Microneedle patch with force feedback indicator

Abstract

In one embodiment, a microneedle patch is provided, the microneedle patch comprising an array of microneedles; a base substrate from which the microneedles extend; and a force feedback indicator (FFI) attached to the base substrate. The FFI includes a substrate and a button having an upper surface and a side surface, where the button is configured to translate within the substrate from a pre-actuated position into an actuated position, where the side surface is substantially visible in the pre-actuated position and substantially invisible in the actuated position. The side surface has a different color than the upper surface and / or the substrate, which helps visually confirm the actuation status of the button, which may help indicate whether the microneedle patch is ready for use or has been used. The FFI may be configured to provide tactile, auditory, and visual confirmation of sufficient force applied to a microneedle patch to enable insertion of the microneedle.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 405,932, filed Sep. 13, 2022, which is incorporated herein by reference. BACKGROUND OF THE INVENTION

[0003] This application generally relates to the field of microneedle patches for delivering bioactive agents or other suitable substances into biological tissue, such as delivering vaccines, contraceptives, or other drugs to the skin of a human.

[0004] There is a desire to provide improved microneedle patches that can simplify and improve the delivery of vaccines and other reagents, store the reagents in a dry form, can be easily and consistently manually applied, e.g., without a separate applicator device, can deliver a reagent payload into the skin in a short duration, e.g., such that the patch can be removed from the skin within minutes of application to the skin, do not leave sharp microneedles after application of the reagent payload, and include a force feedback indicator to confirm that sufficient manual force has been applied to the patch to ensure full or proper insertion of the microneedles into the skin, and / or include an indicator to show that the microneedle patch has been used.

[0005] There is also a desire to provide new and improved systems for packaging and protecting the microneedles of a microneedle patch prior to use. Specifically, it may be important to provide such a system in a compact design, where the microneedle patch product must be kept cold during transportation and storage prior to use. SUMMARY OF THE INVENTION

[0006] In one aspect, there is provided a microneedle patch comprising: an array of microneedles; a substrate having a first side and an opposite back side, the microneedles extending from the first side; and a force feedback indicator (FFI) attached to the back side of the substrate, wherein the FFI includes a base and a button having an upper surface and a side surface, wherein the button is configured to translate within the base from a pre-actuated position to an actuated position, wherein the side surface is substantially visible in the pre-actuated position and substantially invisible in the actuated position. The FFI is preferably configured to further provide a tactile and / or audible confirmation of sufficient force applied to the microneedle patch to effect insertion of the microneedles. In certain embodiments, the side surface has a color different from the color of the upper surface and / or the color of the base, which aids in visually confirming the actuated state of the button, which can help indicate whether the microneedle patch is ready for use or has been used.

[0007] In another aspect, there is provided a microneedle patch comprising: an array of dissolvable microneedles; a base substrate having a first side and an opposing back side from which the microneedles extend; and a wear time indicator (WTI) attached to the back side of the base substrate and configured to provide a visual indication that the microneedle patch has been worn on the user's skin for a period sufficient to effect dissolution of the microneedles after insertion of the microneedles into the user's skin. (The period is the wear time.) In a particular embodiment, the WTI comprises a dye blister and a core assembly, wherein the dye blister has a rupturable dye reservoir configured to release dye into the core assembly upon application of a force to the microneedle patch to effect insertion of the microneedles. The position of the dye within the core assembly corresponds to the wear time.

[0008] In another aspect, there is provided a microneedle patch comprising: an array of microneedles; a base substrate having a first side and an opposing back side from which the microneedles extend; and a force feedback indicator (FFI) including a base and a button, wherein the base substrate and the array of microneedles are attached only to the button of the FFI, wherein the button is configured to translate from a pre-actuated position to an actuated position within the base, and wherein the base of the FFI is sized such that in the pre-actuated position, the array of microneedles is positioned within an opening recessed in the lower surface of the base of the FFI. In a particular embodiment, at least an upper portion of the button in the pre-actuated position is raised above the base, and at least an upper portion of the button in the actuated position is flush with or recessed into the base. The button may have an upper surface and a side surface, wherein the side surface is substantially visible in the pre-actuated position and substantially invisible in the actuated position. In some embodiments, the button of the FFI includes a latch, and the housing includes (i) a first latch socket configured to receive the latch and releasably hold the button in the pre-actuated position, and (ii) a second latch socket configured to receive the latch and non-releasably hold the button in the actuated position. In a particular embodiment, the microneedle patch is configured such that a first minimum force on the button effectively moves the latch out of the first latch socket and causes the button to shift towards the base and begin insertion of the microneedles into the tissue surface; and such that a second minimum force on the button, which may be greater than the first minimum force, effectively moves the latch into the second latch socket and triggers a tactile signal and / or an audible signal that sufficient force has been applied to the microneedle patch to effect full insertion of the microneedles into the tissue surface.

[0009] In yet another aspect, there are provided microneedle patch packaging units and systems. In one embodiment, there is provided a microneedle patch packaging system comprising: (i) a microneedle patch having an adhesive surface; and (ii) a foil or other pouch material adhered to the adhesive surface, wherein the foil or other pouch material is folded and sealed to form a sealed pouch surrounding at least one of the microneedle patches. In another embodiment, there is provided a microneedle patch packaging unit comprising: (i) a microneedle patch having a handling tab; (ii) a packaging tray having a cavity in which the microneedle patch is disposed; and (iii) a foil or other film attached to the tray to seal the cavity, wherein the packaging system is configured such that when the foil or other film is removed from the tray, the handling tab is positioned towards the opening of the cavity to facilitate grasping the handling tab to remove the microneedle patch from the packaging tray. In some embodiments, this advantageous handling tab position can be achieved by a design in which the handling tab is folded over the top of the microneedle patch within the sealed tray and partially unfolds itself when the foil or other film is removed from above the cavity. In another embodiment, there is provided a packaging system comprising a plurality of these microneedle patch packaging units, wherein the edges of the packaging trays of each packaging unit are releasably attached at the edges of at least one other packaging tray of another packaging unit, such as where the releasably attached edges are defined by perforation lines in a shared sheet material. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The detailed description is set forth with reference to the accompanying drawings. The use of the same reference numerals may indicate similar or identical items. Various embodiments may utilize elements and / or components in addition to those shown in the figures, and some elements and / or components may not be present in various embodiments. The elements and / or components are not necessarily drawn to scale.

[0011] Figure 1A and 1B are a perspective view and an exploded view, respectively, of a microneedle patch with FFI according to one or more embodiments of the present disclosure.

[0012] Figure 2A is a side view of a microneedle patch with FFI according to one or more embodiments of the present disclosure.

[0013] Figure 2B is according to one or more embodiments of the present disclosure Figure 2A upper perspective view of the microneedle patch shown in

[0014] Figure 2C is according to one or more embodiments of the present disclosure Figure 2A bottom view (microneedle array side) of the microneedle patch shown in

[0015] Figure 2Dis according to one or more embodiments of the present disclosure Figure 2A Top view (button side) of the microneedle patch shown in

[0016] Figure 3A Perspective view of a storage tray for a microneedle patch according to one or more embodiments of the present disclosure.

[0017] Figure 3B is according to one or more embodiments of the present disclosure in which the microneedle patch is stored Figure 3A Bottom perspective view of the storage tray.

[0018] Figure 3C is according to one or more embodiments of the present disclosure in which the microneedle patch is stored Figure 3A Top perspective view of the storage tray.

[0019] Figure 4A Top perspective view of a microneedle patch according to one or more embodiments of the present disclosure, in which the upper portion of the button of the FFI in the pre-actuation position is raised above the base of the FFI. The downward arrow indicates the force applied to the button.

[0020] Figure 4B is according to one or more embodiments of the present disclosure Figure 4A Top perspective view of the microneedle patch shown in , but in which the upper portion of the button of the FFI in the actuated position is slightly recessed into the base of the FFI.

[0021] Figure 5A Side cross-sectional view of a microneedle patch according to one or more embodiments of the present disclosure, in which the button of the FFI in the pre-actuation position is raised above the base of the FFI and the microneedle array is recessed within the base.

[0022] Figure 5B is according to one or more embodiments of the present disclosure Figure 5A Side cross-sectional view of the microneedle patch, but in which the button of the FFI in the actuated position is recessed into the base of the FFI and the microneedle array extends from the base.

[0023] Figures 6A - 6C Micrograph of dissolving microneedles according to one or more embodiments of the present disclosure.

[0024] Figures 7A - 7C Depicts the process of using a microneedle patch according to one or more embodiments of the present disclosure, in which its microneedles are inserted into biological tissue, dissolve, and separate from the patch backing.

[0025] Figure 8 Depicts steps in a molding process according to one or more embodiments of the present disclosure, in which droplets are placed onto a mold for a segmented microneedle array.

[0026] Figure 9 is a bottom perspective view of a microneedle patch having a segmented microneedle array according to one or more embodiments of the present disclosure.

[0027] Figure 10A is a perspective view of a packaging unit according to one or more embodiments of the present disclosure, the packaging unit containing a microneedle patch stored in a rectangular storage container (tray) and surrounded by a removable lid material, wherein the storage container and the lid material are transparent and shown in dashed lines.

[0028] Figure 10B is a perspective view of a packaging system according to one or more embodiments of the present disclosure, the packaging system including Figure 10A the ten packaging units shown in, wherein nine units are attached to at least one other unit along a docking side edge. Another unit is shown separated, having been separated from the other units along a perforation line.

[0029] Figure 10C is a perspective view of another packaging system according to one or more embodiments of the present disclosure, the another packaging system including Figure 10B a box-shaped stack of five packaging systems shown in, wherein the boxes are transparent and shown in dashed lines.

[0030] Figure 11A is a perspective view of another packaging system according to one or more embodiments of the present disclosure, the another packaging system including a plurality of microneedle packaging units, each microneedle packaging unit including a trapezoidal storage tray, and wherein each unit is shown attached to at least one other unit along a docking side edge.

[0031] Figure 11B is according to one or more embodiments of the present disclosure Figure 11A a perspective view of an open microneedle packaging unit among the microneedle packaging units shown in, wherein the microneedle patch is positioned in a cavity of the tray (with the lid material removed).

[0032] Figure 12 is an exploded view of a wear-time indicator for a microneedle patch according to one or more embodiments of the present disclosure.

[0033] Figures 13A - 13D shows a time-lapse photograph of the Figure 12 wear-time indicator in use according to one or more embodiments of the present disclosure. DETAILED DESCRIPTION

[0034] Improved microneedle patches and systems have been developed to provide enhanced usability, convenience, handling / storage capabilities, and / or functionality.

[0035] The microneedle patch includes an array of microneedles extending from a base substrate that is connected to other components that facilitate the handling and insertion of the microneedles. Those components typically include a tape layer that includes an adhesive side and a handling tab, and may further include a force feedback indicator (FFI) or a wear time indicator (WTI). In certain embodiments, the FFI and WTI are not electronic. In fact, they operate mechanically and are typically made of relatively inexpensive polymer components that can be produced in high-volume manufacturing processes.

[0036] In some preferred embodiments, the microneedles include a substance of interest and a water-soluble matrix material in which the substance of interest is dispersed.

[0037] In some embodiments, a force feedback indicator (FFI) is attached to the rear side of the base substrate, where the FFI includes a base and a button having an upper surface and a side surface, where the button is configured to translate within the base from a pre-actuated position to an actuated position, where the side surface is substantially visible in the pre-actuated position and substantially invisible in the actuated position. The FFI is preferably configured to further provide a tactile and / or audible confirmation of sufficient force applied to the microneedle patch to effect insertion of the microneedles.

[0038] In some embodiments, the microneedle patch includes: an array of microneedles; a base substrate having a first side and an opposite rear side, the microneedles extending from the first side; a tape layer that includes an adhesive side and a handling tab; and a force feedback indicator (FFI) that is secured to the tape layer. The FFI can be configured to provide an audible-tactile and / or visual signal when the force applied by a user to the patch during application of the patch to biological tissue to insert the solid microneedles into the biological tissue meets or exceeds a predetermined threshold. The tape layer can be a double-sided adhesive, a plastic film having an adhesive disposed on either or both sides, or a double-sided tape.

[0039] In some embodiments, the tape layer includes an aperture through which a central portion of the base extends, and the microneedle array is mounted on this central portion to raise the microneedles away from the surrounding tape layer and its adhesive side, which facilitates insertion of the microneedles when the adhesive side is pressed against and adheres to the skin surface. The raised microneedles can also provide the force required to maintain the microneedle array within the skin (i.e., provide a pressing force on the microneedles) for the duration of the patch wear time.

[0040] Some examples of suitable microneedle arrays and methods of manufacturing the same that can be used with the microneedle patches and packaging systems of the present invention are described in the following documents: U.S. Patent 10,265,511; U.S. Patent No. 10,828,478; U.S. Patent No. 10,828,478; U.S. Patent No. 10,940,301; and US20200238065A1, which are incorporated herein by reference.

[0041] The microneedle patch can include an array that includes any suitable number of microneedles, such as from 10 to 10,000 microneedles, such as from 50 to 1000 microneedles. The periphery of the array can have an external shape that is circular (e.g., as shown in FIG. 1) or hexagonal (e.g., as shown in Figures 2A - 2D ), both of which can extend from a circular or other shaped substrate.

[0042] In a preferred embodiment, the microneedles are solid microneedles that contain a substance of interest (e.g., an active pharmaceutical ingredient (API)), which dissolves in vivo after the microneedles are inserted into biological tissue, such as into a patient's skin. For example, the substance of interest can be mixed in a water-soluble matrix to form solid microneedles that extend from a substrate, or the substance of interest can be in the form of a coating on a microneedle substructure that extends from the substrate. In either case, the substance of interest can be provided in a formulation that can be referred to herein as "soluble." In embodiments where the substance of interest and the matrix material in which the substance of interest is dispersed form the structure of the microneedles, the matrix material is also preferably soluble in vivo such that the entire portion of the microneedles inserted into biological tissue dissolves in vivo (e.g., about 90% to 95% of the total length of the microneedles). In embodiments where the substance of interest is part of a coating on a microneedle substructure, the substructure can also dissolve in vivo.

[0043] The microneedles can have a height ranging from about 100 μm to about 2000 μm, from about 100 μm to about 1500 μm, from about 100 μm to about 1000 μm, or from about 500 μm to about 1000 μm. The microneedles can be arranged on the substrate at any suitable density.

[0044] Microneedle Patch with Force Feedback Indicator (FFI)

[0045] FIG. 1 shows an exemplary microneedle patch having an FFI and a plurality of solid microneedles. Patch 100 includes a substrate 102 having a plurality of microneedles 104. The plurality of microneedles 104 are attached to the FFI 106. The microneedles 104 and the FFI 106 can be attached to the backing layer 108 via an opening 110 therein. That is, the backing layer 108 can include an opening 110 sized and shaped to receive the plurality of microneedles 104 and the FFI 106 within the opening 110. In some embodiments, the substrate 102 that holds the plurality of microneedles 102 is attached to the FFI 106 by a first adhesive layer 112, and the FFI 106 is attached to the backing layer 108 by a second adhesive layer 114. In other embodiments, the substrate 102 and the backing layer 108 are integrally formed with the FFI 106.

[0046] In some embodiments, the backing layer 108 can include a tab portion 116 that extends laterally away from the microneedles 104. Alternatively, the tab portion can be disposed in a separate layer (not shown). Thus, the tab portion can be in the same plane or a different plane from the backing layer. Unless otherwise explicitly provided, "backing layer" and "handle layer" can be used interchangeably in this disclosure. The tab portion 108 can advantageously enable a patient or user to handle the patch 100 without contacting the "body portion" of the patch defined by the base substrate 102 and the plurality of microneedles 104. For example, the size and shape of the tab portion 116 can be designed to allow a person to manually grasp the tab portion 116 (e.g., between the thumb and fingers). Although the tab portion 116 is shown in FIG. 1 as extending laterally and asymmetrically from the backing layer 108, other shapes and sizes are possible.

[0047] In some embodiments, an adhesive (not shown) is disposed on the microneedle 104 side of the backing layer 108 to assist in adhering the patch 100 to a patient's skin during application. The adhesive can also be used to adhere the patch to a tray or container covering the plurality of microneedles during transportation and storage, and for disposal after its use. In one embodiment, the tab portion 116 is substantially free of an adhesive layer such that a person handling and applying the patch can do so without contacting the adhesive layer. In some embodiments, the adhesive layer can be disposed over substantially the entire side of the backing layer 108 that includes the tab portion 116. A covering portion (not shown) can be disposed over the adhesive layer over the tab portion 116 such that a person grasping the patch 100 by the tab portion does not contact a majority of the adhesive layer.

[0048] FFI 106 includes a base 118 and a button 120 that is configured to translate within the base 118. The base 118 can include a central portion 122, an outer portion 124, and an intermediate portion 126 that is located between and connects the central portion 122 and the outer portion 124. The base substrate 102 carrying the microneedles 104 is attached to the central portion 122 of the base 118 via a first adhesive layer 112. The outer portion 124 of the base 118 can be attached to the rear side (i.e., the side opposite the microneedles) of the backing layer 108 via a second adhesive layer 114. That is, the second adhesive layer 114 can have an annular shape such that the second adhesive 114 can be placed around the central portion 122 and the intermediate portion 126 and placed onto the outer portion 124.

[0049] The button 120 can be slidably attached to the base 118 by one or more slots 128 disposed circumferentially around the middle portion 126 of the base 118. That is, relative to FIG. 1, the button 120 can have one or more upwardly extending protrusions 130 configured to be received within one or more slots 128 of the base 118. Each of the one or more protrusions 130 can also include a lip 132 to secure the protrusion 130 within the slot 128, which can prevent the button 120 from being accidentally removed from the base 118.

[0050] The button 120 can also include an upper surface 134 and a side surface 136. The button 120 can be translated from a pre-actuation position to an actuated position, where the side surface 136 is visible in the pre-actuation position and substantially invisible in the actuated position. For example, as Figure 4A shown in FIGS. 4C, when the patch 100 is assembled, the button 120 can initially project above the backing layer 108 and the base 118 of the feedback indicator. When a downward force is applied to the top of the button 120 (i.e., the patient or user presses the button 120), the button 120 can move downward into the central portion 122 of the base 118. When the button 120 is fully translated from the pre-actuation position to the actuated position, the button 120 is fully seated within the base 118 and is no longer visible. In some embodiments, the side surface 136 can be formed of a material having a different color than the remainder of the feedback indicator 106, which can help the user better identify when the button 120 has been fully translated from the pre-actuation position to the actuated position, thereby indicating that the plurality of microneedles 104 have been at least partially inserted into the tissue.

[0051] The FFI 106 also includes an auxiliary mechanism for providing feedback to the user to assist in the proper and effective use of the microneedle patch. For example, in some cases, translating the button 120 to the actuated position may not be sufficient to fully insert the microneedles 104 into the tissue. That is, actuating the button 120 from the pre-actuation position to the actuated position may only be sufficient to penetrate the tissue and partially insert the microneedles 104, thus requiring additional force to fully insert the microneedles 104 into the skin. In other cases, it may be advantageous to utilize an auxiliary feedback mechanism to enable the patient or user to ensure that the microneedles have been fully inserted. The auxiliary feedback can be provided in various forms or combinations, including tactile (e.g., a detectable sensation felt by the person applying the patch or the patient), auditory (e.g., the presence, absence, or change in sound).

[0052] Feedback can be provided to various "users", including but not limited to the person to whom the microneedle patch is applied (e.g., the patient) and any other person who applies the microneedle patch to the person (healthcare provider, caregiver, parent, guardian).

[0053] In a preferred embodiment, the FFI indicates to the user the amount of force and / or pressure applied to the patch during its application. For example, in one embodiment, the indicator is configured to provide a signal when the force applied by the user to the patch (during the process of applying the patch to the patient's skin to insert the microneedles into the patient's skin) meets or exceeds a predetermined threshold. For example, the predetermined threshold can be the minimum force required to effectively apply a particular microneedle patch to the patient's skin or some amount greater than the minimum force. That is, the predetermined threshold is the force required to properly, e.g., substantially insert the microneedles into the patient's skin.

[0054] The FFI can signal to the user in a variety of different ways that the predetermined threshold has been met or exceeded. In one embodiment, the FFI can change from its initial configuration to its signaling configuration upon receiving a force that meets or exceeds the predetermined threshold.

[0055] In some embodiments, the FFI 106 also includes a snap dome 138 disposed within the button 120, which can be designed to contract (deform) when a sufficient force that meets or exceeds the predetermined threshold is applied. The contraction can make a clicking sound and / or can be felt by the user's finger that is used to apply the patch. In this way, the snap dome provides the user with a tactile, visual, and audible signal that the threshold force has been met or exceeded and that the patch has been properly applied to the patient's skin. The snap dome can be a bistable snap dome. The FFI is preferably configured to undergo an irreversible shift by integrating the snap dome with other components, such as the button and the substrate that are locked together as described herein.

[0056] Figures 5A - 5B Another microneedle patch with an integrated FFI is shown. The microneedle patch 400 includes a base substrate 402 having an array 404 of microneedles. The base substrate 402 is attached to the button 416 of the FFI 406 only at the bottom surface of the button 416. The base substrate 402 can be attached to an adhesive layer (not shown) or the base substrate 402 can be integrally formed with the button 416.

[0057] The microneedle patch 400 also includes a backing layer 408, which is attached to the base 114 of the FFI 406 at the lower surface 417 of the base and the upper surface of the backing layer. For example, the base of the FFI can be attached via an adhesive disposed on the top side of the backing layer 408. In some embodiments, the backing layer 408 includes a tape disposed thereon (e.g., a film or other thin structure, including a polymer support / base layer and an adhesive layer (e.g., a pressure-sensitive adhesive known in the art). In this way, the FFI 406 can be directly attached to the backing layer 408.

[0058] The backing layer 406 includes a tab portion 410 that extends laterally away from one side of the substrate 414 to assist a user in handling the patch 400 without contacting the substrate or the microneedles 404. Advantageously, however, the microneedles 404 are disposed within a recess 412 defined by the substrate 414 (and the opening in the backing layer 408) to further protect the microneedles from unnecessary contact with any person or thing until the microneedles are intended to be inserted into the skin or another tissue surface.

[0059] In use, the array of microneedles 404 and the button 416 translate together through / from the recess 412 for insertion. To administer the microneedle array 404, the button 416 is depressed downwardly and displaced from a pre-actuation position in which the microneedles 404 are disposed within the recess 412 to an actuated position in which the microneedles 404 project from the recess 412.

[0060] In the pre-actuation position, the button 416 is held in place within the substrate 414 by a latch 420 that extends laterally from the button 416 and is received within a first latch socket 418 in the housing. The latch 420 releasably holds the button 416 in the pre-actuation position, as Figure 5A shown. The housing (substrate) also includes a second latch socket 422 that is configured to receive the latch 420 and preferably non-releasably hold the button in the actuated position. The latch and socket can be configured such that a first minimum force on the button effectively removes the latch from the first latch socket and displaces the button toward the substrate and begins inserting the microneedles into the tissue surface, and a second minimum force on the button effectively moves the latch into the second latch socket and triggers a tactile and / or audible signal that sufficient force has been applied to the microneedle patch to effect full insertion of the microneedles into the tissue surface. In some preferred embodiments, the first minimum force is less than the second minimum force.

[0061] In some other embodiments, the first minimum force on the button effectively (i) removes the latch from the first latch socket and displaces the button toward the substrate and begins inserting the microneedles into the tissue surface; and (ii) moves the latch into the second latch socket and triggers a tactile and / or audible signal that sufficient force has been applied to the microneedle patch to effect full insertion of the microneedles into the tissue surface.

[0062] In some embodiments, the button 416 or at least its side surface has a material that is a significantly different color than the substrate 414 such that a user can more easily or quickly identify when the button 416 has fully reached the actuated position.

[0063] The microneedle patch 400 may optionally further include an auxiliary feedback mechanism that indicates to the user that sufficient force has been applied to successfully deliver the microneedles to the tissue, similar to that described with respect to FIG. 1. That is, in some cases, the force required to translate the button may not be sufficient to insert the microneedles into the tissue. The auxiliary feedback mechanism can be triggered when sufficient force is applied to insert the microneedles.

[0064] In some embodiments, the microneedle patch 400 further includes a release liner or other material (not shown) that covers the notch 412, for example, by releasably adhering to the bottom of the backing layer 408 to further protect the microneedles prior to application of the patch. The release thread will be removed prior to placing the microneedle patch against the skin.

[0065] In some alternative embodiments, the latch and latch socket features can be replaced or enhanced with other force setting / actuating mechanisms, such as, for example, plastic snaps, brittle fractures, plastic snap latch deformations, or snapping into notches / recesses.

[0066] Microneedle Storage System

[0067] As Figures 3A - 3C shown, the microneedle patch 100 can be accommodated on a tray 300 having an inner surface 302 that defines a recessed area 304 therein. The size of the recessed area 304 can be set to non - contactingly receive and surround an array 104 of microneedles. The tray 300 can also be releasably adhered to the microneedle patch 100 to prevent the patch 100 from moving within the tray 300. That is, an adhesive layer (not shown) of the microneedle patch 100 can be releasably fixed to the inner surface 302 of the tray 300. Since the contact between the tray and the microneedle patch is substantially limited to the adhesive layer and / or the backing, the integrity of one or more microneedles is advantageously maintained during storage. Additionally, the tray can also protect one or more microneedles from moisture, gases, or other contaminants that may degrade the substance of interest, shorten the shelf life, or reduce the effectiveness of the substance of interest.

[0068] In some embodiments, a tab portion 116 of the microneedle patch 100 can extend from the tray 300 to facilitate removal of the microneedle patch 100 from the tray. The tray 300 can also include a flange 306 to improve user access to the microneedle patch 100 stored within the tray 300.

[0069] The tray can be of various shapes and sizes, such as a rectangular shape, a planar shape with a cover, or a partially oval shape. The tray can further include one or more additional features having various functions or for imparting a desired aesthetic to the tray. For example, the tray can include one or more depressions, holes, or cuts. Such features can assist in removing the microneedle patch from the tray. A recessed area for receiving one or more microneedles can also be located in the tray such that at least a portion of the tab extends above the perimeter of the tray.

[0070] A variety of materials can be used to manufacture the trays provided herein, non-limiting examples of which include polymers (e.g., polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP), polyvinylidene fluoride (PVDF), polyvinyl fluoride (PVF), polyethylene, or polypropylene), metallized polymers, elastomers, non-woven and woven materials, paper-based materials, foams, metals, or foils, etc. In some embodiments, the tray can be formed from a composite material or a multi-layer material. For example, the multi-layer material can include one or more layers that impart desired structural properties and one or more layers that impart desired moisture and gas barrier properties.

[0071] The tray can be configured to accommodate a single patch or multiple patches (e.g., 2, 3, 4, 5, 6, 7, 8, 10, 12, or 20 patches, or more or less). The tray can include a plurality of notches, where each notch corresponds to one of the microneedle patches. The tray can also include one or more weakening lines (e.g., perforations, score lines, etc.) such that a portion of the tray can be separated from other portions of the tray. In some embodiments, the patches can be stored on one side of the tray, while in other embodiments, the patches can be stored only on one side of the tray (e.g., in recessed areas on both sides of the tray).

[0072] These trays alone may be sufficient to protect the patch before use; however, additional features can also be used. For example, one or more trays can be placed in a flexible container (e.g., a bag) and / or a rigid container (e.g., a box). In some embodiments, a lid can be placed on the tray to protect the microneedle patch before use. Such a lid can have the same or a different material as the tray and can be sealed to the perimeter of the tray (i.e., using heat sealing, cold sealing, or a pressure-sensitive adhesive). In one embodiment, a desiccant can be placed in the recessed area or in the flexible or rigid container that houses the tray. The desiccant can alternatively or additionally be part of the tray itself. For example, the desiccant material can be included in the material forming the structure of the tray (e.g., dispersed therein or coated thereon). For example, the tray can be formed from a desiccant polymer known in the art.

[0073] The tray can be formed using a variety of different methods, non-limiting examples of which include various molding methods (e.g., thermoforming, injection molding, stamping, casting), 3D printing, etc.

[0074] In some embodiments, as Figures 10A - 10C shown in, as regarding Figures 6A - 6B the microneedle patch 400 described can be folded in half and stored in a sealed bag 700. In some embodiments, as Figure 10A shown in, the base substrate 408 of the microneedle patch 400 can be folded at the point where the feedback indicator 406 is attached to the base substrate 408 and again near the interface between the tab portion 410 and the base substrate 408. The result is a compact patch 400 that can be more easily accommodated in a compact container or bag.

[0075] In an embodiment, the bag material (e.g., foil) 702 can be adhered to the microneedle patch 400. That is, the microneedle patch 400 can have an adhesive layer (not shown) on the bottom side of the backing layer 408. Thus, the bag material 702 can be adhered to the adhesive surface of the backing layer 408 and fold over itself to form the bag 700. In some embodiments, the bag material 702 can completely surround the microneedle patch 400, i.e., the bag 700 is formed entirely of the bag material 702. In other embodiments, the bag material 702 surrounds the microneedle patch 400 on all sides except the side covered by the lid 704. The lid 704 can be sealed or otherwise attached to the bag material 702.

[0076] As Figure 10B shown in, a plurality of trays 700 can be arranged in an array to form a packaging unit 710. The trays 700 within each packaging unit 710 can be releasably attached to each adjacent tray 700 within the packaging unit 710. For example, the edges 706 of each tray 700 can be defined by a perforation line in a shared sheet material (which forms the lid 704) such that the corresponding trays 700 can be separated from each other along the edges 706. Each tray 700 can also include an opening tab 708 to facilitate removal of the lid 704. In some embodiments, a plurality of packaging units 710 can be stacked and stored in a box 712 or other storage container for long-term storage and / or transportation of the microneedle patches.

[0077] In other embodiments, as Figures 11A - 11BAs shown, the microneedle patch 100, as described with respect to FIG. 1, can be placed in a tray 800, the size and shape of which are configured to receive the microneedle patch 100. The microneedle patch 100 can be located within a cavity 802 defined within a base portion 804 of the tray 800. In some embodiments, the bottom 806 of the cavity 802 is angled such that the tab portion 116 of the microneedle patch 100 can be easily grasped to remove the patch 100 from the tray 800. That is, the angled bottom 806 of the cavity 802 can cause the tab 116 of the microneedle patch 100 to be angled in an upward direction such that the tab is positioned near the opening of the cavity 802. In some embodiments, the tray 800 can be sealed with a lid 808 that at least covers the cavity 802. However, it is preferred that the lid 808 covers the entire base 804 of the tray 800. The lid 808 can be formed of foil or another suitable film material that can be peeled away from the tray 800 when the patch 100 is ready for use.

[0078] As Figure 11A As shown, a plurality of trays 800 can form a packaging unit 810, where the edge 812 of one tray 800 is releasably attached to the edge 812 of each adjacent tray 800. In some embodiments, the releasably attached edges 812 are defined by perforation lines in a shared sheet material, i.e., the sheet material used to form the lids 808 of the trays 800. The packaging units 810 can be stacked and stored in a box or other storage container, similar to the packaging units 710.

[0079] Microneedle Preparation

[0080] The microneedle patches and methods of the present invention can be used to formulate various substances for delivery to biological tissue. The microneedles can be formed of one or more substances of interest and one or more excipients. As used herein, the term "substance of interest" includes active pharmaceutical ingredients, allergens, vitamins, cosmeceuticals, nutricosmetics, markers (e.g., colored dyes, inks, pigments, or radioactive dyes or markers), and other materials desired to be introduced into the skin or another biological tissue. In some embodiments, the substance of interest is a prophylactic, therapeutic, or diagnostic agent useful in medical or veterinary applications. In some embodiments, the substance of interest is a bioactive agent that can be referred to herein as an API, which can be a prophylactic or therapeutic substance. The API can be selected from suitable proteins, peptides, and fragments thereof, which can be naturally occurring, synthetic, or produced recombinantly. In some embodiments, the substance of interest includes vaccines.

[0081] The substance of interest can be included in the formulation together with one or more excipients and other additives used in pharmaceutical formulations. Non-limiting examples of such excipients include stabilizers, buffers, diluents or fillers, adjuvants, surfactants, disintegrants, antioxidants, solubilizers, lyoprotectants, antimicrobial agents, anti-adhesives, colorants, lubricants, viscosity enhancers, glidants, preservatives. The excipients can be those found in existing pharmaceutical products (e.g., those listed in the FDA's inactive ingredients in the approved drug product database) or can be novel, and can effectively perform more than one function (e.g., sugars can be used as stabilizers and diluents, and buffers can be used to buffer the pH and protect the substance of interest from oxidation). One or more selected excipients desirably improve the stability of the substance of interest during drying and storage of the microneedle patch.

[0082] Method of Use

[0083] The microneedle patches provided herein can be self-administered or administered by another individual (e.g., a parent, guardian, minimally trained healthcare provider, professionally trained healthcare provider, and / or others). Different from the prior art microneedle systems, the microneedle patches provided herein can be directly handled and administered by the person applying the patch without the need to use an applicator to apply the required force / pressure.

[0084] Accordingly, the embodiments provided herein further include a simple and effective method of administering the substance of interest with a microneedle patch. The method can include identifying the site of administration and preferably disinfecting the area (e.g., using an alcohol wipe) prior to applying the microneedle patch. If desired, the site of administration can be dried prior to applying the microneedle patch. The patch can be removed from its releasably fixed tray or pouch by grasping the tab portion of the patch between the thumb and finger and peeling the patch from the tray or pouch. The patch is then applied to the patient's skin / tissue, and the patch is manually pressed into the patient's skin / tissue (e.g., using the thumb or finger) by applying sufficient pressure to insert one or more microneedles into the patient's skin / tissue. After administration is complete, the patch can be removed from the patient's skin / tissue by manually grasping the tab portion (e.g., between the thumb and finger), peeling the patch from the patient's skin / tissue, and discarding the patch.

[0085] Figures 6A - 7C Depicts the administration process of the microneedle patch described herein and the dissolution of the microneedles within the patient's skin / tissue after insertion. For example, as Figure 6A and 7A shown, the microneedle patch can be inserted into the patient's skin / tissue such that most of the microneedles are positioned below the surface of the skin / tissue. When the microneedles begin to dissolve, as Figure 6Band 7B As shown, the tip portion of the microneedle can become completely dissolved and dispersed within the tissue, while the base portion of the microneedle remains intact. However, at the point of removing the patch from the patient's skin / tissue, as Figure 6C and 7C shown, the microneedles can completely dissolve within the patient's skin / tissue.

[0086] In some embodiments, a user may use one or more indicators before, during, and / or after applying the microneedle patch. Such indicators can be elements incorporated into the microneedle patch that provide a detectable signal, or can be generated by the user performing one or more actions, such as evaluating the microneedle patch or the patient's skin / tissue after application.

[0087] The user can evaluate various indicators during patch application to signal whether the patch has been properly applied and / or whether it can be removed. For example, in some embodiments, the indicator provides a signal that a predetermined threshold force has been reached or that the microneedles have penetrated / pierced the patient's skin, indicating that the user can stop applying pressure to the patch. In some other embodiments, the indicator can provide a signal at the end of a pressing period, i.e., the period of time after insertion during which the patient or user must continue to apply pressure to the microneedle patch. The pressing period can have a duration between 0 seconds and 120 seconds, such as between 0 seconds and 60 seconds, between 0 seconds and 30 seconds, or between 0 seconds and 10 seconds.

[0088] The above indicators and feedback can also be used to provide evidence that the microneedle patch has been used and can be helpful in cases where the patch has not been properly discarded after use (i.e., thus avoiding attempts to reuse the patch, which would result in ineffective treatment or potentially exposure to biohazardous materials that have been contaminated by the body fluids of a previous patient). Evidence of using the microneedle patch is particularly helpful because microneedles are small structures that are nearly invisible to the naked eye.

[0089] Manufacture

[0090] Methods and systems for manufacturing microneedle patches are also provided. Such methods are preferably performed under a minimum ISO 7 (10,000 class) process or ISO 5 (100 class) process. In some embodiments, the manufacture of solid dissolvable microneedles involves filling a female mold of the microneedles with an aqueous or non-aqueous casting solution of the substance of interest and then drying the casting solution to provide solid microneedles. The filling and drying steps can be repeated with the same or different casting solutions. In some embodiments, droplets of the casting solution can be deposited onto the mold or a portion thereof. The droplets can then be dispersed throughout the mold.

[0091] In some embodiments, the mold contains a single opening onto which droplets can be deposited and the droplets will disperse over all of the microneedle cavities extending from the opening. In other embodiments, as Figure 8 shown in

[0092] Figure 9 , the mold 500 can have several openings 502, each defining a plurality of microneedle cavities 504 therein. Droplets 506 of the casting solution can be deposited onto each section 502 of the mold 500. The droplets 506 can have the same or different casting solutions. That is, in some cases, each of the droplets 506 has the same casting solution such that the resulting microneedle patch has an array of microneedles all having the same formulation. However, in other cases, the droplets 506 can have different casting solutions such that the resulting microneedle array contains microneedles having two or more different formulations. Figure 8 depicts an exemplary microneedle patch 600 formed by a segmented mold, such as

[0093] Although Figures 8 - 9 depicts a mold and microneedle patch having three sections, it should be understood that any number of sections is possible. For example, the mold can have 2, 4, 5, 6, 8, or 10 sections, or any other desired number.

[0094] In some embodiments, it may be desirable to use a multi-step casting process to form the microneedles and the substrate. For example, the tips of the microneedles can be partially filled in a first step with a casting solution comprising the substance of interest (and one or more excipient (matrix) materials), and then one or more subsequent filling steps can be performed with a swelling material (e.g., sodium carboxymethyl cellulose, polyvinyl alcohol, sugars, gelatin, polyvinylpyrrolidone (PVP), cellulose, and / or other matrix materials, including non-dissolving materials such as urethane or acrylic polymers) with or without the same or different substance of interest. After filling and at least partially drying the microneedles in the female mold, an adhesive layer and a backing layer can be applied to the substrate before removing the microneedles from the mold. In some embodiments, the adhesive layer and / or the backing layer are pre-formed before being applied to the substrate, while in other embodiments, the adhesive layer and / or the backing layer can be formed directly in-line. After at least partially drying the microneedles, the microneedles can be removed from the mold. For example, the microneedles can be removed from the mold before being completely dry (e.g., when still in a rubbery state), but when strong enough to be peeled off, and then further dried once removed from the mold to further cure / harden the microneedles. In such embodiments, the microneedles can be dried before or after packaging.

[0095] The microneedle patch can then be attached to a tray and undergo one or more additional packaging steps. For example, the microneedle patch can be applied to the tray and packaged in a foil bag with a desiccant under sterile conditions.

[0096] Microneedle Wear Time Indicator

[0097] The feedback indicator can also provide information to the user (and / or patient) that the microneedle patch has been worn for a sufficient amount of time (i.e., the substance of interest has been released into the target tissue). Such an indicator can be particularly useful for providing user confidence that the substance of interest has been effectively delivered, especially in cases where the delivery of the substance of interest depends on the insertion and dissolution of the microneedles or the coating. The indicator can measure the dissolution of all or part of the microneedles, depending on whether complete or partial dissolution of the microneedles is required to deliver an effective amount of the substance of interest. For example, by measuring complete dissolution, the indicator can signal to the user that the microneedle patch can be removed from the patient's skin. In some cases, it may be useful for the indicator to signal partial dissolution if partial dissolution will be sufficient to provide an effective amount of the substance of interest, or otherwise signal that interaction with the user of the microneedle patch is necessary or desirable.

[0098] Figure 12Exemplary wear time indicator 1000 is shown in the middle. The wear time indicator (WTI) 1000 can provide a visible indication to the user that the microneedle patch has been worn on the patient's skin for a sufficient period of time. In an embodiment, the WTI 1000 includes a dye blister 1002 and a core assembly 1004. The dye blister 1002 can include a pressable housing 1006 that contains a breakable dye reservoir 1008. The pressable housing 1006 can include a substantially flat portion 1012 and a deformable portion 1014, and the dye reservoir 1008 is placed below the deformable portion. In use, a patient or user can press down on the deformable portion 1014 of the pressable housing 1006 with sufficient force to break the dye reservoir 1008 therein. After the dye reservoir 1008 has been broken, the dye within the dye reservoir 1008 can be transferred to the core assembly 1004 through a channel 1016 in the bottom 1010 of the pressable housing 1006 at a controlled rate. That is, the size of the channel 1016 can be selected such that the dye diffuses at a predetermined controlled rate.

[0099] The core assembly 1004 can include a wicking film 1018 that is configured to absorb the dye from the dye blister 1002. The wicking film can be mounted on a backing 1020 and covered by a protective layer 1022. In some embodiments, the backing 1020 itself can be formed of an adhesive material such that the wicking film 1018 can be directly fixed to the adhesive surface of the backing 1020. In other embodiments, the wicking film 1018 is attached to the backing 1020 with additional adhesive (not shown), or the protective layer 1022 effectively holds the wicking film 1018 in place on the backing 1020. The backing layer 1020 can also contain an additional adhesive layer (not shown) on the side opposite the wicking film 1018 to attach the wear time indicator to the microneedle patch, such as the microneedle patch described herein.

[0100] In an embodiment, the wicking film 1018 has a central portion 1024 on which the dye from the dye blister 1002 is initially deposited; and a peripheral portion 1026 along which the dye will travel over a given period of time. In some embodiments, as Figure 12As shown, the central portion 1024 is circular and is located below an opening 1028 of similar size and shape in the protective layer 1022 of the core assembly 1004. When the dye from the dye reservoir 1012 passes through the opening 1028 in the protective layer 1022 and reaches the central portion 1024 of the wicking membrane 1018. When the central portion 1024 becomes saturated with dye, the dye will begin to travel along the peripheral portion 1026 of the wicking membrane 1018 disposed around the central portion 1024 in a spiral configuration. Over time, the dye will travel around the peripheral portion 1026 of the wicking membrane 1018, where the distance the dye has traveled or the portion of the wicking membrane 1018 on which the dye has traveled (i.e., the amount of dye that has been absorbed) corresponds to the amount of time the microneedle patch has been worn. For example, as Figures 13A - 13D shown, the wicking membrane 1018 can be free of dye before the dye reservoir 1012 ruptures ( Figure 13A ), and after the reservoir 1012 ruptures, the dye will cover the central portion 1024 ( Figure 13B ) and a portion of the peripheral portion 1026 ( Figure 13C ). At the end of the specified wear time, the dye will cover the entire peripheral portion ( Figure 13D ).

[0101] The upper portion 1008 of the dye blister 1002 can also include one or more windows 1030 through which one or more regions of the wicking membrane 1018 are visible. The position of the visible region of the wicking membrane 1018 or the window 1030 can depend on the desired wear time of the patch. For example, if the optimal wear time of the patch is 10 minutes, it may take 10 minutes for the dye to be completely absorbed by the wicking membrane 1018. In some embodiments, the dye blister 1002 has a single window 1030 for indicating the final wear time of the microneedle patch, as Figures 13A - 13D shown. In other embodiments, as Figure 12 shown, the dye blister 1002 can have at least one additional window 1030 that is positioned at an intermediate location along the peripheral portion 1026 of the wicking membrane 1018 to indicate a wear time shorter than the total wear time. For example, if the total wear time is 10 minutes, a first window 1030 can be placed at the end of the peripheral portion 1026 of the wicking membrane 1018 to indicate a full 10-minute wear time, and a second window 130 can be placed to indicate a shorter wear time, such as 1 minute, 3 minutes, 5 minutes, etc. In an embodiment, the wear time is from 30 seconds to 10 minutes, preferably 30 seconds, 1 minute, 3 minutes, or 5 minutes.

[0102] Those skilled in the art will readily appreciate modifications and variations of the methods and apparatuses described herein from the foregoing detailed description. Such modifications and variations are intended to fall within the scope of the appended claims.

Claims

1. A microneedle patch, comprising: An array of microneedles; A base substrate having a first side and an opposite rear side, the microneedles extending from the first side; And A force feedback indicator (FFI) attached to the rear side of the base substrate, wherein the FFI includes a base and a button having an upper surface and a side surface, wherein the button is configured to translate within the base from a pre-actuated position to an actuated position, and wherein the side surface is substantially visible in the pre-actuated position and substantially invisible in the actuated position.

2. The microneedle patch according to claim 1, wherein the FFI is configured to further provide a tactile and / or audible confirmation of sufficient force applied to the microneedle patch to effect insertion of the microneedles.

3. The microneedle patch according to claim 1 or 2, wherein the side surface has a color different from that of the upper surface.

4. The microneedle patch according to any one of claims 1 to 3, wherein the side surface has a color different from that of the base.

5. The microneedle patch according to any one of claims 1 to 4, wherein the base has a lateral ring portion and a central cup portion, and a snap dome is disposed between the concave surface of the cup portion and the button.

6. The microneedle patch according to any one of claims 1 to 5, wherein the button further includes at least one latch leg extending from the side surface in a direction away from the upper surface, the latch leg including a lip configured to lock with the base in the actuated position to prevent the button from returning to the pre-actuated position.

7. The microneedle patch according to claim 6, wherein the at least one latch leg includes four latch legs at spaced positions around the button.

8. The microneedle patch according to any one of claims 5 to 7, wherein the lateral ring portion includes a plurality of openings therethrough, the plurality of openings effectively imparting flexibility to the base.

9. The microneedle patch according to any one of claims 1 to 7, further comprising a tape layer including an adhesive face and a handling tab, wherein the tape layer is fixed to the FFI.

10. The microneedle patch according to claim 9, wherein the tape layer includes an orifice through which the central cup portion of the base extends, and the FFI is attached to the rear side of the base substrate on the raised surface of the central cup portion opposite the concave surface.

11. The microneedle patch according to claim 9, wherein the tape layer is fixed to the lateral ring portion on the side opposite the adhesive face, and wherein the adhesive face surrounds the orifice and the microneedle array and is configured to removably adhere to the skin of a patient.

12. The microneedle patch according to any one of claims 1 to 11, wherein the FFI is configured to lock the button into the actuated position when the force applied by a user to the patch to insert the microneedles meets or exceeds a predetermined threshold.

13. The microneedle patch according to claim 12, wherein the button includes a latch configured to lock into the substrate in the actuated position to prevent the button from returning to the pre-actuated position after a predetermined microneedle insertion force is applied to the button.

14. The microneedle patch according to any one of claims 1 to 12, wherein the FFI is configured to lock the button into the actuated position when a force applied by a user to the patch to insert the microneedles effectively displaces the button a predetermined distance into the microneedle patch.

15. The microneedle patch according to any one of claims 1 to 14, further comprising a tape layer including an adhesive face and a handling tab, wherein the FFI is secured to the tape layer.

16. The microneedle patch according to any one of claims 1 to 15, wherein the array of microneedles includes a substance of interest and a water-soluble matrix material in which the substance of interest is dispersed.

17. The microneedle patch according to claim 16, wherein the substance of interest includes an antigen or other active pharmaceutical ingredient.

18. The microneedle patch according to any one of claims 1 to 17, wherein the substrate includes a bistable snap dome disposed between the button and an opposing raised platform on which the microneedle array is mounted.

19. The microneedle patch according to any one of claims 1 to 18, wherein the substrate and button of the FFI include styrene or polystyrene.

20. The microneedle patch according to any one of claims 15 to 19, further comprising a tray releasably adhered to the tape layer, the tray including a recess sized to non-contactingly receive and surround the array of microneedles.

21. The microneedle patch according to any one of claims 1 to 20, further comprising a wear time indicator (WTI) configured to provide a visual indication that the microneedle patch has been worn on a user's skin for a period sufficient to effect dissolution of the microneedles after insertion of the microneedles into the user's skin.

22. The microneedle patch according to claim 21, wherein the WTI includes a dye blister and a core assembly, wherein the dye blister includes a rupturable dye reservoir configured to release dye into the core assembly when a force is applied to the microneedle patch to effect insertion of the microneedles, the position of the dye within the core assembly corresponding to the wear time.

23. The microneedle patch according to any one of claims 1 to 22, further comprising a handling tab directly attached to the lower surface of the substrate.

24. The microneedle patch according to claim 23, wherein the handling tab has a storage position in which the handling tab is folded over the top surface of the button and is capable of being unfolded to use the microneedle patch.

25. The microneedle patch according to claim 24, further comprising a release liner that covers the microneedle array and is releasably adhesively attached to the handling tab such that the release liner also folds over the button and is removable to use the microneedle patch.

26. The microneedle patch according to any one of claims 1 to 25, wherein at least an upper portion of the button in the pre-actuation position is raised above the base, and at least an upper portion of the button in the actuated position is flush with or recessed into the base.

27. The microneedle patch according to any one of claims 1 to 26, wherein the base substrate and the array of microneedles are attached only to the button of the FFI, and wherein the size of the base of the FFI is set such that in the pre-actuation position, the array of microneedles is positioned in an opening recessed in the lower surface of the base of the FFI.

28. The microneedle patch according to claim 26 or 27, wherein: the button of the FFI includes a latch; the housing includes a first latch socket configured to receive the latch and releasably hold the button in the pre-actuation position; and the housing includes a second latch socket configured to receive the latch and non-releasably hold the button in the actuated position.

29. The microneedle patch according to claim 28, the microneedle patch being configured such that: a first minimum force on the button effectively removes the latch from the first latch socket and displaces the button towards the base and starts inserting the microneedles into the tissue surface; and a second minimum force on the button effectively moves the latch into the second latch socket and triggers a tactile and / or audible signal that sufficient force has been applied to the microneedle patch to achieve full insertion of the microneedles into the tissue surface.

30. The microneedle patch according to claim 29, wherein the first minimum force is less than the second minimum force.

31. A microneedle patch packaging system, comprising: at least one microneedle patch according to any one of claims 1 to 30, the at least one microneedle patch having an adhesive surface; and foil or other bag material that adheres to the adhesive surface, wherein the foil or other bag material is folded and sealed to form a sealed bag surrounding the at least one microneedle patch.

32. A microneedle patch packaging unit, comprising: a microneedle patch according to any one of claims 1 to 30, the microneedle patch having a handling tab; a packaging tray having a cavity in which the microneedle patch is placed; and foil or other film attached to the tray to seal the cavity, The packaging system is configured such that when removing the foil or other film from the tray, the handling tab is positioned towards the opening of the cavity to facilitate grasping the handling tab to remove the microneedle patch from the packaging tray.

33. A packaging system comprising a plurality of microneedle patch packaging units in the microneedle patch packaging unit according to claim 32, wherein the edges of the packaging trays of each packaging unit are releasably attached at the edges of at least one other packaging tray of another packaging unit.

34. The packaging system according to claim 33, wherein the releasably attached edges are defined by perforation lines in a shared sheet material.

35. A microneedle patch comprising: An array of dissolvable microneedles; A base substrate having a first side and an opposite rear side, the microneedles extending from the first side; And A wear time indicator (WTI) attached to the rear side of the base substrate and configured to provide a visual indication that the microneedle patch has been worn on the user's skin for a period sufficient to effect dissolution of the microneedles after insertion of the microneedles into the user's skin, the period being the wear time.

36. The microneedle patch according to claim 35, wherein the WTI comprises a dye blister and a core assembly, wherein the dye blister comprises a rupturable dye reservoir configured to release dye into the core assembly when a force is applied to the microneedle patch to effect insertion of the microneedles, the position of the dye within the core assembly corresponding to the wear time.

37. The microneedle patch according to claim 35, wherein the WTI comprises a dye blister and a core assembly, wherein the dye blister comprises a dye reservoir and a pressable outer shell surrounding the dye reservoir, and wherein the wicking assembly comprises a wicking film configured to absorb dye from the dye reservoir.

38. The microneedle patch according to claim 37, wherein the dye reservoir is configured to rupture upon application of the force.

39. The microneedle patch according to claim 37 or 38, wherein the dye blister is configured to allow dye from the dye reservoir to transfer to the wicking film at a predetermined rate to change the color of the wicking film in one or more zones corresponding to the wear time.

40. The microneedle patch according to claim 39, wherein the dye blister comprises at least one window through which the one or more zones of the wicking film are visible.

41. The microneedle patch according to claim 40, the microneedle patch comprising a single window positioned to view only the zone corresponding to the wear time.

42. The microneedle patch according to any one of claims 35 to 41, wherein the wear time is from 30 seconds to 10 minutes, preferably 30 seconds, 1 minute, 3 minutes or 5 minutes.

43. The microneedle patch according to any one of claims 35 to 42, further comprising a force feedback indicator (FFI) located between the WTI and the rear side of the base substrate.

44. The microneedle patch according to claim 43, wherein the FFI is configured to provide tactile, audible, and visual confirmation of sufficient force applied to the microneedle patch to effect insertion of the microneedles.

45. The microneedle patch according to claim 43 or 44, wherein the FFI comprises a base and a button having an upper surface and side surfaces, wherein the button is configured to translate within the base from a pre-actuated position to an actuated position, and wherein the side surfaces are substantially visible in the pre-actuated position and substantially invisible in the actuated position.

46. A microneedle patch, comprising: an array of microneedles; a base substrate having a first side and an opposite rear side, the microneedles extending from the first side; and a force feedback indicator (FFI) comprising a base and a button, wherein the base substrate and the array of microneedles are attached only to the button of the FFI, wherein the button is configured to translate within the base from a pre-actuated position to an actuated position, and wherein the size of the base of the FFI is set such that in the pre-actuated position, the array of microneedles is positioned within an opening recessed in the lower surface of the base of the FFI.

47. The microneedle patch according to claim 46, wherein at least an upper portion of the button in the pre-actuated position is raised above the base, and at least an upper portion of the button in the actuated position is flush with or recessed into the base.

48. The microneedle patch according to claim 46 or 47, wherein the button has an upper surface and side surfaces, wherein the side surfaces are substantially visible in the pre-actuated position and substantially invisible in the actuated position.

49. The microneedle patch according to any one of claims 46 to 48, wherein: the button of the FFI comprises a latch; the housing comprises a first latch socket configured to receive the latch and releasably hold the button in the pre-actuated position; and the housing comprises a second latch socket configured to receive the latch and non-releasably hold the button in the actuated position.

50. The microneedle patch according to claim 49, the microneedle patch being configured such that: a first minimum force on the button effectively removes the latch from the first latch socket and causes the button to shift towards the base and begin inserting the microneedles into the tissue surface; and a second minimum force on the button effectively moves the latch into the second latch socket and triggers a tactile signal and / or an audible signal that sufficient force has been applied to the microneedle patch to effect full insertion of the microneedles into the tissue surface.

51. The microneedle patch according to claim 50, wherein the first minimum force is less than the second minimum force.

52. The microneedle patch according to claim 49, wherein the microneedle patch is configured such that: a first minimum force on the button effectively (i) removes the latch from the first latch socket and displaces the button towards the substrate and starts inserting the microneedles into the tissue surface; and (ii) moves the latch into the second latch socket and triggers a tactile signal and / or an audible signal that sufficient force has been applied to the microneedle patch to achieve complete insertion of the microneedles into the tissue surface.

53. The microneedle patch according to any one of claims 46 to 52, further comprising a wear time indicator (WTI), the WTI being configured to provide a visual indication that the microneedle patch has been worn on the user's skin for a period sufficient to effect dissolution of the microneedles after insertion of the microneedles into the user's skin.

54. The microneedle patch according to any one of claims 46 to 53, further comprising a handling tab directly attached to the lower surface of the substrate.

55. A microneedle patch packaging system, comprising: at least one microneedle patch according to any one of claims 35 to 54, the at least one microneedle patch having an adhesive surface; and foil or other pouch material, the foil or other pouch material adhered to the adhesive surface, wherein the foil or other pouch material is folded and sealed to form a sealed pouch surrounding the at least one microneedle patch in the microneedle patch.

56. A microneedle patch packaging unit, comprising: a microneedle patch according to any one of claims 35 to 54, the microneedle patch having a handling tab; a packaging tray having a cavity, the microneedle patch being disposed in the cavity; and foil or other film attached to the tray to seal the cavity, wherein the packaging system is configured such that when the foil or other film is removed from the tray, the handling tab is positioned towards the opening of the cavity to facilitate grasping the handling tab to remove the microneedle patch from the packaging tray.

57. A packaging system, the packaging system comprising a plurality of microneedle patch packaging units according to claim 56, wherein the edges of the packaging trays of each packaging unit are releasably attached at the edges of at least one other packaging tray of another packaging unit.

58. The packaging system according to claim 57, wherein the releasably attached edges are defined by perforation lines in a shared sheet material.

59. The packaging system according to claim 56, wherein, When the microneedle patch is disposed within the storage tray, the free end of the handling tab is positioned at an angle pointing upwardly towards the tray opening.

60. The packaging system according to claim 56, wherein the packaging tray of the packaging unit is configured to present the free end of the handling tab at an angle pointing upwardly towards the tray opening.

61. A microneedle patch packaging system, comprising: a microneedle patch having an adhesive surface; and foil or other pouch material adhered to the adhesive surface, wherein the foil or other pouch material is folded and sealed to form a sealed pouch surrounding at least one of the microneedle patches in the microneedle patch assembly.

62. A microneedle patch packaging unit, comprising: a microneedle patch having a handling tab; a packaging tray having a cavity in which the microneedle patch is disposed; and a foil or other film attached to the tray to seal the cavity, wherein the packaging system is configured such that when the foil or other film is removed from the tray, the handling tab is positioned towards the opening of the cavity to facilitate gripping the handling tab to remove the microneedle patch from the packaging tray.

63. A packaging system comprising a plurality of microneedle patch packaging units according to claim 62, wherein the edges of the packaging trays of each packaging unit are releasably attached at the edges of at least one other packaging tray of another packaging unit.

64. The packaging system according to claim 63, wherein the releasably attached edges are defined by perforation lines in a shared sheet material.

65. The packaging system according to any one of claims 62 to 64, wherein, When the microneedle patch is disposed within the storage tray, the free end of the handling tab is positioned at an angle pointing upwardly towards the tray opening.

66. The packaging system according to any one of claims 62 to 64, wherein the packaging tray of the packaging unit is configured to present the free end of the handling tab at an angle for handling pointing upwardly towards the tray opening.

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