energy device 42 .

[0040] Disposed at least partially within the opening 22 of the applicator body 16 is a plunger 32. The plunger 32 includes a base 34 and one or more latches 36 extending from an inner surface 38 of the base. The latches 36 are configured to engage slots 40 disposed in an upper portion of the applicator body 16 to retain the plunger 32 at least partially within the opening 22 of the applicator body when the applicator 12 is in an unactuated configuration.

[0041] The plunger 32 can comprise any suitable material, such as the same materials described herein with respect to the applicator body 16. In one or more embodiments, the plunger 32 can comprise a material different from the material of at least one of the applicator body 16 or the actuator 26. The plunger 32 can similarly have any suitable shape and any suitable dimensions. Furthermore, the base 34 can similarly have any suitable shape and any suitable dimensions. The base 34 includes an inner surface 38 and an outer surface 82. The outer surface 82 can be configured to contact the microneedle array 14 and actuate the array onto the skin 4 when the actuator 26 is actuated from the unactuated configuration to the actuated configuration. The outer surface 82 can be positioned in any suitable relationship relative to the microneedle array 14. In one or more embodiments, the outer surface 82 can be positioned a selected distance from the microneedle array 14 when the actuator is in the unactuated configuration. In one or more embodiments, the outer surface 82 can be in contact with the array 14 when the actuator is in the unactuated configuration.

[0042] Generally, the plunger 32 is at least partially disposed within the opening 22 of the applicator body 16. In one or more embodiments, the plunger 32 is disposed completely or entirely within the opening 22 of the applicator body 16 when the applicator is in the unactuated configuration. In one or more embodiments, the plunger 32 can be disposed completely within the opening 22 of the applicator body 16 when the applicator is in the actuated configuration. In one or more embodiments, at least a portion of the plunger 32 can be disposed outside the opening 22 of the applicator body 16 when the applicator is in the actuated configuration. As shown in FIG. 5 , at least a portion of the base 34 of the plunger 32 (e.g., outer surface 82) can extend through the lower surface 24 of the lower portion 20 of the applicator body 16 when the applicator 12 is in the actuated configuration.

[0043] Extending from the inner surface 38 of the plunger 32 are one or more latches 36. The plunger 32 may include any suitable number of latches 36. As shown in FIG. 2 , the plunger 32 includes a first latch 36-1, a second latch 36-2, and a third latch 36-3 (collectively, latches 36) extending from the inner surface 38 of the base 34. Each latch 36 may have any suitable shape and any suitable dimensions. Additionally, each latch 36 may include a sloped portion 44 disposed proximate a distal end 84 of the latch 36. The sloped portion 44 may similarly have any suitable shape and any suitable dimensions. In one or more embodiments, the latch 36 may be positioned on the applicator body 16, and the slot 40 may be positioned within the plunger 32.

[0044] As referred to herein, the latches 36 are configured to engage with slots 40 disposed in the upper surface 62 of the applicator body 16. The latches 36 are further configured to retain the plunger 32 at least partially within the opening in the applicator body 16 when the applicator 12 is in the unactuated configuration. The first, second, and third latches 36 are each configured to engage with slots 40 disposed in the upper surface 62 of the upper portion 18 of the applicator body 16 to retain the plunger at least partially within the opening 22 in the applicator body when the applicator 12 is in the unactuated configuration. Furthermore, operating the actuator 26 from the unactuated configuration to the actuated configuration causes the actuator to bias each of the first, second, and third latches 36 inwardly, disengaging such latch from the slots 40 and releasing the plunger 32. FIG. 4 is a schematic cross-sectional view of the applicator 12 while being operated from the unactuated configuration to the actuated configuration. 4, the cavities 28 engage the latches 36 as the actuator 26 is compressed in the applicator body 16. As the actuator 26 continues to be compressed, the cavities 28 bias the angled portions 44 of each of the first, second, and third latches 36 inward, causing the latches to disengage from the slots and advance through the apertures 64 in the plunger guide 60.

[0045] In one or more embodiments, the plunger 32 may also include an arm 86 ( FIG. 3 ) extending from the base 34. The arm 86 may be configured to engage one or more protrusions 98 ( FIG. 5 ) disposed within the applicator body 16 to retain the plunger to the applicator body when the applicator 12 is in the actuated configuration, as shown in FIG. 5 . In other words, the arm 86 retains the plunger 32 at least partially within the opening 22 of the applicator body 16 after the latch 36 is released from engagement with the slot 40 in the upper portion 18 of the applicator body. The latch 36 of the plunger 32 may likewise be configured to engage a surface 88 ( FIG. 5 ) disposed within the plunger guide aperture 64 to maintain the coupling of the plunger and the applicator body 16 after the applicator is manipulated into the actuated configuration.

[0046] The stored energy device 42 of the applicator 12 is disposed between the base 34 of the plunger 32 and the inner surface 30 of the actuator 26, as shown in FIG. 3 . In one or more embodiments, the stored energy device 42 can be disposed on the plunger guide 60. The stored energy device 42 is configured to be compressed and biased as the applicator 12 is operated from the unactuated configuration ( FIG. 3 ) to the actuated configuration ( FIG. 5 ). In one or more embodiments, the stored energy device 42 can also be configured to be slightly compressed when the applicator is in the unactuated configuration ( FIG. 3 ) such that the device and plunger 32 remain stable in the unactuated configuration. The stored energy device 42 can include any suitable device configured to store energy until the applicator 12 is operated to the actuated configuration. When the applicator 12 is in the actuated configuration, the stored energy device 42 is configured to transfer stored energy to the plunger 32 by driving the plunger against the lower surface 24 of the lower portion 20 of the applicator body 16. The stored energy device 42 may include one or more individual springs configured in either a series or parallel configuration. In one or more embodiments, the stored energy device 42 includes at least one of a conical coil spring, a coil spring, or an extension spring. In one or more embodiments, the stored energy device 42 includes a wave spring, as shown in FIG. 11 . Generally, a wave spring is a compression spring made of flat wire with multiple “waves” 88 per turn. In one or more embodiments, one or more shims 90 may be coupled to at least a top end 92 or a bottom end 94 of the stored energy device 42, as shown in FIG. 11 . Such shims 90 may provide flat surfaces at each end 92, 94 of the device 42 to interact with the inner surface 30 of the actuator 26 and the inner surface 38 of the plunger 32. In one or more embodiments, wave springs may offer advantages over traditional coil springs because, when fully compressed, they have a lower cross-sectional profile, which may result in a lower overall device height.A further advantage of wave springs over conventional springs is that they provide a more evenly distributed force around their diameter, since there are actually many springs in parallel.

[0047] The stored energy device 42 can be compressed and biased using any suitable technique. In one or more embodiments, one or more actuator arms 70 extending from the inner surface 30 of the actuator 26 can each be positioned within an aperture 96 ( FIG. 6 ) located in the upper surface 62 of the upper portion 18 of the applicator body 16. As the actuator 26 is manipulated from an unactuated configuration to an actuated configuration, each actuator arm 70 presses against the stored energy device 42, compressing it against (e.g., against) the inner surface 38 of the base 34 of the plunger 32. Because the plunger 32 is held in place by the latch 36, the stored energy device 42 continues to be compressed and biased until the latch is released from the slot 40 of the applicator body 16 by the actuator 26 and the plunger is driven by the stored energy device toward the lower surface 24 of the lower portion 18 of the applicator body 16.

[0048] Disposed within the opening 22 of the lower portion 20 of the applicator body 16 is a microneedle array 14, which may include any suitable microneedle device or patch. For example, FIG. 9 is a schematic perspective view of one embodiment of a microneedle array 14. The microneedle array 14, which may also be referred to herein as a "microneedle device" or "patch," may include microneedles 100 and any support structure or substrate 102 used to support the microneedles or to couple the microneedles to other structures or components. The microneedle array 14 can be retained within the opening 22 of the applicator body 16 using any suitable technique. In one or more embodiments, the microneedle array 14 can be retained within the opening by one or more protrusions 98 ( FIG. 3 ) extending from the lower portion 20 of the applicator body 16 to the opening 22 until the plunger 32 guides the array through the lower surface 24 of the applicator body lower portion 20 when the applicator is operated into the activated configuration.

[0049] As mentioned herein, in one or more embodiments, an active ingredient or agent (e.g., a drug) can be delivered via the microneedles 100 (e.g., via solid microneedles, dissolving microneedles, or hollow microneedles, as described below). Pharmaceutically active agents (also referred to as "drugs") that can be incorporated into the applicators of the present disclosure are those that can exert a local or systemic effect when administered to the skin. Some examples include buprenorphine, clonidine, diclofenac, estradiol, granisetron, isosorbide dinitrate, levonorgestrel, lidocaine, methylphenidate, nicotine, nitroglycerin, oxybutynin, rivastigmine, rotigotine, scopolamine, selegiline, testosterone, tulobuterol, and fentanyl, which are commercially available in transdermal devices. Other examples include anti-inflammatory drugs, both steroidal (e.g., hydrocortisone, prednisolone, triamcinolone) and non-steroidal (e.g., naproxen, piroxicam, etc.); bacteriostatic drugs (e.g., chlorhexidine, hexylresorcinol); antibacterial drugs (e.g., penicillins, e.g., penicillin V; cephalosporins, e.g., cephalexin, erythromycin, tetracycline, gentamicin, sulfathiazole, nitrofurantoin, and quinolones, e.g., norfloxacin, flumequine, and ibafloxacin); antiprotozoal drugs (e.g., metronidazole); antifungal drugs (e.g., nystatin); coronary angiotensin inhibitors (e.g., thiazol-2 ... Vasodilators; calcium channel blockers (e.g., nifedipine, diltiazem); bronchodilators (e.g., theophylline, pirbuterol, salmeterol, isoproterenol); enzyme inhibitors, such as collagenase inhibitors, protease inhibitors, acetylcholinesterase inhibitors (e.g., donepezil), elastase inhibitors, lipoxygenase inhibitors (e.g., A64077), and angiotensin-converting enzyme inhibitors (e.g., captopril, lisinopril); other antihypertensives (e.g., prolanolol); leukotriene antagonists (e.g., ICI204, 219); antiulcer drugs, such as H2 antagonists; steroid hormones (e.g., progesterone);Antiviral and / or immunomodulatory agents (e.g., 1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine, 1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine, N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]methanesulfonamide, and acyclovir); local anesthetics (e.g., benzocaine, propofol, tetracaine, prilocaine); cardiac inotropes (e.g., digitalis, digoxin) antitussives (e.g., codeine, dextromethorphan); antihistamines (e.g., diphenhydramine, chlorpheniramine, terfenadine); narcotic analgesics (e.g., morphine, fentanyl citrate, sufentanil, hydromorphone hydrochloride); peptide hormones (e.g., human or animal growth hormone, LHRH, parathyroid hormone); cardioactive products, e.g., atriopeptides; antidiabetic drugs (e.g., insulin, exanatide); enzymes (e.g., antiplaque enzymes, lysozyme, dextromethorphan); xtranase); antiemetics; anticonvulsants (e.g., carbamazepine); immunosuppressants (e.g., cyclosporine); psychotherapeutic drugs (e.g., diazepam); sedatives (e.g., phenobarbital); anticoagulants (e.g., heparin, enoxaparin sodium); analgesics (e.g., acetaminophen); antimigraine medications (e.g., ergotamine, melatonin, sumatriptan, zolmitriptan); antiarrhythmics (e.g., flecainide); antiemetics (e.g., metaclopromide, ondansetron, granisetron hydrochloride); anti These include cancer drugs (e.g., methotrexate); nervous system drugs, such as anti-anxiety drugs; hemostatic drugs; anti-obesity drugs; dopamine agonists (e.g., apomorphine); GnRH agonists (e.g., leuprolide, goserelin, nafarelin); ovulation-stimulating hormones (e.g., hCG, hMG, urofollitropin); interferons (e.g., interferon-alpha, interferon-beta, interferon-gamma, pegylated interferon-alpha), and the like, as well as pharmaceutically acceptable salts and esters thereof. The amount of drug that constitutes a therapeutically effective amount can be readily determined by those skilled in the art, taking into account the specific drug, the specific carrier, and the desired therapeutic effect.

[0050] In one or more embodiments, peptide therapeutics (natural, synthetic, or recombinant) can be delivered via the microneedles 100 (e.g., via solid, dissolving, or hollow microneedles, as described below). Examples of peptide therapeutics that can be incorporated into the applicators of the present disclosure include parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), calcitonin, lysozyme, insulin, insulin secretagogue analogs, glatiramer acetate, goserelin acetate, somatostatin, octreotide, leuprolide, vasopressin, desmopressin, thymosin alpha-1, atrial natriuretic peptide (ANP), endorphins, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), erythropoietin (EPO), bone morphogenetic protein (BMP), epidermal growth factor (EFG), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), growth hormone-releasing hormone (GH-R) and growth hormone-releasing hormone (GH-R). peptide therapeutics, including but not limited to: steroid hormone (GHRH), donase alfa, tissue plasminogen activator (tPA), urokinase, ANP clearance inhibitors, luteinizing hormone-releasing hormone (LHRH), melanocyte-stimulating hormone (alpha & beta MSH), pituitary hormone (hGH), adrenocorticotropic hormone (ACTH), human chorionic gonadotropin (hCG), streptokinase, interleukins (e.g., IL-2, IL-4, IL-10, IL-12, IL-15, IL-18), protein C, protein S, angiotensin, angiogenin, endothelin, pentigetide, brain natriuretic peptide (BNP), neuropeptide Y, islet amyloid polypeptide (IAPP), vasoactive intestinal peptide (VIP), hirudin, glucagon, oxytocin, and derivatives of any of the foregoing peptide therapeutics.

[0051] In one or more embodiments, drugs with large molecular weights may be delivered transdermally. Increasing the molecular weight of a drug typically results in decreased unassisted transdermal delivery. Examples of such large molecules include proteins, peptides, nucleotide sequences, monoclonal antibodies, vaccines, polysaccharides, e.g., heparin, and antibiotics such as ceftriaxone. Examples of suitable vaccines include therapeutic cancer vaccines, anthrax vaccines, influenza vaccines, Lyme disease vaccines, rabies vaccines, measles vaccines, mumps vaccines, chickenpox vaccines, smallpox vaccines, hepatitis vaccines, hepatitis A vaccines, hepatitis B vaccines, hepatitis C vaccines, pertussis vaccines, rubella vaccines, diphtheria vaccines, encephalitis vaccines, Japanese encephalitis vaccines, respiratory syncytial virus vaccines, yellow fever vaccines, recombinant protein vaccines, DNA vaccines, polio vaccines, herpes vaccines, human papillomavirus vaccines, pneumococcal vaccines, meningitis vaccines, pertussis vaccines, tetanus vaccines, typhoid vaccines, cholera vaccines, tuberculosis vaccines, severe acute respiratory syndrome (SARS) vaccines, HSV-1 vaccines, HSV-2 vaccines, HIV vaccines, and combinations thereof. Thus, the term "vaccine" includes, but is not limited to, antigens in the form of proteins, polysaccharides, oligosaccharides, or attenuated or killed viruses. Additional examples of suitable vaccines and vaccine adjuvants are described in US Patent Application Publication No. 2004 / 0049150 (Dalton et al.), the entire disclosure of which is incorporated herein by reference.

[0052] In another embodiment, small molecule drugs that are otherwise difficult or impossible to deliver via passive transdermal delivery may be used. Examples of such molecules include salt forms; ionic molecules such as bisphosphonates, including sodium alendronate or sodium pamidronate; and molecules with physicochemical properties that are not conducive to passive transdermal delivery.

[0053] Microneedles 100 useful for practicing the present disclosure can have a variety of configurations and features, such as those described in the following patents and patent applications, the entire disclosures of which are incorporated herein by reference: One embodiment of the microneedle 100 includes the structure disclosed in U.S. Patent Application Publication No. 2005 / 0261631 (Clarke et al.), which describes a microneedle having a tapered, truncated shape and a controlled aspect ratio; Another embodiment of the microneedle includes the structure disclosed in U.S. Patent No. 6,091,975 (Daddona et al.), which describes blade-like microprojections for piercing the skin; Yet another embodiment of the microneedle includes the structure disclosed in U.S. Patent No. 6,312,612 (Sherman et al.), which describes a tapered structure having a hollow central channel; Yet another embodiment of the microneedle includes the structure disclosed in U.S. Patent No. 6,379,324 (Gartstein et al.), which describes a hollow microneedle having at least one longitudinal blade on the top surface of the tip of the microneedle. Further embodiments of the microneedles include the structures disclosed in U.S. Patent Application Publication Nos. 2012 / 0123387 (Gonzalez et al.) and 2011 / 0213335 (Burton et al.), both of which describe hollow microneedles. Further embodiments of the microneedles include the structures disclosed in U.S. Patent Application Publication Nos. 6,558,361 (Yeshurun) and 7,648,484 (Yeshurun ​​et al.), both of which describe hollow microneedle arrays and methods of making the same.

[0054] Various embodiments of microneedles that can be used in the microneedle arrays of the present disclosure are described in PCT Publication No. WO 2012 / 074576 (Duan et al.), which describes liquid crystal polymer (LCP) microneedles; and PCT Publication No. WO 2012 / 122162 (Zhang et al.), which describes a variety of different types and compositions of microneedles that can be used in the microneedles of the present disclosure.

[0055] In one or more embodiments, the microneedle material can be (or include) silicon, glass, or a metal such as stainless steel, titanium, or a nickel-titanium alloy. In one or more embodiments, the microneedle material can be (or include) a polymeric material, preferably a medical-grade polymeric material. Exemplary types of medical-grade polymeric materials include polycarbonate, liquid crystal polymer (LCP), polyetheretherketone (PEEK), cyclic olefin copolymer (COC), and polybutylene terephthalate (PBT). Preferred types of medical-grade polymeric materials include polycarbonate and LCP.

[0056] In one or more embodiments, the microneedle material can be (or include) a biodegradable polymer material, preferably a medical-grade biodegradable polymer material. Exemplary types of medical-grade biodegradable materials include polylactic acid (PLA), polyglycolic acid (PGA), PGA and PLA copolymers, and polyester-amide polymers (PEA).

[0057] In one or more embodiments, the microneedles can be prepared from a dissolvable, degradable, or disintegrable material, referred to herein as a "dissolvable microneedle." A dissolvable, degradable, or disintegrable material is any solid material that dissolves, degrades, or disintegrates during use. Specifically, a "dissolvable microneedle" dissolves, degrades, or disintegrates sufficiently in the tissue beneath the stratum corneum to allow the therapeutic agent to be released into the tissue. The therapeutic agent may be coated on or incorporated within the dissolvable microneedle. In one or more embodiments, the dissolvable material is selected from a carbohydrate or sugar. In one or more embodiments, the dissolvable material is polyvinylpyrrolidone (PVP). In one or more embodiments, the dissolvable material is selected from the group consisting of hyaluronic acid, carboxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinyl alcohol, sucrose, glucose, dextran, trehalose, maltodextrin, or a combination thereof.

[0058] In one or more embodiments, the microneedle may be made of (or include) a combination of any two or more of the above materials. For example, the tip of the microneedle may be a dissolvable material while the remainder of the microneedle is a medical grade polymer material.

[0059] A microneedle or microneedles in a microneedle array useful for practicing the present disclosure can have a variety of shapes capable of piercing the stratum corneum. In one or more embodiments, one or more microneedles of the plurality of microneedles can have a square pyramid shape, a triangular pyramid shape, a step-pyramid shape, a cone shape, a microblade shape, or a hypodermic needle shape. In one or more embodiments, one or more microneedles of the plurality of microneedles can have a square pyramid shape. In one or more embodiments, one or more microneedles of the plurality of microneedles can have a triangular pyramid shape. In one or more embodiments, one or more microneedles of the plurality of microneedles can have a step-pyramid shape. In one or more embodiments, one or more microneedles of the plurality of microneedles can have a cone shape. In one or more embodiments, one or more microneedles of the plurality of microneedles can have a microblade shape. In one or more embodiments, one or more microneedles of the plurality of microneedles can have a hypodermic needle shape. The shapes can be symmetrical or asymmetrical. The shape may be truncated (e.g., the plurality of microneedles may have a truncated pyramidal or truncated conical shape). In a preferred embodiment, each of the plurality of microneedles in the microneedle array has a square pyramidal shape.

[0060] In one or more embodiments, the microneedles in the microneedle array are solid microneedles (i.e., the microneedles are solid throughout). In one or more embodiments, the microneedles in the solid microneedle array can have a square pyramid shape, a triangular pyramid shape, a stepped pyramid shape, a cone shape, or a microblade shape. In a preferred embodiment, the microneedles in the solid microneedle array each have a square pyramid shape.

[0061] In one or more embodiments, the plurality of microneedles in the microneedle array are hollow microneedles (i.e., the microneedles contain a hollow bore therethrough). The hollow bore can be from the applicator body of the microneedle to the tip of the microneedle, or the bore can be from the applicator body of the microneedle to a location offset from the tip of the microneedle. In one or more embodiments, one or more microneedles of the plurality of hollow microneedles in the hollow microneedle array can have a conical shape, a cylindrical shape, a square pyramidal shape, a triangular pyramidal shape, or a hypodermic needle shape.

[0062] In one or more embodiments, one or more of the hollow microneedles in the hollow microneedle array can have a conical shape. In one or more embodiments, one or more of the hollow microneedles in the hollow microneedle array can have a cylindrical shape. In one or more embodiments, one or more of the hollow microneedles in the hollow microneedle array can have a square pyramidal shape. In one or more embodiments, one or more of the hollow microneedles in the hollow microneedle array can have a triangular pyramidal shape. In one or more embodiments, one or more of the hollow microneedles in the hollow microneedle array can have a hypodermic needle shape. In a preferred embodiment, each of the hollow microneedles in the hollow microneedle array has the shape of a conventional hypodermic needle.

[0063] 10 shows a portion of a microneedle array 14 including four microneedles 100 positioned on a substrate 102. Each microneedle 100 has a height h, which is the distance from the tip of the microneedle to the body of the microneedle on the substrate 102. Either the height of a single microneedle 100 or the average height of all the microneedles on the microneedle array 14 can be referred to as the microneedle height h. In one or more embodiments, each of the plurality of microneedles 100 (or the average height of all the plurality of microneedles) has a height of about 100 to about 3000 micrometers, in one or more embodiments about 100 to about 1500 micrometers, in one or more embodiments about 100 to about 1200 micrometers, and in one or more embodiments about 100 to about 1000 micrometers. In one or more embodiments, each of the plurality of microneedles 100 (or the average of all of the plurality of microneedles) has a height of about 200 to about 1200 micrometers, about 200 to about 1000 micrometers, about 200 to about 750 micrometers, or about 200 to about 600 micrometers.

[0064] In one or more embodiments using solid microneedles 100, each of the plurality of solid microneedles (or the average of all of the plurality of solid microneedles) has a height of about 100 to about 1500 micrometers, about 100 to about 1200 micrometers, about 200 to about 1000 micrometers, about 200 to about 750 micrometers, about 200 to about 600 micrometers, or about 500 micrometers.

[0065] In one or more embodiments using hollow microneedles, each of the plurality of hollow microneedles (or the average of all of the plurality of hollow microneedles) has a height of about 100 to about 3000 micrometers, about 800 to about 1400 micrometers, or about 500 micrometers.

[0066] A single microneedle 100 or a plurality of microneedles 100 within a microneedle array can also be characterized by their aspect ratio. The aspect ratio of a microneedle is the ratio of the height h of the microneedle to the width w (at the body of the microneedle) (as shown in FIG. 10). The aspect ratio can be expressed as h:w. In one or more embodiments, each of the plurality of microneedles 100 (or the average of all of the plurality of microneedles 100) has an aspect ratio in the range of 2:1 to 5:1. In some of these embodiments, each of the plurality of microneedles 100 (or the average of all of the plurality of microneedles 100) has an aspect ratio of at least 3:1.

[0067] In one or more embodiments, the array of microneedles 100 may comprise a microneedle array 1 cm 2 Each device stores approximately 100 to 1500 microneedles.

[0068] In one or more embodiments, each of the plurality of microneedles in the microneedle array (or the average of all of the plurality of microneedles) can penetrate into the skin to a depth of about 100 to about 400 micrometers or about 100 to about 300 micrometers.

[0069] For all of the above embodiments, it is recognized that the depth of penetration (DOP) of each of the plurality of microneedles (or the average of all of the plurality of microneedles) in the microneedle array should not be the full length of the microneedle itself.

[0070] In one or more embodiments, a microneedle array 14 according to the present disclosure may be in the form of a patch. An example of such an embodiment is shown in FIG. 9. The microneedle array 14 includes a plurality of microneedles 100 disposed on a substrate 102. The microneedle array 14 includes a backing layer 104 and an adhesive layer (not shown) disposed on the backing layer between the backing layer and the microneedle array substrate. The microneedles 100 may be arranged in any desired pattern or randomly distributed across the substrate 102. As shown, the microneedles 100 are arranged in evenly spaced rows. When arranged in rows, the rows can be arranged so that the microneedles 100 are aligned or offset. In one or more embodiments (not shown), the microneedles 100 can be arranged in a polygonal pattern, such as a triangle, square, rectangle, pentagon, hexagon, heptagon, octagon, or trapezoid. In other embodiments (not shown), the microneedles 100 can be arranged in a circular or elliptical pattern.

[0071] In one or more embodiments, the surface area of ​​the substrate 102 covered with microneedles 100 is approximately 0.1 cm 2 ~about 20cm 2 In one or more embodiments, the microneedles 100 can be disposed on substantially the entire surface of the array. In other embodiments (not shown), a portion of the substrate 102 may be free of microneedles (i.e., the portion of the substrate is unstructured). In some of these embodiments, the unstructured surface has an area facing the skin surface that is greater than about 1 percent and less than about 75 percent of the total area of ​​the device surface. In other of these embodiments, the unstructured surface has an area that is greater than about 0.65 cm 2 (0.10 sq. inches) ~ Approx. 6.5 cm 2 (1 square inch) in area.

[0072] For hollow microneedles, a hollow channel or bore extends through the substrate and the microneedle. In one or more embodiments, the bore exits at a channel opening at or near the tip of the hollow microneedle. The channel preferably exits at an opening near the tip of the hollow microneedle. Most preferably, the channel or bore continues along the central axis of the microneedle but exits at a sloped sidewall of the microneedle, similar to a hypodermic needle, to help prevent blockage of the channel by tissue during insertion. In one or more embodiments, the diameter of the channel bore is about 10 to about 200 micrometers. In one or more embodiments of hollow microneedles, the average cross-sectional area of ​​the channel bore is about 75 to about 32,000 micrometers. In one or more embodiments of hollow microneedle arrays, the average separation between adjacent microneedles (measured from tip to tip) is about 0.7 mm to about 20 mm. In one or more embodiments of the hollow microneedle array, the average separation between adjacent microneedles (measured from tip to tip of the microneedles) is greater than about 0.7 mm. In one or more embodiments of the hollow microneedle array, the average separation between adjacent microneedles is less than about 20 mm.

[0073] In one or more embodiments of the solid microneedle array, the average separation between adjacent microneedles (measured from tip to tip of the microneedles) is between about 200 micrometers and about 2000 micrometers. In one or more embodiments of the solid microneedle array, the average separation between adjacent microneedles (measured from tip to tip of the microneedles) is greater than about 200 micrometers. In one or more embodiments of the solid microneedle array, the average separation between adjacent microneedles (measured from tip to tip of the microneedles) is less than about 2000 micrometers.

[0074] Microneedle arrays can be manufactured by any suitable method, such as by injection molding, compression molding, metal injection molding, stamping, photolithography, or extrusion. In one embodiment, hollow microneedle arrays can be made by injection molding a polymer such as medical grade polycarbonate or LCP, followed by laser drilling to form the microneedle channels.

[0075] System 10 can be assembled using any suitable technique. In one or more embodiments, applicator body 16, actuator 26, and plunger 32 of applicator 12 can each be manufactured using any suitable technique, such as molding, injection molding, 3D printing, machining, casting, etc. Actuator 26 can be slid onto applicator body 16 using any suitable technique until upper tab 66 engages notch 68 in actuator arm 70, retaining the applicator body to the actuator. Furthermore, stored energy device 42 can be inserted into opening 22 of applicator body 16 using any suitable technique such that the device is in close proximity to or in contact with actuator arm 70. Plunger 32 can be inserted into opening 22 of applicator body 16 using any suitable technique. In one or more embodiments, latch 36 of plunger 32 can be inserted through aperture 64 of plunger guide 60 until angled portion 44 of the latch is inserted through and retained by slot 40. The microneedle array 14 can be positioned within the applicator body 16 using any suitable technique. In one or more embodiments, the microneedle array 14 can be positioned so that it rests on one or more protrusions 98 that are positioned within the lower portion 20 of the applicator body 16, as shown in FIG. 3. The protrusions 98 can retain the microneedle array 14 within the applicator body 16 until the applicator 12 is manipulated to an actuation configuration, which releases the plunger 32 to disengage the microneedle array from the protrusions and drive the array through the lower surface 24 of the applicator body.

[0076] The system 10 can deliver the microneedle array 14 to the user's skin 4 using any suitable technique. For example, FIG. 12 is a flow diagram of one embodiment of a technique or method 200 utilizing the system 10. Although described with respect to the system 10 of FIGS. 1-11, the technique 200 can be used with any suitable microneedle array system. At 202, the microneedle array 14 can be positioned within the applicator body 16 of the assembled applicator 12 using any suitable technique. In one or more embodiments, the microneedle array 14 is positioned within the applicator body 16 during system manufacture. In one or more embodiments, the array 14 can be positioned within the applicator body 16 by a user. At 204, the lower surface 24 of the lower portion 20 of the applicator body 16 can be placed adjacent to the user's skin 4 or another surface, such as a sterile or sanitized surface. In one or more embodiments, the applicator 12 can be placed on the user's skin 4. At 206, the applicator 12 can be actuated from an unactuated configuration to an actuated configuration using any suitable technique. In one or more embodiments, the applicator 12 can be actuated by axially compressing the actuator 26 and applicator body 16 of the applicator along axis 2. As the actuator 26 and applicator body 16 are compressed, the stored energy device 42 is compressed and biased by the actuator. Furthermore, during actuation, the actuator 26 deflects one or more latches 36 inward, disengaging the latches from slots 40 located in the upper portion 18 of the applicator body 16 and releasing the plunger 32. In one or more embodiments, the stored energy device 42 drives the plunger 32 toward the lower surface 24 of the lower portion 20 of the applicator body 16. By manipulating the applicator 12 from the unactuated configuration to the actuated configuration, the plunger 32 drives the microneedle array 14 from the protrusion 98 on the inner surface of the lower portion 20 of the applicator body 16 toward the user's skin 4, thereby delivering the microneedle array to the skin.The applicator 12 is configured to apply the microneedle array 14 to the skin 4 at an intended rate to achieve a desired array needle penetration depth for efficient drug delivery. In one or more embodiments, a user can manipulate the applicator 12 from the unactuated configuration to the actuated configuration in one continuous motion without pausing or holding the applicator 12 in the unactuated configuration. Optionally, at 208, the applicator 12 can be removed from the skin 4 after the microneedle array 14 has been delivered to the skin 4.

[0077] In one or more embodiments, the user may release the actuator 26 prior to activation of the applicator 12. In such embodiments, the stored energy device 42 returns the applicator to the unactivated configuration, as shown in FIG.

[0078] The present invention is defined in the claims. However, below is provided a non-exhaustive list of non-limiting examples. Any one or more of the features of these examples may be combined with any one or more features of any other example, embodiment, or aspect described herein.

[0079] Example 1: A microneedle array applicator. The applicator includes an applicator body having an upper portion, a lower portion, and an opening extending through the upper and lower portions along an axis, the lower portion configured to be positioned adjacent to the skin of a user; an actuator configured to slidably engage the applicator body between the unactuated and activated configurations of the applicator; and a plunger at least partially disposed within the opening of the applicator body. The plunger includes a base and a latch extending from an inner surface of the base. The latch is configured to engage a slot disposed in the upper portion of the applicator body when the applicator is in the unactuated configuration to retain the plunger at least partially within the opening of the applicator body. The applicator further includes a stored energy device disposed between the base of the plunger and the inner surface of the actuator. The stored energy device is configured to be compressed and biased as the applicator is operated from the unactuated configuration to the activated configuration. The applicator is configured such that axial compression of the actuator and applicator body operates the applicator from an unactuated configuration to an actuated configuration, and operating the applicator from the unactuated configuration to the actuated configuration causes the actuator to deflect the latch inward, disengaging the latch from the slot in the applicator body and releasing the plunger.

[0080] Example 2: The applicator of example 1, wherein the stored energy device comprises a wave spring.

[0081] Example 3: The applicator of example 1, wherein the stored energy device comprises at least one of a conical coil spring, a coil spring, or an extension spring.

[0082] Example 4: The applicator of any one of Examples 1 to 3, wherein the outer surface of the actuator comprises an ergonomic shape.

[0083] Example 5: An applicator described in any one of Examples 1 to 4, wherein the actuator further includes an actuator arm extending from an upper portion of the inner surface of the actuator that engages with an upper tab on the applicator body to retain the actuator on the applicator body, the upper tab extending from a lower portion of the applicator body.

[0084] Example 6: An applicator according to any one of Examples 1 to 5, wherein the actuator includes a cavity disposed within an inner surface of the actuator along the axis, the cavity configured to bias the latch inwardly to disengage the latch from the slot in the applicator body.

[0085] Example 7: An applicator described in any one of Examples 1 to 6, wherein the applicator body further includes a recess disposed in a lower portion of the applicator body configured to accommodate a portion of the lower surface of the actuator.

[0086] Example 8: An applicator according to any one of Examples 1 to 7, wherein the superior portion of the applicator body comprises an elliptical cross-section in a plane perpendicular to the axis.

[0087] Example 9: The applicator of any one of Examples 1 to 7, wherein the upper portion of the applicator body comprises a cylindrical shape.

[0088] Example 10: An applicator according to any one of Examples 1 to 9, wherein the upper portion of the applicator body comprises an elliptical cross-section in a plane perpendicular to the axis.

[0089] Example 11: An applicator described in any one of Examples 1 to 10, wherein the applicator body further includes a rib disposed on an outer surface of the upper portion of the applicator body extending in a direction substantially parallel to the axis, the rib being configured to be slidably received by a slot disposed in an inner surface of the actuator for the purpose of preventing rotation of the actuator about the axis when the actuator is operated along the axis relative to the applicator body.

[0090] Example 12: An applicator according to any one of Examples 1 to 11, wherein the plunger further includes second and third latches extending from an inner surface of the base, each of the second and third latches configured to engage with a slot disposed in an upper surface of the applicator body to retain the plunger at least partially within the opening in the applicator body when the applicator is in an unactuated configuration, and wherein operating the actuator from the unactuated configuration to the actuated configuration causes the actuator to deflect the second and third latches inward, disengaging the second and third latches from the slots in the applicator body and releasing the plunger.

[0091] Example 13: An applicator described in any one of Examples 1 to 12, wherein the plunger further includes an arm extending from the base and configured to engage a protrusion disposed within the opening of the applicator body to retain the plunger on the applicator body.

[0092] Example 14: An applicator described in any one of Examples 1 to 13, wherein the outer surface of the base of the plunger is configured to contact and actuate the microneedle array through a lower surface of the lower portion of the applicator body when the applicator is operated from the unactuated configuration to the actuated configuration.

[0093] Example 15: The applicator of Example 14, wherein an outer surface of the base of the plunger is configured to be in contact with the microneedle array when the applicator is in the unactuated configuration.

[0094] Example 16: A system including a microneedle array and a microneedle array applicator. The applicator includes an applicator body having an upper portion, a lower portion, and an opening extending through the upper and lower portions along an axis, the lower portion configured to be positioned adjacent to the skin of a user; an actuator configured to slidably engage the applicator body between the unactuated configuration and the activated configuration of the applicator; and a plunger at least partially disposed within the opening of the applicator body. The plunger includes a base and a latch extending from an inner surface of the base. The latch is configured to engage a slot disposed in the upper portion of the applicator body when the applicator is in the unactuated configuration to retain the plunger at least partially within the opening of the applicator body. The applicator further includes a stored energy device disposed between the base of the plunger and the inner surface of the actuator. The stored energy device is configured to be compressed and biased as the applicator is operated from the unactuated configuration to the activated configuration. The applicator is configured such that axial compression of the actuator and applicator body operates the applicator from an unactuated configuration to an actuated configuration, and operating the applicator from the unactuated configuration to the actuated configuration causes the actuator to deflect the latch inward, disengaging the latch from the slot in the applicator body and releasing the plunger.

[0095] Example 17: The system described in Example 16, wherein the microneedle array comprises: a plurality of microneedles disposed on a substrate; a backing layer; and an adhesive layer disposed on the backing layer between the backing layer and the substrate of the microneedle array.

[0096] Example 18: The system of any one of Examples 16 to 17, wherein the microneedle array is disposed within the opening of the applicator body of the applicator when the applicator is disposed in the unactuated configuration.

[0097] Example 19: A system described in any one of Examples 16 to 18, wherein the microneedle array is retained within the opening of the applicator by a tab extending from the inner surface of the lower portion of the applicator body.

[0098] Example 20: The system of any one of Examples 16 to 19, wherein the stored energy device of the applicator comprises a wave spring.

[0099] Example 21: The system of any one of Examples 16 to 19, wherein the stored energy device of the applicator includes at least one of a conical coil spring, a coil spring, or an extension spring.

[0100] Example 22: The system of any one of Examples 16 to 21, wherein the outer surface of the actuator of the applicator comprises an ergonomic shape.

[0101] Example 23: A system described in any one of Examples 16 to 22, wherein the actuator of the applicator further includes an actuator arm extending from an upper portion of the inner surface of the actuator that engages with an upper tab of the applicator body of the applicator to retain the actuator on the applicator body, the upper tab extending from a lower portion of the applicator body.

[0102] Example 24: The system of any one of Examples 16 to 23, wherein the actuator includes a cavity disposed within an inner surface of the actuator along the axis, the cavity configured to bias the latch inward to disengage the latch from the slot in the applicator body.

[0103] Example 25: A system described in any one of Examples 16 to 24, wherein the applicator body of the applicator further includes a recess disposed in a lower portion of the applicator body configured to accommodate a portion of the lower surface of the actuator.

[0104] Example 26: The system of any one of Examples 16 to 25, wherein the upper portion of the applicator body comprises an elliptical cross-section in a plane perpendicular to the axis.

[0105] Example 27: The system of any one of Examples 16 to 25, wherein the upper portion of the applicator body comprises a cylindrical shape.

[0106] Example 28: A system according to any one of Examples 16 to 27, wherein the upper portion of the applicator body comprises an elliptical cross-section in a plane perpendicular to the axis.

[0107] Example 29: A system described in any one of Examples 16 to 28, wherein the applicator body of the applicator further includes a rib disposed on an outer surface of the upper portion of the applicator body extending in a direction substantially parallel to the axis, the rib being configured to be slidably received by a slot disposed in an inner surface of the actuator for the purpose of preventing rotation of the actuator about the axis when the actuator is operated along the axis relative to the applicator body.

[0108] Example 30: The system of any one of Examples 16 to 29, wherein the plunger of the applicator further includes second and third latches extending from the inner surface of the base, each of the second and third latches configured to engage with a slot disposed in the upper surface of the applicator body to retain the plunger at least partially within the opening in the applicator body when the applicator is in the unactuated configuration, and wherein operating the actuator from the unactuated configuration to the actuated configuration causes the actuator to deflect the second and third latches inward, disengaging the second and third latches from the slots in the applicator body and releasing the plunger.

[0109] Example 31: A system described in any one of applicators 16 to 30, wherein the plunger of the applicator further includes an arm extending from the base and configured to engage with a protrusion positioned within the opening of the applicator body to retain the plunger on the applicator body.

[0110] Example 32: A system described in any one of Examples 16 to 31, wherein the outer surface of the base of the applicator plunger is configured to contact and actuate the microneedle array through a lower surface of the lower portion of the applicator body when the applicator is operated from the unactuated configuration to the actuated configuration.

[0111] Example 33: The system of Example 32, wherein the outer surface of the plunger is configured to be in contact with the microneedle array when the applicator is in the unactuated configuration.

[0112] Example 34: A method comprising: disposing a microneedle array within an opening in an applicator body of an applicator, the opening extending through upper and lower portions of the applicator body along an axis, the applicator further comprising an actuator slidably engaged with the applicator body and a plunger at least partially disposed within the opening of the applicator body. The method further comprises: disposing the applicator adjacent to a user's skin; and manipulating the applicator from an unactuated configuration to an activated configuration. Manipulating the applicator from the unactuated configuration to an activated configuration comprises axially compressing the actuator and applicator body of the applicator along the axis. A stored energy device disposed between a base of the plunger and an inner surface of the actuator is compressed and energized when the applicator is operated from the unactuated configuration to the activated configuration. The actuator further biases inward a latch extending from the inner surface of the plunger base, disengaging the latch from a slot disposed in the upper portion of the applicator body and releasing the plunger.

[0113] Example 35: The method of Example 34, wherein manipulating the applicator from the unactuated configuration to the actuated configuration causes the plunger to drive the microneedle array toward the user's skin, thereby delivering the microneedle array to the skin.

[0114] Example 36. The method of any one of Examples 34-35, further comprising removing the applicator from adjacent the user's skin after the applicator has been manipulated into the activation configuration.

[0115] Example 37. The method of any one of Examples 34 to 36, wherein the microneedle array comprises a plurality of microneedles disposed on a substrate, a backing layer, and an adhesive layer disposed on the backing layer between the backing layer and the substrate of the microneedle array.

[0116] All references and publications cited herein are expressly incorporated herein by reference in their entirety into this disclosure, except to the extent that they may directly contradict this disclosure. Exemplary embodiments of the present disclosure have been discussed, and possible variations within the scope of the disclosure have been mentioned. These and other variations and modifications will be apparent to those skilled in the art without departing from the scope of the present disclosure, and it should be understood that the present disclosure is not limited to the exemplary embodiments described herein. Accordingly, the present disclosure is limited only by the claims provided below.

Claims

1. In the microneedle array applicator: an applicator body including an upper portion, a lower portion, and an opening extending through the upper portion and the lower portion along an axis, the lower portion configured to be placed adjacent to the skin of a user; an actuator configured to slidably engage the applicator body between an unactuated configuration and an actuated configuration of the applicator; a plunger at least partially disposed within the opening of the applicator body, the plunger including a base and a latch extending from an inner surface of the base, the latch configured to engage a slot disposed in the upper portion of the applicator body when the applicator is in the unactuated configuration to retain the plunger at least partially within the opening of the applicator body; a stored energy device disposed between the base of the plunger and an inner surface of the actuator, the stored energy device configured to be compressed and biased as the applicator is manipulated from the unactivated configuration to the activated configuration; A microneedle array applicator comprising: Axial compression of the actuator and the applicator body operates the applicator from the unactuated configuration to the actuated configuration, and actuating the applicator from the unactuated configuration to the actuated configuration causes the actuator to inwardly bias the latch, disengaging the latch from the slot in the applicator body and releasing the plunger. Microneedle array applicator.

2. The applicator of claim 1 , wherein the stored energy device comprises at least one of a wave spring, a conical coil spring, a coil spring, or an extension spring.

3. 3. An applicator according to claim 1, wherein the actuator further includes an actuator arm extending from an upper portion of the inner surface of the actuator that engages with an upper tab of the applicator body to retain the actuator on the applicator body, the upper tab extending from the lower portion of the applicator body.

4. 4. The applicator of claim 1, wherein the actuator includes a cavity disposed within the inner surface of the actuator along the axis, the cavity configured to bias the latch inward and disengage the latch from the slot in the applicator body.

5. 5. The applicator of claim 1, wherein the applicator body further includes a recess disposed in the lower portion of the applicator body configured to accommodate a portion of the lower surface of the actuator.

6. An applicator as described in any one of claims 1 to 5, wherein the applicator body further includes a rib arranged on an outer surface of the upper portion of the applicator body extending in a direction substantially parallel to the axis, the rib being configured to be slidably received by a slot arranged in the inner surface of the actuator for the purpose of preventing the actuator from rotating around the axis when the actuator is operated along the axis relative to the applicator body.

7. 7. The applicator of claim 1, wherein the plunger further includes second and third latches extending from the inner surface of the base, each of the second and third latches configured to engage with the slot disposed in the upper surface of the applicator body to retain the plunger at least partially within the opening of the applicator body when the applicator is in the unactuated configuration, and wherein operating the actuator from the unactuated configuration to the actuated configuration causes the actuator to deflect the second and third latches inward, disengaging the second and third latches from the slots of the applicator body and releasing the plunger.

8. 8. The applicator of claim 1, wherein the plunger further includes an arm extending from the base and configured to engage with a protrusion positioned within the opening of the applicator body to retain the plunger on the applicator body.

9. 9. The applicator of claim 1, wherein the outer surface of the base of the plunger is configured to contact and drive the microneedle array through a lower surface of the lower portion of the applicator body when the applicator is operated from the unactivated configuration to the activated configuration.

10. The applicator of claim 9 , wherein the outer surface of the base of the plunger is configured to be in contact with the microneedle array when the applicator is in the unactuated configuration.

11. 1. A system comprising a microneedle array and a microneedle array applicator, the applicator comprising: an applicator body including an upper portion, a lower portion, and an opening extending through the upper portion and the lower portion along an axis, the lower portion configured to be placed adjacent to the skin of a user; an actuator configured to slidably engage the applicator body between an unactuated configuration and an actuated configuration of the applicator; a plunger at least partially disposed within the opening of the applicator body, the plunger including a base and a latch extending from an inner surface of the base, the latch configured to engage a slot disposed in the upper portion of the applicator body when the applicator is in the unactuated configuration to retain the plunger at least partially within the opening of the applicator body; a stored energy device disposed between the base of the plunger and an inner surface of the actuator, the stored energy device configured to be compressed and biased as the applicator is manipulated from the unactivated configuration to the activated configuration; Including, The applicator is configured such that axial compression of the actuator and the applicator body operates the applicator from the unactuated configuration to the actuated configuration, such that operating the applicator from the unactuated configuration to the actuated configuration causes the actuator to inwardly bias the latch, disengaging the latch from the slot in the applicator body and releasing the plunger. system.

12. The microneedle array: a plurality of microneedles disposed on a substrate; a backing layer; an adhesive layer disposed on the backing layer between the backing layer and the substrate of the microneedle array; The system of claim 11 , comprising:

13. 13. The system of claim 11, wherein the microneedle array is positioned within the opening in the applicator body of the applicator when the applicator is positioned in the unactuated configuration.

14. 14. The system of claim 11, wherein the microneedle array is retained within the opening of the applicator by tabs extending from an inner surface of the lower portion of the applicator body.

15. 15. A system according to any one of claims 11 to 14, wherein the actuator of the applicator further includes an actuator arm extending from an upper portion of the inner surface of the actuator that engages with an upper tab of the applicator body of the applicator to retain the actuator on the applicator body, the upper tab extending from the lower portion of the applicator body.

16. 16. The system of claim 11, wherein the actuator includes a cavity disposed within the inner surface of the actuator along the axis, the cavity configured to bias the latch inward to disengage the latch from the slot in the applicator body.

17. 17. The system of claim 11, wherein the applicator body of the applicator further includes a recess disposed in the lower portion of the applicator body configured to accommodate a portion of the lower surface of the actuator.

18. 18. The system of any one of claims 11 to 17, wherein the plunger of the applicator further includes second and third latches extending from the inner surface of the base, each of the second and third latches configured to engage with the slot disposed in the upper surface of the applicator body to retain the plunger at least partially within the opening of the applicator body when the applicator is in the unactuated configuration, and wherein operating the actuator from the unactuated configuration to the actuated configuration causes the actuator to deflect the second and third latches inward, disengaging the second and third latches from the slots of the applicator body and releasing the plunger.

19. placing a microneedle array within an opening in an applicator body of an applicator, the opening extending along an axis through upper and lower portions of the applicator body, the applicator further including an actuator slidably engaged with the applicator body and a plunger at least partially disposed within the opening of the applicator body; placing the applicator adjacent to the skin of a user; manipulating the applicator from an unactuated configuration to an actuated configuration, the manipulating the applicator from the unactuated configuration to the actuated configuration including axially compressing an actuator of the applicator and the applicator body along the axis, a stored energy device disposed between a base of the plunger and an inner surface of the actuator being compressed and biased when the applicator is operated from the unactuated configuration to the actuated configuration, the actuator inwardly deflecting a latch extending from an inner surface of the base of the plunger to disengage the latch from a slot disposed in the upper portion of the applicator body and releasing the plunger; A method comprising:

20. 20. The method of claim 19, wherein manipulating the applicator from the unactuated configuration to the actuated configuration causes the plunger to drive the microneedle array toward the skin of the user, thereby delivering the microneedle array to the skin.

Images