In the preferred embodiment, a method of making microneedles comprises i) providing a microneedle template (300) having a plurality of microneedles cavities (360) on one surface, ii) preparing a casting solution (320) comprising at least one matrix material and its solvent, iii) subjecting said microneedle template (300) to a vacuum pressure for a length of time to deprive it of air, iv) dispensing the casting solution (320) over the air-deprived microneedle template, v) allowing the casting solution (320) to be drawn into the air-deprived microneedle cavities (360) completely, and vi) allowing the dissolving microneedles to solidify or dry in a controlled environment.

The present invention provides a solution to increase the drug loading capacity and drug delivery precision of dissolving microneedles. These solutions include: (a) increasing the base of the microneedle cavities without substantially changing the microneedle's height and geometry, (b) use of drug suspension and (c) a specific centrifugation order for filling drug and matrix material. In the first preferred embodiment, a microneedle master mould comprising a plurality of microneedles, wherein each of the microneedles further comprising a chamfered base which extends to and adjoins with its neighboring chamfered bases is provided. In the second preferred embodiment, a method of making dissolving microneedles is provided, comprising (a) providing a microneedle template comprising a plurality of microneedle cavities, wherein each of the microneedle cavities further comprising a chamfered base which extends to and adjoins with its neighboring chamfered bases; (b) dispensing a drug suspension in the substrate cavity on the microneedle template; (c) centrifuging the microneedle template which is loaded with a drug suspension, (d) dispensing a matrix material solution in the substrate cavity on the microneedle template; (d) centrifuging the microneedle template loaded with the drug suspension and the matrix material solution; and (e) drying the centrifuged microneedle template in a controlled environment.

An apparatus and method for manufacturing a microneedle are disclosed, which aim to reduce the production costs of microneedle preparation and improve the efficiency and quality of microneedle preparation. The apparatus for manufacturing a microneedle includes a baseplate, an elastomeric female mold, a horizontal movement mechanism, a vertical movement mechanism, a dispenser and a roller mechanism. The elastomeric female mold is disposed on the baseplate and has a surface formed thereon with cavities complementary to needle bodies. The dispenser includes a reservoir for holding a solution for forming the microneedle. The roller mechanism is disposed on the dispenser and includes a roller. In practical use, the roller is driven by the vertical movement mechanism to apply a predetermined value of pressure onto the elastomeric female mold and is then driven by the horizontal movement mechanism to move horizontally on the elastomeric female mold, thereby evacuating air from the cavities and coating the solution dispensed from the reservoir on the elastomeric female mold. In this way, high filling efficiency and good filling quality are achievable.

A device for producing microstructures, particularly microneedles and more particularly microneedle arrays, including a female mold that has, on a top side, at least one in particular conical depressed portion for producing a microstructure. The female mold is, for example, in the form of a silicone cap and is connected to a hollow cylinder in particular via a holding element. A plunger is disposed movably inside the hollow cylinder.

Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject). In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component is associated with a self-actuating component. For example, the self-righting article may comprise a self-actuating component configured, upon exposure to a fluid, to release the tissue interfacing component from the self-righting article. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent (e.g., for delivery to a location internal to a subject).

Disclosed herein are drug delivery devices that can temporally and spatially deliver biologically active agents. An example drug delivery device includes a microneedle array comprising a plurality of microneedles on a surface of a substrate, each microneedle comprising a core comprising a hydrogel and a layer on a surface of the core. Also disclosed are methods of using the drug delivery device, and methods of making the microneedle array that includes a loading device.

A microneedle array has a plurality of microneedles, said microneedles being supported by a substrate. In order to improve the properties of the microneedle array, the substrate is in the form of a grid structure or comprises a grid structure.

A microneedle structure has one or more microneedles (104) projecting from the major surface (102) of a substrate (100). The microneedle has a penetrating tip (106) formed at an intersection between upright surfaces (108) and an inclined surface (110) corresponding to a (1 1 1) crystallographic plane. The microneedle has an expanding portion bounded by a continuation of the upright surfaces (108) and inclined surface (110), and a constant cross-section portion bounded by a continuation of the upright surfaces and a slicing plane (112) extending from an edge (114) of inclined surface (110) towards, and perpendicular to, major surface (102) of the substrate. A width W of inclined surface (110) increases monotonically from penetrating tip (106) to edge (114).

A cryo formulation-based microneedle device for ocular delivery of bioactive therapeutic agents. The microneedle device includes: one or more microneedle patches each including an array of miniaturized needles, wherein each miniaturized needle defining a base end and a tip; and a substrate to which the base end of the array of miniaturized needles is attached or integrated thereto; wherein the microneedle patch is in a cryo status; wherein each of the one or more microneedle patch is adapted to be applied on cornea of an eye, in which the miniaturized needles penetrates into the eye; and wherein the miniaturized needles is further arranged to melt so as to release one or more bioactive therapeutic agents into the eye to achieve a targeted therapeutic effect.

A cryo formulation-based microneedle device for transdermal delivery of bioactive therapeutic agents. The microneedle device includes: one or more microneedle patches each including an array of miniaturized needles, wherein each miniaturized needle defining a base end and a tip; and a substrate to which the base end of the array of miniaturized needles is attached or integrated thereto; wherein the microneedle patch is in a cryo status; wherein each of the one or more microneedle patch is adapted to be applied on a skin surface, in which the miniaturized needles penetrates into skin; wherein the miniaturized needles is further arranged to melt so as to release one or more bioactive therapeutic agents into the skin to achieve a targeted therapeutic effect; and wherein the bioactive therapeutic agents includes protein and/or antigens.