EP4633719A2

EP4633719A2 - Dissolvable needle for ingestible device and methods for manufacturing the same

Info

Publication number: EP4633719A2
Application number: EP23844579.5A
Authority: EP
Inventors: Mark Gebert; Kimberly Kam; Xianyan Wang; Bo Lu; Kristopher Lavery; Joseph DENNIS; Hossein Mostafavi; Kye Lee
Original assignee: Verily Life Sciences LLC
Current assignee: Verily Life Sciences LLC
Priority date: 2022-12-13
Filing date: 2023-12-12
Publication date: 2025-10-22
Also published as: AU2023397991A1; JP2025541233A; WO2024129729A3; WO2024129729A2

Abstract

Introduced here is an ingestible device that is able to deliver medication directly into tissue along the gastrointestinal tract. By designing the needle to partially or fully dissolve following exposure to body fluids, the risk of destruction and obstruction of the gastrointestinal tract can be addressed without requiring a separate retraction system. Dissolution can be achieved by constructing the needle using one or more water-soluble materials - or a combination of one or more water-soluble materials and one or more water-insoluble materials - having known dissolution properties.

Description

DISSOLVABLE NEEDLE FOR INGESTIBLE DEVICE AND METHODS FOR MANUFACTURING THE SAME

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to US Provisional Application No. 63/387,277, titled “Dissolvable Needle for Gastric Injector Device” and filed on December 13, 2022, and US Provisional Application No. 63/476,362, titled “Dissolvable Needle for Ingestible Device and Methods for Manufacturing the Same” and filed on December 20, 2022, each of which is incorporated herein by reference in its entirety.

TECHNICAL FIELD

[0002] Various embodiments concern devices with needles that dissolve or soften after administering medication for safer passage through the gastrointestinal tract.

BACKGROUND

[0003] Pharmaceutical drugs (also called “medications”) are an important part of medicine that rely on the continual advancement of pharmacology to diagnose, cure, treat, or prevent disease. The term “administration” is commonly used to refer to the process by which an individual takes a medication. Medications are commonly designed for enteral administration - where the active ingredients enter the body via the gastrointestinal tract - as little oversight is needed. For example, many of the most common medications are intended to be orally administered, with dosages in tablet form, capsule form, or liquid form.

[0004] Medications having solid unit dosage forms - namely, tablets and capsules - have several benefits. Not only can medications be designed and/or manufactured to be easier to swallow but also to control the release rate of the active ingredients. Although oral consumption of medications in solid unit dosage form is a fairly straightforward route of administration, absorption of the active ingredients is a complex process. [0005] Most medications that are orally administered are thought to be absorbed in the gastrointestinal tract via passive diffusion or active transport. Passive diffusion is widely considered the more important mechanism, and it depends on transfer of the active ingredients across the mucosa to the circulatory system down a concentration gradient. While transfer itself is largely dependent on the size of the concentration gradient, the rate at which transfer occurs can vary tremendously. For example, the transfer rate may depend on the molecular weight and size of the active ingredients, lipid solubility, mucosal blood flow, mucosal surface area, and mucosal permeability, among other variables. For this reason, it can be difficult to predict how quickly an orally administered medication will be absorbed by a living body.

BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Figure 1 includes a cross-sectional view of an example of an ingestible device that is designed to administer medication as it travels through a living body, such as a human body or animal body.

[0007] Figure 2A illustrates the ingestible device prior to ingestion by a living body in its “storage state.”

[0008] Figure 2B illustrates the ingestible device in its “insertion state.”

[0009] Figure 2C illustrates the ingestible device in its “injection state.”

[0010] Figure 2D illustrates the ingestible device in its “passable state” following dissolution of the needle.

[0011] Figures 3A-D include simplified illustrations of the storage state, insertion state, injection state, and passable state, respectively.

[0012] Figure 4 illustrates several possible implementations of a trigger mechanism.

[0013] Figure 5 illustrates how, following ingestion through the mouth, an ingestible device can traverse the esophagus until settling within the stomach.

[0014] Figure 6 includes a high-level illustration of three stages of administration, focusing specifically on the needle.

[0015] Figure 7 includes a flow diagram of a process for manufacturing a dissolvable needle in accordance with a dip coating procedure.

[0016] Figure 8 includes a flow diagram of a process for manufacturing a dissolvable needle in accordance with an extrusion procedure.

[0017] Figure 9 includes a flow diagram of a process for manufacturing a dissolvable needle in accordance with a thermomoulding procedure.

[0018] Figure 10 illustrates how one or more apertures could be formed in the bevel end of a dissolvable needle. [0019] Figure 11 illustrates how one or more indentations could be formed proximate to the bevel end of a dissolvable needle.

[0020] Figure 12 illustrates how after one end of a needle has been beveled, an additional bevel cut may be made to sharpen the bevel end.

[0021] Various embodiments are shown in the drawings for the purpose of illustration. However, those skilled in the art will recognize that alternative embodiments may be employed without departing from the principles of the present disclosure. Accordingly, while certain embodiments are shown in the drawings, the technologies described herein are amenable to various modifications.

DETAILED DESCRIPTION

[0022] Contemporary research has begun exploring how to improve absorption of orally administered medications. For example, several entities have developed digital pills (also called “smart pills”) that are able to electromechanically effect administration of medications following ingestion. Digital pills commonly monitor aspects of the living body and then use this information to influence operations. The nature of this information can vary, however. For example, a digital pill could include a sensor that aids in the determination of location, and medication may not be administered until the output produced by the sensor indicates that the digital pill is located in a predetermined location.

[0023] Despite showing promise, digital pills are still susceptible to error. For example, erroneous output by the sensor could result in the medication being administered in an improper location. As another example, the electromechanical means used to effect administration may malfunction. Further, even if medication is administered in the proper location without issue, absorption still depends on passive diffusion - which, as noted above, can be difficult to predict with accuracy.

[0024] There are also some medications that are simply not suitable for oral administration. These medications may cause gastric irritation or experience inconsistent degradation, or these medications may simply be poorly absorbed within the gastrointestinal tract. Historically, many of these medications have been administered via injection. Such an approach has downsides, however, including the risk of infection from piercing the skin, the requirement for a sterile environment, and the like.

[0025] Introduced here is an ingestible device (also called a “pill”) that is able to address the aforementioned issues by delivering medication directly into tissue along the gastrointestinal tract. As further discussed below, administration of a medication stored in the ingestible device can be achieved by a combination of features.

[0026] First, the ingestible device can include an actuation mechanism that includes (i) a plunging mechanism to which a needle is connected and (ii) a dissolvable trigger mechanism that holds the plunging mechanism in a first position. The term “trigger mechanism” may be used to refer to a mechanical component that physically inhibits movement of the plunging mechanism (and therefore, administration of medication via the needle). Following ingestion, the trigger mechanism may be exposed to body fluids to provoke dissolution. When the trigger mechanism dissolves, the plunging mechanism may move from the first position to a second position, thereby causing the needle to extend into tissue against which the ingestible device is lodged. Such a feature allows the ingestible device to actuate at a predictable time - measured with respect to ingestion - without the need for external stimulus (e.g., a signal originating outside of the body) or internal stimulus (e.g., an output produced by a sensor).

[0027] Second, the needle may also be partially or fully dissolved through exposure to body fluids. Because the medication is delivered along the gastrointestinal tract, a sharpened implement - like a needle - may be needed to penetrate into the submucosal space of the tissue. For a conventional needle made of stainless steel, penetrating into the submucosal space of the tissue would be a trivial task. However, significant damage will occur if a conventional needle were to remain outside in its deployed state as the ingestible device passes through the gastrointestinal tract. Said another way, a conventional needle will cause significant damage if not retracted inside the ingestible device after medication has been administered into the submucosal space of the tissue.

[0028] Historically, ingestible devices have addressed this problem by employing a retraction system that, in operation, retracts the needle - or at least its bevel end - after the medication has been administered. The main drawback is that these conventional retraction systems require additional mechanisms (e.g., for retraction or storage of the needle) that complicate the overall design of the ingestible device. These additional mechanisms not only add cost but also consume space that could be used otherwise (e.g., to store more medication). Moreover, these conventional retraction systems pose a risk of malfunction. If the needle is not properly actuated, then medication cannot be delivered into the submucosal space of the tissue; if the needle is not properly retracted, then damage may occur as the ingestible device passes through the gastrointestinal tract. Simply put, the upsides of these conventional retraction systems rarely outweigh the downsides.

[0029] By designing the needle to partially or fully dissolve following exposure to body fluids, the risk of destruction and obstruction of the gastrointestinal tract can be addressed without requiring a separate retraction system. As further discussed below, dissolution can be achieved by constructing the needle using one or more water-soluble materials - or a combination of one or more water- soluble materials and one or more water-insoluble materials - having known dissolution properties. An example of a dissolution property is dissolution rate. Dissolution properties can be “tuned” using different materials and combinations of materials to meet target performance requirements. Several different approaches to accomplishing this are set forth below.

Terminology

[0030] References in the present disclosure to “an embodiment” or “some embodiments” means that the feature, function, structure, or characteristic being described is included in at least one embodiment. Occurrences of such phrases do not necessarily refer to the same embodiment, nor do they necessarily refer to alternative embodiments that are mutually exclusive of one another.

[0031] The term “based on” is to be construed in an inclusive sense rather than an exclusive sense. That is, in the sense of “including but not limited to.” Thus, the term “based on” is intended to mean “based at least in part on” unless otherwise noted. [0032] The terms “connected,” “coupled,” and variants thereof are intended to include any connection or coupling between two or more elements, either direct or indirect. The connection or coupling can be physical, logical, or a combination thereof. For example, elements may be electrically or communicatively connected to one another despite not sharing a physical connection.

[0033] When used in reference to a list of items, the word “or” is intended to cover all of the following interpretations: any of the items in the list, all of the items in the list, and any combination of items in the list.

[0034] The term “biocompatible” means not harmful to living tissue. Accordingly, the term “biocompatible material” may be used to refer to any material that is not harmful to living tissue, whether its biocompatibility is presently known or not known.

[0035] The term “compressed state” may be used to refer to any state in which a spring is at least partially compressed. Meanwhile, the term “uncompressed state” may be used to refer to any state in which the spring is substantially uncompressed. Those skilled in the art will recognize that whether a spring is fully compressed or partially compressed while constrained - or fully uncompressed or substantially uncompressed while not constrained - may depend on the nature (e.g., design and size) of the spring.

Overview of Ingestible Device

[0036] Figure 1 includes a cross-sectional view of an example of an ingestible device 100 that is designed to administer medication as it travels through a living body, such as a human body or animal body. Note that Figure 1 and other illustrations in the present disclosure are not drawn to scale. Features may be shown significantly enlarged for greater clarity.

[0037] As shown in Figure 1 , the ingestible device 100 can include a capsule 102 with a cylindrical body 104 and atraumatically shaped ends 106A-B. One example of an atraumatically shaped end is a rounded shape that does not cause damage upon contacting living tissue, such as the roughly hemispherical ends shown in Figure 1 . This geometric shape is commonly called a “spherocylinder.” While the ingestible device 100 shown in Figure 1 has roughly hemispherical ends, the ingestible device 100 could have other atraumatically shaped ends in other embodiments. For example, at least one end of the capsule 102 may have a flat portion that can lie against the living tissue. The cylindrical body 104 and atraumatically shaped ends 106A-B may be referred to as the “structural components” of the capsule 102. To avoid contamination of an internal cavity defined by the cylindrical body 104 and/or the atraumatically shaped ends 106A-B, the structural components may be hermetically connected to one another.

[0038] Note that in some embodiments, the cylindrical body 104 is integrally formed with one of the atraumatically shaped ends. For example, the cylindrical body 104 may be integrally formed with atraumatically shaped end 106A, and therefore these structural components may not need to be connected to one another. Instead, components could be installed within these structural components and then atraumatically shaped end 106B may be connected thereto.

[0039] In some embodiments, these structural components comprise the same material. For example, these structural components may comprise plastic, metal, metal alloy, ceramic, polymer, or another biocompatible material, such as naturally derived materials that have comparable mechanical properties to plastics. In other embodiments, these structural components comprise different materials. For example, the atraumatically shaped end 106B through which the needle 108 extends may be comprised of a polymer or metal alloy, while the other atraumatically shaped end 106A and cylindrical body 104 may be comprised of plastic. A large disparity in weight may be helpful in ensuring that the ingestible device 100 is properly aligned with respect to the living tissue into which medication is to be injected, as further discussed below. Moreover, these structural components may have a coating that inhibits exposure to, and degradation from, body fluids. For example, these structural components may be coated with a polymer, a sugar, or a sugar alcohol, via a dip process or spray process, and the coating may improve safety, durability, or operational efficiency of the ingestible device 100. For example, a polymer coating can provide lubrication to aid in passage through the esophagus but may be chemically designed to denature, dissolve, or otherwise degrade in the stomach, yet still remain robust while in the mouth and esophagus and during normal handling.

[0040] Regardless of whether these structural components comprise the same material or different materials, the capsule 102 can be formed in various ways. For example, these structural components could be machined, injection molded, printed (e.g., with a three-dimensional printer), or otherwise formed to accommodate components of the ingestible device 100.

[0041] As shown in Figure 1 , atraumatically shaped end 106A may be largely or entirely empty to provide buoyancy. Here, for example, the inner surface of atraumatically shaped end 106A defines a cavity 1 10 that is vacant. However, relatively lightweight components could be situated within atraumatically shaped end 106A without meaningfully affecting the buoyancy. Such a design may cause the ingestible device 100 to naturally be oriented longitudinally when in body fluids, as further discussed below.

[0042] Meanwhile, a ballast 1 12 may be situated within atraumatically shaped end 106B. The ballast 112 may comprise any material that is able to provide stability. Examples of such materials include metals, metal alloys (e.g., stainless steel, titanium alloys, cobalt-chromium alloys), ceramics (e.g., tungsten carbide), and the like. In Figure 1 , the ballast 112 is connected to the longitudinal segment of the capsule 102 in such a manner that the ballast forms atraumatically shaped end 106B. In such embodiments, the ballast 1 12 is partially or entirely exposed to body fluids following ingestion of the ingestible device 100, and therefore may comprise a biocompatible material. However, in some embodiments, the ballast 1 12 is positioned inside atraumatically shaped end 106B. Because the ballast 1 12 is not exposed to body fluids in such embodiments, the ballast 112 may or may not comprise a biocompatible material.

[0043] As further discussed below, at least one of these structural components could comprise a dissolvable material. Assume, for example, that the capsule 102 includes atraumatically shaped end 106A and cylindrical body 104, but no atraumatically shaped end 106B (and therefore, the ballast 1 12 is exposed to body fluids). Atraumatically shaped end 106A and/or cylindrical body 104 may comprise a material that dissolves following exposure to body fluids for a predetermined amount of time. The material may be a water-soluble polymer or a mixture or combination of soluble and insoluble materials. Examples of soluble materials include polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), dextran, polyethylene oxide (PEG), polyvinyl alcohol (PVA), polyacrylic acid (PAA), hydroxypropyl methylcellulose (HPMC), etc. Examples of insoluble materials include polycarbonate, polystyrene, ethyl cellulose, polylactic acid (PLA), zein, etc. Generally, the predetermined amount of time is sufficiently long that (i) a trigger mechanism 116 of an actuation mechanism 1 14 and (ii) the needle 108 dissolve before the predetermined amount of time elapses. Dissolution of atraumatically shaped end 106A, atraumatically shaped end 106B, or cylindrical body 104 may be helpful in decreasing the size of the ingestible device 100, making it easier for the ingestible device 100 to pass through the gastrointestinal tract after medication has been administered.

[0044] As shown in Figure 1 , atraumatically shaped end 106B can include an aperture 122 through which the needle 108 is able to extend. An actuation mechanism 114 may be responsible for moving the needle 108 from a first position in which its bevel end is located inside the capsule 102 to a second position in which its bevel end is located outside the capsule 102. As further discussed below, the actuation mechanism 114 may include a trigger mechanism 1 16 that, following ingestion, is exposed to body fluids through another aperture 124 in the capsule 102, a plunger mechanism 1 18 that is held in a first position by the trigger mechanism 1 16, and a spring 120 that is held in a compressed state by the plunger mechanism 1 18 while in the first position. The trigger mechanism 116 may comprise a material that dissolves following exposure to body fluids. Following dissolution of the trigger mechanism 1 16, the plunging mechanism 118 may move from the first position to a second position due to the spring 120 transitioning from the compressed state to an uncompressed state. The needle 108 may be connected - either directly or indirectly - to the plunger mechanism 118, and therefore movement of the plunger mechanism 118 may correspond to movement of the needle 108. The term “plunger mechanism” may be used to refer to a mechanical component that causes medication to be administered via rapid repositioning. Approaches to moving the needle 108 are discussed in greater detail below.

[0045] The capsule 102 may have any of a variety of different sizes, such as any of those sizes listed in Table I. Generally, the size of the capsule 102 depends on its contents (e.g., the amount of medication to be stored therein).

Table I: Example sizes of capsules.

[0046] Figures 2A-D illustrate an ingestible device 200 at different stages of administration.

[0047] Figure 2A illustrates the ingestible device 200 prior to ingestion by a living body. At this stage, the ingestible device 200 may be described as being in the “storage state.” As discussed above, the ingestible device 200 may comprise a capsule 202 having a central longitudinal axis 204 (or simply “central axis”) defined therethrough. The capsule 202 may have a substantially cylindrical segment that is interconnected between a pair of rounded ends. In embodiments where the rounded ends are in the form of hemispheres, this shape may be called a “spherocylinder.” Inside the substantially cylindrical segment, a reservoir 206 may store medication - generally in liquid form. The volume of medication that is storable in the reservoir 206 may depend on the size of the capsule 202. Generally, the reservoir 206 is able to store between 25-200 microliters (pL) (and preferably 50-100 pL). As shown in Figure 2A, the reservoir 206 may be partially defined by a seal 208. The bottom surface of the seal 208 - which may define a periphery of the reservoir 206 - may be roughly orthogonal to the central axis 204 while in a first position (also called an “upper position”).

[0048] A needle 210 may be arranged roughly along the central axis 204. The needle 210 may include a hollow shaft 212 with a port 214 defined therein and a bevel end 216. Medication in the reservoir 206 may be able to enter the hollow shaft 212 through the port 214 and exit through the bevel end 216. In Figure 3A, the needle 210 is located in a first position corresponding to a storage state. When the needle 210 is located in the first position, the port 214 may be obscured so as to prevent medication from entering the hollow shaft 212. For example, the port 214 may be covered by the seal 208 through which the needle 210 extends, as shown in Figure 2A.

[0049] In Figures 2B-C, the bevel end 216 has a 45° regular bevel. However, the bevel end 216 could be designed otherwise depending on the tissue into which the needle 210 is to be inserted, the force with which the needle 210 will be inserted into the tissue, etc. Accordingly, the bevel end 216 could have a 22° bevel, 30° bevel, 35° bevel, 45° bevel, etc. In some embodiments, the end 216 may not be beveled at all, instead having a 90° blunt end. Moreover, the bevel end 216 could have a long bevel, medium bevel, short bevel, multi-bevel, or scalpel bevel. Further, the needle 210 could have other forms in some embodiments. For example, the ingestible device 200 could have multiple “microneedles” of relatively small size that are arranged in the form of an array, and the entire microneedle array could be actuated in accordance with the approach described herein. As another example, the ingestible device 200 could include a microneedle (e.g., comprised of epoxy) that has one or more apertures (also called “gills”) along its length through which medication can exit. As another example, the ingestible device could include a barbed projection having one or more apertures through which medication can exit. These apertures may be arranged along its length or near its end (e.g., proximate to the barbs that embed into tissue to inhibit extraction). In such embodiments, the barbed projection may be dissolvable to ensure that the ingestible device 200 is able to readily detach from the tissue into which the medication is administered. Accordingly, the ingestible device 200 may be described as simply having a “projection” through which medication can be discharged into, or near, tissue.

[0050] As noted above, the ingestible device 200 may include an actuation mechanism that, in operation, causes the needle 210 to move along the central axis 204 from the first position in which the bevel end 216 is located inside the capsule 202 to a second position in which the bevel end 216 is located outside the capsule 202. The actuation mechanism can include (i) a trigger mechanism 218, (ii) a plunger mechanism 220, and (iii) a first spring 222. In embodiments where the ballast forms one of the atraumatically shaped ends, the ballast may have an aperture defined therethrough along the central axis 204, so as to accommodate actuation of the needle 210 along the central axis 204.

[0051] Following ingestion, the trigger mechanism 218 may be exposed to body fluids through an aperture (not shown) in the capsule 202. The trigger mechanism 218 can comprise a material that dissolves following exposure to the body fluids for a predetermined amount of time. The material could be a dissolvable polymer, for example. The trigger mechanism 218 could have various forms depending on the design of the actuation mechanism (and more specifically, the plunger mechanism 220 that is held in place by the trigger mechanism 218). In Figure 2A, for example, the trigger mechanism 218 is a pin that extends laterally through an opening (e.g., a hole or slot) in the plunger mechanism 220. The aperture in the capsule 202 through which body fluids are able to contact the trigger mechanism 218 could be located in nearly any position along the periphery of the capsule 202. For example, the aperture may be along the axial axis of the pin, such that the aperture is proximate to one end of the pin. As another example, the aperture may be along a radial axis of the pin, such that the aperture is centrally located along the length of the pin. More than one aperture may be defined through the capsule 202 if the trigger mechanism 218 is to be exposed to greater amounts of body fluid (e.g., to quicken dissolution). For example, the aperture may take the form of a slot that extends radially around at least part of the periphery of the capsule 202.

[0052] Further, the size of the trigger mechanism 218 may be altered to achieve dissolution at a desired rate. Generally, thinner trigger mechanisms will dissolve more quickly than thicker trigger mechanisms. The trigger mechanism 218 may have a diameter between 1 .0-2.5 millimeters. The length of the trigger mechanism 218 may depend on the size of the capsule 202. For example, the trigger mechanism 218 may have a length between 3.0-10.0 millimeters.

[0053] As shown in Figure 2A, the plunger mechanism 220 may initially be held in a first position by the trigger mechanism 218. While in the first position, the plunger mechanism 220 may hold the first spring 222 (also called the “insertion spring”) in a compressed state. The needle 210 can be connected to the plunger mechanism 220, and therefore, movement of the plunger mechanism 220 may correspond to movement of the needle 210 as further discussed below with reference to Figures 2B-C.

[0054] Another spring 224 (called the “second spring” or “injection spring”) can be interconnected between the plunger mechanism 220 and seal 208. When the plunger mechanism 220 in is the first position - shown in Figure 2A - the second spring 224 can be in an uncompressed state or lightly compressed state. When the second spring 224 is in an uncompressed state, the seal 208 will be suspended such that little or no pressure is applied to the medication in the reservoir 206. The tandem nature of the first and second springs 222, 224 may allow the medication to be stored in a low-pressure configuration. It also allows the insertion of the needle 210 into the tissue to be decoupled in time and force from the delivery of the medication into the tissue, allowing for more robust insertion and more reliable timing of medication delivery. This configuration also allows the needle 210 to remain dry as the medication is loaded into the reservoir 206.

[0055] In some embodiments, a mucoadhesive disk 228 is secured along the end of the capsule 202 weighted by the ballast, as shown in Figure 2A. The term “mucoadhesion” is commonly used to refer to the adhesion that occurs between two surfaces, one of which is mucosal in nature. The mucoadhesive disk 228 may comprise any material that is able to improve, at least temporarily, adherence of the ingestible device 200 to the tissue into which medication is to be ejected. The mucoadhesive disk 228 may comprise a polymer, for example, that has hydrophilic groups (e.g., hydroxyl, carboxyl, amide, or sulfate) that attach to the tissue via interactions such as hydrogen bonding, hydrophobic interactions, or electrostatic interactions. For example, the polymer may be coated along the mucoadhesive disk 228, or the mucoadhesive disk 228 may be comprised entirely of the polymer. In some embodiments, the polymer is dissolvable. Dissolution of the polymer may allow the mucoadhesive disk 228 to more readily detach from the tissue. For example, adhesiveness could simply lessen due to dissolution of the polymer, or dissolution of the polymer could result in dissolution of the mucoadhesive disk 228 itself.

[0056] Referring now to Figure 2B, following dissolution of the trigger mechanism 218, the plunging mechanism 220 can move from the first position to a second position in response to the first spring 222 transitioning from the compressed state to an uncompressed state. In Figure 2B, dissolution of the trigger mechanism 218 causes the plunging mechanism 220 to move “downward” along the central axis 204. Because the needle 210 is connected to the plunging mechanism 220, movement of the plunging mechanism 220 can correspond to movement of the needle 210 along the central axis 204. Specifically, the bevel end 216 of the needle 210 can extend through another aperture 226 in the capsule 202. In the event that the ingestible device 200 is located adjacent to tissue, such movement of the needle 210 may result in the bevel end 216 piercing the surface of the tissue. Accordingly, Figure 2B illustrates the ingestible device 200 in its “insertion state.”

[0057] In Figure 2B, the needle 210 is located in a second position corresponding to an insertion state. When the needle 210 is located in the second position, the port 214 may be accessible such that medication can enter the hollow shaft 212. At a high level, the port 214 is located within the periphery of the reservoir 206 while the needle 210 is located in the second position. However, the needle 210 is preferably designed such that the port 214 is located near the “bottom” of the reservoir 206, as shown in Figure 2B. Medication may be able to more easily flow into the hollow shaft 212 when the port 214 is located nearer the “bottom” of the reservoir 206. Moreover, locating the port 214 near the “bottom” of the reservoir 206 will allow more medication to be administered, as the port 214 is less likely to be obscured, for example, by the seal 208 as it moves “downward” along the central axis 204 from the first position (also called the “upper position”) to a second position (also called a “lower position”). The seal 208 is located in the upper position in Figure 2A, while the seal 208 is located in the lower position in Figure 2C.

[0058] As shown in Figure 2B, the second spring 224 can be compressed due to “downward” movement of the plunging mechanism 220 along the central axis 204. This compression is due to the force applied to the bottom surface of the seal 208 by the medication stored in the reservoir 206. At a high level, the medication is sufficiently constrained (and therefore, pressurized) that force is applied against the bottom surface of the seal 208.

[0059] Referring now to Figure 2C, as medication flows into the needle 210 through the port 214 and out of the needle 210 through the bevel end 216, the amount of medication in the reservoir 206 will lessen (and therefore, the force applied against the bottom surface of the seal 208 will also lessen). Accordingly, Figure 2C illustrates the ingestible device 200 in its “injection state.” Over time, the second spring 224 will transition from the compressed state to an uncompressed state. Such movement will “push” the medication through the port 214 into the needle 210. Generally, the second spring 224 is designed such that when the second spring 224 returns to the uncompressed state, the seal 208 is located near the bottom of the reservoir 206, as shown in Figure 20. Said another way, the second spring 224 may be designed - in combination with the seal 208, first spring 222 and plunger mechanism 220 - so that most, if not all, of the medication is administered into tissue through the bevel end 216 of the needle.

[0060] Note that, in operation, the insertion stage and injection stage shown in Figure 2B and Figure 20, respectively, tend to occur in rapid succession. For example, the ingestible device 200 may only be in the insertion stage momentarily (e.g., several dozen or hundred milliseconds), as the second spring 224 rapidly compresses as shown in Figure 2B and then expands as shown in Figure 2C.

[0061] As mentioned above, the needle 210 may comprise a material that dissolves following exposure to body fluids. In operation, the bevel end 216 of the needle 210 may extend into tissue during the insertion stage, and medication may flow through the bevel end 216 of the needle 210 into the tissue during the injection stage. The ingestible device 208 (and more specifically, its actuation mechanism, reservoir 206, seal 208, and needle 210) can be designed so that the medication is mostly, if not entirely, administered over an interval of time having a known length. For example, the interval of time may be several seconds to several minutes. As further discussed below, the needle 210 can be designed such that dissolution occurs after the interval of time has elapsed. Because the bevel end 216 is sharp enough to pierce the tissue, it must be accommodated if the ingestible device 200 will exit the living body by traversing the gastrointestinal tract. Having the needle 210 dissolve eliminates the need for the needle 210 to be retracted back into the capsule 202 in order to ensure safe passage through the gastrointestinal tract. Figure 2D illustrates the ingestible device 200 in its “passable state” following dissolution of the needle 210.

[0062] Note that, in some embodiments, only a portion of the needle 210 may be dissolvable. For example, the bevel end 216 may dissolve, leaving a blunted needle that cannot permeate tissue, and therefore could be passed without complete dissolution. Further, while the needle 210 may be described as “dissolvable,” its constituent materials may not necessarily be water soluble. For example, the needle 210 could be comprised of a water-insoluble material instead of, or in addition to, a water-soluble material, and the water-insoluble material may be biodegradable or biocompatible in the sense that it can be taken up by, or expelled from, the body without issue.

[0063] Figures 3A-D include simplified illustrations of the storage state, insertion state, injection state, and passable state, respectively. For simplicity, only the actuation mechanism - including the trigger mechanism 302, plunger mechanism 304, and first spring 306 - second spring 308, seal 310, and needle 312 are shown with respect to the capsule 300.

[0064] Following ingestion, the trigger mechanism 302 can be exposed to body fluids through an aperture in the capsule 300. The trigger mechanism 302 can hold the plunger mechanism 304 in a first position, and while the plunger mechanism 304 is in the first position, the plunger mechanism 304 may hold the first spring 306 in a compressed state, as shown in Figure 3A. Further, because the needle 312 is connected to the plunger mechanism 304, the trigger mechanism 302 can also hold the needle 312 in a first position - albeit indirectly via the plunger mechanism 304. While the needle 312 is in the first position, (i) the port through which medication enters can be obscured and (ii) the bevel end through which the medication exits can be fully retained within the capsule 300. For example, the port may be centrally located along the length of the needle 312, such that the port is covered by the seal 310. [0065] As mentioned above, the trigger mechanism 302 can be comprised of a material that dissolves following exposure to body fluids. Following dissolution of the trigger mechanism 302, the plunger mechanism 304 can move from the first position to a second position, as shown in Figure 3B. Movement of the plunger mechanism 304 may be caused by the first spring 306 transitioning from the compressed state to an uncompressed state. Such action may cause the bevel end of the needle 312 to extend through an aperture in the capsule 300, as shown in Figure 3B. The stroke length of the needle 312 can depend on various factors, including the length of the needle 312, the length of the first spring 306, the amount of compression of the first spring 306, and the like. However, the length of the stroke during the insertion stage - commonly called the “insertion stroke” - may be between 2-6 millimeters (and preferably 2.5-3.5 millimeters).

[0066] As the plunger mechanism 304 moves toward the second position, the second spring 308 may become more compressed. Said another way, movement of the plunger mechanism 304 may cause the second spring 308 to transition from the uncompressed state to a compressed state. Note that the second spring 308 may not necessarily become fully compressed as shown in Figure 3B, but may instead be partially compressed due to the resistive force applied by the seal 310. Thereafter, the second spring 308 will transition from the compressed state back to the uncompressed state. As shown in Figure 3C, reversion of the second spring 308 to the uncompressed state can cause the seal 310 to move from a first position (Figure 3B) to a second position (Figure 3C). While not shown in detail here, the seal 310 may move through a reservoir 314, “pushing” medication in the reservoir 314 into the needle 312 through a port. The medication can travel through the hollow shaft of the needle 312 and then be ejected through the bevel end of the needle 312.

[0067] In some embodiments, movement of the seal 310 does not cause any further movement of the needle 312. Said another way, the stroke length of the needle 312 may not lengthen during the injection stage in some embodiments. However, in other embodiments, the needle 312 is further extended as the seal 310 moves. This may be caused by further movement of the plunger mechanism 304 as the reservoir is emptied of medication. The length of the stroke during the injection stage - commonly called the “injection stroke” - may be between 1-3 millimeters (and preferably 1 .5-2.0 millimeters). The injection stroke can be optimized based on the target volume of medication to be delivered and the configuration of the reservoir 314. For example, because a capsule of 000 size has a larger cross-sectional area available for the reservoir 314, less stroke may be required to deliver the same volume of medication in comparison to a capsule of 0 size.

[0068] The needle 312 can also be comprised of a material that dissolves, softens, or otherwise denatures following exposure to body fluids to reduce the potential for tissue damage while passing through the gastrointestinal tract. Accordingly, the needle 312 - or at least a portion thereof (e.g., the bevel end) - may dissolve. Generally, the needle 312 is designed or constructed such that sufficient time (e.g., 2-30 minutes, and preferably 5-10 minutes) elapses for administration purposes before dissolution begins. As shown in Figure 3D, dissolution of the needle 312 allows that end of the capsule 300 to become atraumatic once again.

[0069] Figure 4 illustrates several possible implementations of a trigger mechanism 402. Specifically, Figure 4 illustrates a “central design” where the trigger mechanism 402 extends into the plunger mechanism 404 and a “lateral design” where the trigger mechanism 402 runs alongside the plunger mechanism 404. Those skilled in the art will recognize that these implementations are intended to illustrate rather than limit the nature of the trigger mechanism 402.

[0070] In the “central design,” the trigger mechanism 402 can extend into an opening in the plunger mechanism 404. The opening could be a notch as shown in Figure 4, or the opening could be an aperture that extends entirely through the plunger mechanism 404 roughly along a latitudinal axis 408. When held in place by the trigger mechanism 402, the plunger mechanism 404 may be oriented lengthwise roughly along a longitudinal axis 406. As mentioned above, following ingestion, the trigger mechanism 402 may be exposed to body fluids through an aperture in the capsule 400, and upon dissolving, the plunger mechanism 404 may move “downward” along the longitudinal axis 406 such that the bevel end of the needle extends through the capsule 400.

[0071] In the “lateral design,” the trigger mechanism 402 can run alongside the plunger mechanism 404. As shown in Figure 4, the plunger mechanism 404 may be tilted (e.g., by 5-10 degrees with respect to the longitudinal axis 406), such that a latching component 410 engages a structural component 412. The structural component 412 may be partially complementary to the latching component 410, such that movement of the plunging mechanism 404 is inhibited by engagement between those components while the trigger mechanism 402 is in place. Generally, the latching component 410 and structural component 412 are designed to permit a maximum axial translation along the latitudinal axis 408 between 0.1-0.5 millimeters (and preferably about 0.2-0.3 millimeters). The structural component 412 could be affixed to the inner surface of the capsule 400, or the structural component 412 could be part of the capsule 400. For example, the structural component 412 may be representative of the inner surface of the cylindrical body (e.g., cylindrical body 104 of Figure 1 ) or atraumatically shaped end (e.g., atraumatically shaped end 106A of Figure 1 ). At a high level, the trigger mechanism 402 may “pin” the latching component 410 of the plunger mechanism 404 against the structural component 412.

[0072] As shown in Figure 4, the trigger mechanism 402 may tip the plunger mechanism 404 off the longitudinal axis 406, and as the trigger mechanism 402 dissolves, the design of the plunger mechanism 404 (and more specifically, the latching component 410) may allow for self-alignment with the longitudinal axis 406 and release from its “pinned” position. Following dissolution of the trigger mechanism 402, diametric reduction of the structural component 412 may permit actuation of the plunger mechanism 404. The diametric reduction may vary based on the design (e.g., form and dimensions) of the latching component 410. For example, if the latching component 410 has a roughly inverted bell form, then diametric reduction of 0.3-0.7 millimeters may permit actuation. Following dissolution of the trigger mechanism 402, the plunger mechanism 404 may move “downward” along the longitudinal axis 406 and laterally along the latitudinal axis 408 toward the longitudinal axis 406. Accordingly, the plunger mechanism 404 may “straighten out” as it moves “downward.”

[0073] Having a dissolvable trigger mechanism may be an important feature of the ingestible device, as it allows actuation of the needle to be done “passively” in the sense that active actuation (e.g., with a motor) is not necessary. In the “lateral design,” while the trigger mechanism 402 prevents movement of the plunger mechanism 404 prior to dissolution, the trigger mechanism 402 need not be comprised of materials having high strength. Simply put, when the trigger mechanism 402 is positioned alongside the plunger mechanism 404, little material strength is required because this design eliminates dependence on reduction of shear strength. Further, the trigger mechanism 402 may be axi-symmetric with this design, which may ease the manufacturing and assembling processes.

Overview of Passive Locomotion

[0074] Figure 5 illustrates how, following ingestion through the mouth, an ingestible device 500 can traverse the esophagus until settling within the stomach. Once inside the stomach, the ingestible device 500 can naturally situate itself in a longitudinal arrangement (also called the “vertical arrangement”). The ingestible device 500 may have a central axis 502 defined therethrough, and when the ingestible device 500 is in the vertical arrangement, the central axis 502 may be roughly orthogonal to the surface 504 of the tissue into which medication is to be injected.

[0075] As mentioned above, the ingestible device 500 may naturally situate itself in the vertical arrangement along the bottom of the stomach. Generally, this is accomplished by designing a first end (e.g., atraumatically shaped end 106A of Figure 1 ) of the ingestible device 500 to provide buoyancy and a second end (e.g., atraumatically shaped end 106B of Figure 1 ) of the ingestible device 500 to provide ballast. For example, the first end may be largely or entirely empty to provide buoyancy, while the second end may include a high-density component (e.g., comprised of metal, metal alloy, ceramic, etc.) that ensures proper orientation within the stomach.

[0076] In some embodiments, a mucoadhesive is coated along at least the second end of the ingestible device 500. Said another way, the mucoadhesive may be coated along at least an exterior surface of one end of the ingestible device 500. Like the mucoadhesive disk 228 of Figures 2A-D, the mucoadhesive coating can adhere the ingestible device 500 to the tissue to ensure more reliable delivery of the medication contained in the ingestible device 500. The mucoadhesive coating may comprise a polymer, for example, that has hydrophilic groups (e.g., hydroxyl, carboxyl, amide, or sulfate) that attach to the tissue via interactions such as hydrogen bonding, hydrophobic interactions, or electrostatic interactions. Note that in some embodiments, the mucoadhesive coating is constructed or applied such that adhesiveness decreases over time. Assume, for example, that the ingestible device 500 is designed such that its needle dissolves following a first interval of time. It may be desirable for the mucoadhesive coating to lose adhesiveness after - or shortly before - expiration of the first interval of time, so that the ingestible device 500 more readily detaches from the surface 504 of the tissue. Accordingly, the mucoadhesive coating may be designed to dissolve, allowing the ingestible device 500 to complete transit through the gastrointestinal tract intact.

[0077] Such an approach to gastric delivery of medication may be preferable to traditional medications with solid unit dosage forms that rely heavily on passive diffusion. For example, esophageal transit time of the ingestible device 500 may be 5 minutes or less following ingestion and medication may be administered shortly thereafter (e.g., within 5-20 minutes of ingestion, and preferably within 5- 10 minutes of ingestion), while traditional medications may not be absorbed for 120 minutes or more. Consequently, medications can be administered - and take effect - more quickly using the ingestible device introduced here. There is also improved safety margin by administering medication in the stomach, as the thickness of gastric tissue generally averages about 5 millimeters in comparison to intestinal tissue that generally averages about 1 millimeter.

Overview of Needle Dissolution and Approaches to Achieving the Same

A. _ Needle Dissolution

[0078] As mentioned above, any ingestible device that is designed to administer medication directly into tissue along the gastrointestinal tract must include a sharpened implement that is responsible for penetrating into the submucosal space of the tissue. Consider, for example, a scenario in which medication is to be administered into the stomach lining as shown in Figure 5. The ingestible device must be in intimate contact with the stomach lining such that its needle is aligned with the surface, preferably in a roughly orthogonal manner. An actuation mechanism can then cause the needle to be extended into the tissue against which the ingestible device is lodged. Specifically, the bevel end of the needle may be plunged into the tissue following dissolution of a trigger mechanism of the actuation mechanism, as discussed above.

[0079] In order to readily pierce the tissue, the needle must not only have sufficient rigidity along its length but also a sharpened end. The sharpened end is commonly called the “bevel end” because that end of the needle is commonly beveled to create a sharp tip. Because the bevel end is sharp enough to pierce tissue, it must be accommodated if the ingestible device is meant to passively traverse the gastrointestinal tract to exit the body. Simply put, allowing the bevel tip to remain external to the ingestible device may result in significant damage (e.g., torn tissue in the stomach, intestines, colon, etc.).

[0080] Historically, ingestible devices have addressed this problem by employing a retraction system that, in operation, retracts the needle - or at least its bevel end - back inside the capsule after the medication has been administered. There are several drawbacks to employing one of these conventional retraction systems. Notably, these conventional retraction systems require additional mechanisms (e.g., for retraction or storage of the needle) that complicate the overall design of the ingestible device. These additional mechanisms not only add cost but also consume space that could be used otherwise (e.g., to store more medication). Moreover, these conventional retraction systems pose a risk of malfunction. If the needle is not properly actuated, then medication cannot be delivered into the submucosal space of the tissue; if the needle is not properly retracted, then damage may occur as the ingestible device passes through the gastrointestinal tract.

[0081] Rather than employ a retraction system, the ingestible device introduced herein may instead employ a needle that is designed to dissolve, soften, or denature after being exposed to body fluids. As further discussed below, the needle can be designed to dissolve, soften, or denature shortly after medication has been administered, thereby addressing the risk of destruction along the gastrointestinal tract without the need for a separate retraction system.

[0082] Figure 6 includes a high-level illustration of three stages of administration, focusing specifically on the needle 604. Specifically, the three stages roughly correspond to the storage state, injection stage, and passable stage shown in Figures 2A, 2C, and 2D, respectively.

[0083] As can be seen in the first or leftmost illustration, the entire needle 604 may be located inside the capsule 602 when the ingestible device 600 is in the storage state. The needle 604 may remain in this position until actuation is brought about, for example, through dissolution of a trigger mechanism as discussed above with reference to Figure 2B. Accordingly, the needle 602 may remain inside the capsule 602 for an interval of time following ingestion. That interval of time may be based on the dissolution rate of the trigger mechanism.

[0084] As can be seen in the second or middle illustration, the needle 604 can extend through an aperture 606 in the capsule 602 with sufficient force to penetrate tissue against which the ingestible device 600 is lodged. The distance traveled by the needle 604 - also called its “stroke length” - can depend on various factors. Such factors may include the length of the needle 604, design of the actuation mechanism that effects movement of the needle 604, design of the ingestible device 600 (e.g., thickness of the capsule 602 or ballast), characteristics of the tissue into which the needle 604 is to penetrate, and the like. Generally, the stroke is long enough that the bevel end 608 of the needle 604 penetrates between 1-6 millimeters (and preferably 1 .5-3.5 millimeters) into the tissue.

[0085] Note that, in some embodiments, the aperture 606 is left empty. In such embodiments, small amounts of body fluid may enter the capsule 602 through the aperture 606, and therefore, come into contact with the needle 604. The needle 604 may be designed such that meaningful dissolution does not occur until enough time has elapsed following ingestion that medication can be safely delivered into the tissue without issue. For example, the needle 604 may be designed such that dissolution begins roughly 10-40 minutes after ingestion - enough time to ensure that (i) the ingestible device 600 has reached its intended destination, (ii) the needle 604 has plunged into tissue, and (iii) the medication has been injected into the tissue through the needle 604. In other embodiments, the aperture 606 is obscured or blocked to inhibit permeation of body fluid therethrough. For example, a film that serves as a barrier against moisture and/or liquid may be arranged over the aperture 606, and the needle 604 may pierce the film as it extends from the capsule 602. The film could comprise parylene, polyimide, or a combination thereof. As another example, a biocompatible material may be lodged in the aperture 606, and the needle 604 may pierce or dislodge the material as it extends from the capsule 602. Examples of biocompatible materials include some polymers and waxes. Thus, a biocompatible wax-based capsule may be lodged in the aperture 606 to hermetically seal the capsule 602, or at least inhibit exposure of the needle 604 to body fluids. [0086] As can be seen in the third or rightmost illustration, at least a portion of the needle 604 may dissolve, soften, or denature after being exposed to body fluids. In some embodiments, the entire needle 604 - or at least the portion that is exposed to body fluids - partially or fully dissolves. In other embodiments, the needle 604 is designed such that only a predetermined portion (e.g., the bevel end) of the needle 604 partially or fully dissolves. Dissolution enables the ingestible device 600 to passively traverse the gastrointestinal tract with little risk of damage.

[0087] Dissolution may be enabled through the inclusion of at least one water- soluble material in the needle 604. The needle 604 may comprise a single water- soluble material, or the needle 604 may comprise a mixture of multiple water- soluble materials. Examples of water-soluble materials include PEG, PVP, dextran, PEO, PVA, PAA, HPMC, and sugar alcohols such as sorbitol, isomalt, and the like. Accordingly, the needle 604 could be comprised entirely of dextran, or the needle 604 could be comprised entirely of sorbitol, for example. These water-soluble materials exhibit different characteristics, such as dissolution rate (also called “degradation rate”), and therefore selection among these water- soluble materials may be based on a desired performance requirement (also called a “target performance requirement”) of the needle 604.

[0088] Alternatively, the needle 604 may comprise one or more water-soluble materials and one or more water-insoluble materials. As further discussed below, the water-soluble material(s) may be mixed with the water-insoluble material(s) to form a heterogeneous composition (also called a “mixture”). Examples of waterinsoluble materials include biodegradable polymers such as zein, polylactic acid (PLA), polyglycolic acid (PGA), and polylactide-co-glycolide, and non- biodegradable polymers such as ethyl cellulose, polystyrene, polyurethane, silicone, and the like. While mixtures are commonly made of a single water- soluble material and a single water-insoluble material, a mixture could include any number of water-soluble materials and water-insoluble materials. Examples of combinations that may make suitable mixtures include PVP and PEG and zein, PEG and PLA, PVP and ethyl cellulose, and PEG and polystyrene.

[0089] Characteristics of the needle 604 - like its dissolution rate - can be “tuned” by varying not only the water-insoluble materials and/or water-soluble materials used to create the needle 604, but also by varying the ratio of waterinsoluble materials to water-soluble materials. Assume, for example, that a given needle comprises a single water-soluble material (e.g., PEG) and a single waterinsoluble material (e.g., PLA). To slow the dissolution rate, thereby lengthening the interval of time over which the needle 604 is structurally sound, more of the water-insoluble material may be added to the mixture used to create the needle 604. Similarly, to quicken the dissolution rate, thereby lessening the interval of time over which the needle 604 is structurally sound, more of the water-soluble material may be added to the mixture used to create the needle 604. In a mixture, the soluble material should preferably be at least 20 percent by mass and no more than 80 percent by mass (and preferably at least 30 percent by mass and no more than 60 percent by mass).

[0090] The dimensions of the needle 604 can vary depending on the design of the ingestible device 600 as a whole, though the needle 604 normally is in the form of an open cylinder - albeit with a sharpened or beveled end. The needle 604 may have a length between 5-30 millimeters (and preferably 10-25 millimeters). The needle 604 may have an outer diameter (“OD”) between 0.1- 3.5 millimeters and an inner diameter (“ID”) of 0.05-2.70 millimeters. These ranges roughly correspond to conventional needles between 34 gauge and 10 gauge. Several examples of dimensions are provided in Table II.

Table II: Example dimensions of needles.

[0091] Accordingly, the ingestible device 600 may include a capsule 602 with a central axis defined therethrough that includes (i) a first atraumatically shaped end, (ii) a second atraumatically shaped end, and (iii) a cylindrical segment interconnected between the first and second atraumatically shaped ends; a needle 604 comprised of at least a water-soluble material that begins to dissolve following exposure to body fluids for a predetermined amount of time; and an actuation mechanism that, in operation, causes the needle 604 to move along the central axis from a first position in which the bevel end 608 is located inside the capsule 602 to a second position in which the bevel end 608 is located outside the capsule 602. As further discussed above, a ballast may be positioned inside the first atraumatically shaped end of the capsule 602, so as to create a weight differential along the central axis. This may allow the ingestible device 600 to orient itself in a fluid-based environment, such as the stomach. The ballast may have an aperture defined therethrough along the central axis, such that the needle 604 is actuatable through the ballast along the central axis.

B. _ Manufacturing Methodologies

[0092] As mentioned above, dissolution properties of a needle can be “tuned” using different materials and combinations of materials to meet target performance requirements. These dissolution properties could also be influenced by the manner in which the needle is constructed. Several different approaches to constructing dissolvable needles are set forth below. [0093] Figure 7 includes a flow diagram of a process 700 for manufacturing a dissolvable needle in accordance with a dip coating procedure. Initially, a manufacturer can roll a film around a structure having an acerate form to create a rigid scaffold (step 701 ). The film may comprise a water-soluble material that, when exposed to body fluids, begins dissolving within a known amount of time. For example, the film may comprise a cellulosic material. Alternatively, a waterinsoluble thin film may also be applicable. The film is generally thin - having a thickness between 50-150 micrometers, for example - and therefore may be called a “thin film.” In some embodiments the structure is a conventional needle (e.g., a 22 gauge needle, 23 gauge needle, or 25 gauge needle), while in other embodiments the structure is a mandrel that has a needle-like form. Because the film is rolled around and molded onto the structure, and the rigid scaffold may also have a needle-like form. Accordingly, the rigid scaffold may have an open cylindrical form with an outer diameter of 0.1 -3.5 millimeters and an inner diameter of 0.05-2.70 millimeters.

[0094] The manufacturer can dip the rigid scaffold in a solution that includes a second water-soluble material (step 702). Generally, the second water-soluble material included in the solution is different from the first water-soluble material included in the film, though the first and second water-soluble materials could be the same material. Because the second material is water soluble, the solution may not be water based. Instead, the solution may be alcohol based. For example, the solution may be an ethanolic solution that is formed by mixing the second water-soluble material in ethanol. As mentioned above, the dissolvable needle may comprise a water-insoluble material in addition to the second water- soluble material in some embodiments. In such embodiments, the waterinsoluble material may also be included in the ethanolic solution. Accordingly, the manufacturer may prepare the ethanolic solution by mixing the second water- soluble material and water-insoluble material in ethanol.

[0095] Thereafter, the manufacturer can dry the solution on the rigid scaffold to form a coating thereon that comprises the second water-soluble material (step 703). The manufacturer may simply allow the solution to dry on the rigid scaffold for an extended interval of time (e.g., 20 minutes, 30 minutes, 60 minutes), or the manufacturer may dry the solution using a drying system that utilizes heat or air to quicken drying. Additionally or alternatively, the manufacturer could use a chamber with controlled humidity to manage the drying rate in order to form a continuous film with minimal voids.

[0096] The manufacturer can then make a bevel cut along one end of the rigid scaffold, so as to create the dissolvable needle (step 704). In some embodiments, the manufacturer also makes a flat cut (also called a “straight cut”) along the other end of the rigid scaffold to define its “blunt end.” In other embodiments, the blunt end is naturally formed when the film is initially wrapped about the acerate structure. After making the bevel cut, the manufacturer may dip the rigid scaffold into the solution again (step 705). Said another way, the manufacturer may dip the rigid scaffold back into the solution that comprises the second water-insoluble material, in order to create a final coat that acts as a moisture barrier.

[0097] Some materials, such as parylene, tend to be better suited for chemical vapor deposition processes rather than dip coating processes. Films comprising those materials may be applied in a similar matter but instead using in accordance with a chemical vapor deposition process where material is heated to a sufficient temperature to form a vapor that adheres to the dissolvable needle.

[0098] Often, the rigid scaffold is dipped multiple times in order to thicken the coating. Rigidity of the dissolvable needle may correspond to the thickness of the coating. The rigid scaffold has a form that is meant to facilitate a more uniform coating process and reduce the number of “dips” that are needed to create the dissolvable needle. Generally, steps 702-704 are repeated in order to achieve a coating with a thickness between 0.1 -0.3 millimeters (and preferably between 0.12-0.22 millimeters). The thickness may not only be controlled by varying the number of “dips,” but also by varying the concentrations of the solution and the width of the film used to form the rigid scaffold that serves as the “core” of the dissolvable needle.

[0099] Note that each “dip” may not necessarily involve the same solution. Assume, for example, that two solutions are available to the manufacturer, namely, a first solution that includes a water-soluble material mixed with ethanol and a second solution that includes the water-soluble material and a waterinsoluble material mixed with ethanol. In such a scenario, the manufacturer may use the second solution for the first and last dips, and the manufacturer may use the first solution for intervening dips. With this approach, more soluble layers are “sandwiched” between less soluble layers. Alternatively, the manufacturer may use the second solution only for the last dip. To lengthen the time that it takes for dissolution to occur, the manufacturer may perform additional “dips” using the second solution - in effect creating a “shell” that must be dissolved before the more soluble layers are exposed.

[00100] Figure 8 includes a flow diagram of a process 800 for manufacturing a dissolvable needle in accordance with an extrusion procedure. Initially, a manufacturer may prepare a mixture that includes a water-soluble material and a water-insoluble material (step 801 ). Examples of water-soluble materials include PEG, PVP, dextran, PEG, PVA, PAA, HPMC, and sugar alcohols such as sorbitol, isomalt, and the like. Examples of water-insoluble materials include biodegradable polymers such as PLA, PGA, and polylactide-co-glycolide, and non-biodegradable polymers such as ethyl cellulose, polystyrene, polyurethane, silicone, and the like. Examples of combinations that may make suitable mixtures include PVP and PEG and zein, PEG and PLA, PVP and PLA, PVP and ethyl cellulose, PEG and ethyl cellulose, and PEG and polystyrene.

[00101] Thereafter, the manufacturer can extrude the mixture through a movable nozzle to generate a structure having an acerate form (step 802). As shown in Figure 8, the movable nozzle may have a shaping die attached thereto, and the shaping die may include an annular orifice through which the melt is pushed. Generally, the mixture moves through a barrel in molten form, being “pushed” through the annular orifice in the shaping die by a compression mechanism, such as a screw or ram, to form extrudate in the shape of an elongate open cylinder. To create structures having an acerate form, a cutting implement may segment the extrudate on a periodic basis.

[00102] The manufacturer can then subject the structure to a cooling treatment or a pulling treatment (step 803). For example, the manufacturer may subject the structure to a cooling treatment, where the structure is cooled to a predetermined temperature for a predetermined amount of time. Additionally or alternatively, the manufacturer may subject the structure to a pulling treatment, where the structure is pulled at a controlled temperature. Often, the structure is subjected to a cooling treatment and then a pulling treatment after extrusion.

[00103] Then, the manufacturer can make a bevel cut along one end of the structure, so as to create the dissolvable needle (step 804). In some embodiments, the manufacturer also makes a flat cut along the other end of the structure to define its “blunt end.” In other embodiments, the blunt end is naturally formed when the extrudate is segmented by the cutting implement.

[00104] Figure 9 includes a flow diagram of a process 900 for manufacturing a dissolvable needle in accordance with a thermomoulding procedure. Initially, a manufacturer can create a mixture or blend by mixing a water-soluble material and a water-insoluble material until consistency is achieved (step 901 ). Said another way, the manufacturer can create a mixture or blend by mixing the water-soluble material and the water-insoluble material until homogeneity is achieved. Generally, the water-soluble material and water-insoluble material are mixed together. The ratio of the water-soluble material to the water-insoluble material can correspond to the amount of time that structural integrity can be maintained following exposure to body fluids. To lengthen the time that the dissolvable needle maintains its structural integrity, the amount of water-insoluble material can be increased. Conversely, to shorten the time that the dissolvable needle maintains its structural integrity, the amount of water-soluble material can be increased.

[00105] The manufacturer can then either thermally compress or injection mold the mixture or blend into a sheet (step 902). Generally, the sheet has a thickness between 0.5-3.5 millimeters (and preferably 0.5-1 .5 millimeters). Thereafter, the manufacturer can form the sheet into an elongate structure having an open cylindrical form via a thermal reflow process (step 903). As part of the thermal reflow process, the elongate structure may be reheated above the transition temperature of the mixture or blend and the sheet can be reshaped into the elongate structure. Thus, via the thermal reflow process, the sheet can be melted and restructured into hollow tubing.

[00106] Then, the manufacturer can make a bevel cut and a straight cut through the elongate structure, so as to create the dissolvable needle (step 904). Together, these cuts allow the dissolvable needle to have a “blunt end” and a “sharpened end.” In some embodiments the bevel and straight cuts are made by a laser, while in other embodiments the bevel and straight cuts are made by another type of cutting implement.

[00107] In addition to the dip coating, extruding, thermomoulding (also called “melt and reflow”) processes described above with reference to Figures 7, 8, and 9, respectively, a hollow tubing could be formed by casting a warmed mixture that includes a water-soluble material into a mold with a mandrel in the center. After the molten has cooled, the resulting structure can be removed from the mold and the mandrel can be removed from the resulting structure. High- precision cutting can be performed, for example, with a laser, to produce a dissolvable needle from the resulting structure. Specifically, the laser may be used to make a bevel cut, straight cut, or both cuts along opposing ends of the resulting structure.

C. _ Geometric Considerations [00108] In some embodiments, the bevel end of the dissolvable needle is designed to inhibit backward movement. For example, structural design features (or simply “structural features”) may be created, affixed, or otherwise located proximate to the bevel end to ensure that the bevel end cannot be easily removed from tissue (e.g., due to jostling from contents of the stomach). As another example, structural features may be created, affixed, or otherwise located proximate to the bevel end to ensure that medication is more consistently or quickly administered.

[00109] Figure 10 illustrates how one or more apertures 1004 could be formed in the bevel end 1002 of a dissolvable needle 1000. In Figure 10, an array of apertures 1004 are formed circumferentially about the bevel end 1002 in a roughly equidistant manner. However, the apertures 1004 could be formed otherwise. For example, a single ring of apertures 1004 could be formed circumferentially about the bevel end 1002. As another example, multiple lines of apertures 1004 could be formed circumferentially about the bevel end 1002 (e.g., two lines that are spaced roughly 180 degrees apart along opposing sides of the dissolvable needle 1000, or four lines that are spaced roughly 90 degrees apart such that each line is spaced roughly 180 degrees apart from another line).

[00110] Generally, these apertures 1004 are formed using a laser that is able to consistently form apertures having a diameter between 100-500 micrometers (and preferably 150-250 micrometers). However, these apertures 1004 could be formed in other ways. For example, these apertures 1004 could be formed via an etching process. As another example, these apertures 1004 could be “naturally” formed as part of the manufacturing process. Consider, for example, the casting approach described above. Apertures could be “naturally” formed if the mold includes appropriate structural features (e.g., extending from the surface of the mold toward the mandrel) around which the mixture will flow.

[00111] In operation, medication may flow through these apertures 1004 much like how water flows through a showerhead. Such an approach causes medication to be more evenly distributed in the submucosal space of the tissue; rather than a single stream flowing through the tip of the bevel end 1002, medication can instead flow through these apertures 1004 in addition to, or instead of, through the tip of the bevel end 1002.

[00112] Figure 11 illustrates how one or more indentations 1104 could be formed proximate to the bevel end 1 102 of a dissolvable needle 1 100. For example, indentations 1104 may be formed along the outer surface of the dissolvable needle 1100 proximate to the bevel end 1102 in order to inhibit backward movement of the dissolvable needle 1100. These indentations 1104 may be formed (e.g., using a laser) such that the depth is between 100-500 micrometers (and preferably 250-350 micrometers). The depth of these indentations 1104 may depend on the wall thickness of the dissolvable needle 1 100. Generally, these indentations 1104 are formed such that the hollow space inside the dissolvable needle 1 100 is not accessible via these indentations 1104. Said another way, medication generally cannot be administered through these indentations 1104. However, medication could be administered through these indentations in some embodiments, similar to how medication can be administered through the dissolvable needle discussed above with reference to Figure 10.

[00113] Because the bevel end 1102 is cut at an angle, its surface is not perpendicular to the outer surface of the dissolvable needle 1100. This causes one side 1106 of the dissolvable needle 1100 to be longer than the opposing side 1 108. As shown in Figure 1 1 , the indentations 1 104 may be formed along the longer side 1106 to inhibit movement of the bevel end 1102 once embedded in tissue. Additionally or alternatively, the indentations 1104 could be formed along the longer side 1106 further from the bevel end 1 102. Moreover, indentations 1 104 could be formed along the shorter side 1 108 in addition to, or instead of, the longer side 1106. Indentations could be formed anywhere along the exterior surface of the dissolvable needle 1100. [00114] Normally, the indentations 1104 are formed using an angled cut. In Figure 11 , for example, the indentations 1104 are in the form of angled notches. Accordingly, the indentations may not be orthogonal to the exterior surface of the dissolvable needle 1100. Instead, the indentations 1 104 may be roughly orthogonal to the surface of the bevel end 1102 as shown in Figure 1 1 . The indentations 1104 may be formed at different angles depending on the degree to which backward movement should be inhibited.

[00115] Figure 12 illustrates how after one end 1202 of a needle 1200 has been beveled, an additional bevel cut may be made to sharpen the bevel end 1202. Generally, this is done to move the exposed lumen 1204 closer to the sharpened tip 1206 to prevent leakage of medication due to shallow penetration into tissue. To move the exposed lumen closer to the sharpened tip 1206, the additional bevel cut may be less angled than the initial bevel cut. As an example, a manufacturer may initially bevel the end 1202 of the needle 1200 using a bevel cut of 60 degrees and then bevel the sharped end using a bevel cut of 45 degrees. Normally, the initial bevel cut is greater than 45 degrees to create a long, sharp end, while the additional bevel cut is less than, or equal to, 45 degrees.

[00116] Additionally or alternatively, the lumen 1204 could be asymmetrically positioned with respect to the geometric center of the needle 1200. Consider, for example, a scenario where shallow penetration into tissue occurs and only a portion of the sharpened tip 1206 enters the tissue. If the lumen 1204 - shown with dotted lines in the rightmost illustrations of Figure 12 - is positioned along a central axis 1208 that extends longitudinally through the needle 1200, a portion of the lumen 1204 may be exposed. Medication will flow through the exposed portion of the lumen 1204, resulting in less medication being administered into the submucosal space of the tissue. By locating the lumen 1204 nearer the sharpened tip 1206, the likelihood of exposure due to shallow penetration is lessened. As shown in Figure 12, the lumen 1204 may be repositioned to be nearer to the longer side 1210 of the needle 1200. Said another way, the lumen 1204 may be offset from the central axis 1208 toward the longer side 1210, such that the exposed portion of the lumen 1204 is located nearer the sharpened tip 1206.

Remarks

[00117] The foregoing description of various embodiments of the claimed subject matter has been provided for the purposes of illustration and description. It is not intended to be exhaustive or to limit the claimed subject matter to the precise forms disclosed. Many modifications and variations will be apparent to one skilled in the art. Embodiments were chosen and described in order to best describe the principles of the invention and its practical applications, thereby enabling those skilled in the relevant art to understand the claimed subject matter, the various embodiments, and the various modifications that are suited to the particular uses contemplated.

[00118] Although the Detailed Description describes certain embodiments and the best mode contemplated, the technology can be practiced in many ways no matter how detailed the Detailed Description appears. Embodiments can vary considerably in their implementation details, while still being encompassed by the specification. Particular terminology used when describing certain features or aspects of various embodiments should not be taken to imply that the terminology is being redefined herein to be restricted to any specific characteristics, features, or aspects of the technology with which that terminology is associated. In general, the terms used in the following claims should not be construed to limit the technology to the specific embodiments disclosed in the specification, unless those terms are explicitly defined herein. Accordingly, the actual scope of the technology encompasses not only the disclosed embodiments, but also all equivalent ways of practicing or implementing the embodiments.

[00119] The language used in the specification has been principally selected for readability and instructional purposes. It may not have been selected to delineate or circumscribe the subject matter. It is therefore intended that the scope of the technology be limited not by this Detailed Description, but rather by any claims that issue on an application based hereon. Accordingly, the disclosure of various embodiments is intended to be illustrative, but not limiting, of the scope of the technology as set forth in the following claims.

Claims

CLAIMS What is claimed is:

1 . A device designed for ingestion by a living body, the device comprising: a capsule with a central axis defined therethrough that includes -

(i) a first atraumatically shaped end with a mucoadhesive coating applied thereto,

(ii) a second atraumatically shaped end, and

(iii) a cylindrical segment interconnected between the first and second atraumatically shaped ends; a needle that comprises a water-soluble material that begins to dissolve following exposure to body fluids for a predetermined amount of time; and an actuation mechanism that, in operation, causes the needle to move along the central axis from a first position in which a bevel end is located inside the capsule to a second position in which the bevel end is located outside the capsule.

2. The device of claim 1 , wherein the water-soluble material is polyethylene glycol, polyvinylpyrrolidone, dextran, polyethylene oxide, polyvinyl alcohol, polyacrylic acid, hydroxypropyl methylcellulose, sorbitol, or isomalt.

3. The device of claim 1 , wherein the needle further comprises a waterinsoluble material that is mixed with the water-soluble material to form a mixture.

4. The device of claim 3, wherein the water-insoluble material is zein, polylactic acid, polyglycolic acid, polylactide-co-glycolide, ethyl cellulose, polystyrene, polyurethane, or silicone.

5. The device of claim 3, wherein the predetermined amount of time is tunable by increasing or decreasing a ratio of the water-insoluble material to the water-soluble material.

6. The device of claim 1 , further comprising: a ballast that is positioned inside the first atraumatically shaped end of the capsule, so as to create a weight differential along the central axis, wherein the ballast has an aperture defined therethrough along the central axis, such that the needle is actuatable through the ballast along the central axis.

7. A method for manufacturing a dissolvable needle, the method comprising: rolling a film around a structure having an acerate form to form a rigid scaffold; dipping the rigid scaffold in an ethanolic solution that comprises a water- soluble material; drying the ethanolic solution on the rigid scaffold to form a coating thereon that comprises the water-soluble material; and making a bevel cut along an end of the rigid scaffold, so as to create the dissolvable needle.

8. The method of claim 7, wherein the film has a thickness between 50-150 micrometers.

9. The method of claim 7, wherein the film comprises a second water-soluble material that is different from the water-soluble material included in the ethanolic solution.

10. The method of claim 9, wherein the second water-soluble material is a cellulosic material.

1 1 . The method of claim 7, further comprising: preparing the ethanolic emulsion by mixing the second water-soluble material and a water-insoluble material in ethanol.

12. The method of claim 7, further comprising: after making the bevel cut along the end of the rigid scaffold, dipping the rigid scaffold in the ethanolic solution that comprises the water-soluble material.

13. The method of claim 7, wherein said dipping and said drying are performed, in sequence, multiple times to increase thickness of the coating.

14. The method of claim 7, wherein the rigid scaffold has open cylindrical form with an outer diameter of 0.1-3.5 millimeters and an inner diameter of 0.05-2.70 millimeters.

15. A method for manufacturing a dissolvable needle, the method comprising: extruding a mixture that includes a water-soluble material and a waterinsoluble material through a movable nozzle to generate a structure have an acerate form; subjecting the structure to a cooling treatment or a pulling treatment; and making a bevel cut along an end of the structure, so as to create the dissolvable needle.

16. The method of claim 15, wherein the movable nozzle has an annular orifice through which molten mixture is pushed.

17. The method of claim 15, wherein the water-soluble material is polyethylene glycol, polyvinylpyrrolidone, dextran, polyethylene oxide, sorbitol, or isomalt.

18. The method of claim 15, wherein the water-insoluble material is zein, polylactic acid, polyglycolic acid, polylactide-co-glycolide, ethyl cellulose, polystyrene, polyurethane, or silicone.

19. A method for manufacturing a dissolvable needle, the method comprising: thermally compressing or molding a mixture that includes a water-soluble material and a water-insoluble material into a sheet; forming the sheet into an elongate structure having an open cylindrical form via a thermal reflow process; and making a bevel cut and a straight cut through the elongate structure, so as to create the dissolvable needle.

20. The method of claim 19, further comprising: creating the mixture by mixing the water-soluble material and the waterinsoluble material until consistency is achieved.

21 . The method of claim 19, wherein a ratio of the water-soluble material to the water-insoluble material corresponds to an amount of time that structural integrity can be maintained following exposure to body fluids.

22. The method of claim 19, wherein the bevel and straight cuts are made by a laser.

23. The method of claim 19, wherein as part of the thermal reflow process, the elongate structure is reheated above a transition temperature of the mixture and the sheet is reshaped into the elongate structure.