Oral dosage forms for sustained drug release

Abstract

[0003] Described herein are extended-release capsules for the extended delivery of drugs to patients in ingestible capsules, and systems and methods for manufacturing the same. The extended-release capsules include a buoyant compartment that suspends the capsule and a drug compartment with an opening for releasing the drug at a predetermined rate. The capsules are enteric-coated or coated with an enteric coating and float in gastric fluid for a controllable period of time. At the end of this period, the coating dissolves, causing the capsule to fragment and sink into the gastric fluid.

Description

[Technical field]

[0001] (Reference to Related Application) This application claims the benefit of and priority to U.S. Provisional Application No. 62 / 984,067, filed March 2, 2020. The entire contents of the provisional application are incorporated herein by reference for all purposes. [Background technology]

[0002] Typically, orally administered drug dosages include liquids or powders administered as compressed tablets, coated tablets, or gelatin capsules containing a single dose of the selected drug. Administration regimens often require a planned schedule of multiple doses over one or several days. Controlled release dosage forms involve extended delivery of a drug formulation at a predetermined rate to maintain a constant or desired drug concentration for a specific period of time. A typical sustained release drug contains an active ingredient embedded in a matrix of insoluble material, from which the drug must escape before it can be absorbed into the patient's body. Most sustained release products are designed to steadily release the active ingredient for up to several days, but cannot persist in the gastric environment for more than a few days due to the peristaltic action of the intestine that moves the dose out of the stomach. Summary of the Invention [Means for solving the problem]

[0003] (Brief summary) An extended release drug system for releasing an active ingredient over a period of time in a patient's stomach. Although the description is written with reference to a drug, the disclosure is intended to cover medicines, nutraceuticals, medicinal products, supplements, and other consumables. Although reference is made throughout to a drug being released from a capsule, the description is intended to cover any releasable agent from the capsule. As used herein, a releasable agent refers to a drug, medicine, nutraceutical, medicinal product, supplement, and / or other consumable that can be released and can affect a property within the body environment upon release. One general embodiment includes an extended release drug capsule including a first portion having a buoyant chamber and a first coupling mechanism, the buoyant chamber regulating the buoyancy of the capsule in gastric fluid. The extended release drug capsule also includes a drug chamber defining an interior for holding at least one drug, and a second portion having at least one opening in the interior through which the at least one drug is releasable and a second coupling mechanism. The second coupling mechanism is configured to interface with the first coupling mechanism to secure the first portion to the second portion and completely enclose the drug chamber. The extended release drug system is also configured to contain and release one or more drugs mixed with excipients to improve the compaction, dispersion, dissolution, or other such properties of the one or more drugs. The extended release drug system also includes an outer layer comprising a coating disposed on at least one of the first portion or the second portion of the capsule. Other embodiments of this aspect include corresponding structures capable of performing the actions described above.

[0004] Implementations of the extended release drug capsule may include one or more of the following features: The buoyant chamber may include a hollow chamber filled with a gas, typically atmospheric air. In some examples, the buoyant chamber may include a vacuum or partial vacuum. The buoyant chamber may be filled with a porous material that is less dense than the surrounding gastric fluid, for example, a 10 or 20 percent fill created with a three-dimensional (3D) printer configured to create the extended release drug capsule. The buoyant chamber may also include a wall made of a porous material that is less dense than the surrounding gastric fluid and filled with gas. The porous material may have pores that are too small for gastric fluid to enter the buoyant chamber. The extended release drug capsule may include a third compartment having at least a second drug therein. At least one of the dimensions, configuration, or location of the at least one opening may be adjusted based on the physical properties of the at least one drug. The physical characteristic of the at least one drug is at least one of viscosity, density, solubility, absorption rate, caking potential, force to compress the at least one drug into the drug chamber, or hygroscopicity.

[0005] The capsule may further include at least a second opening through which the at least one drug is released. The capsule may be formed of a gastric fluid soluble material. The capsule may be formed of polyvinyl alcohol, or hydroxypropyl methylcellulose, analogs thereof, or combinations of other polymers. The outer layer may be an enteric coating. The at least one drug may be releasable through the at least one opening for at least three consecutive days before the capsule disintegrates in gastric fluid. The buoyant chamber may include a liquid-tight chamber. The liquid-tight chamber may contain a gas. The liquid-tight chamber may contain a biocompatible foam that dissolves in gastric fluid. The buoyant chamber may include a material that is less dense than gastric fluid.

[0006] The outer layer may dissolve in gastric fluid over a period of at least three days. The capsule may be soluble in gastric fluid and may be configured to degrade in gastric fluid after the outer layer dissolves. The outer layer may include a third portion sealing at least one opening of the capsule and a fourth portion covering at least one portion of the capsule, and a dissolution rate of the third portion of the outer layer may be greater than a dissolution rate of the fourth portion. The outer layer may include a third portion sealing at least one opening of the capsule and a fourth portion covering at least a portion of the capsule, and a thickness of the fourth portion may be greater than a thickness of the third portion of the outer layer. The outer layer may cover an outer surface of the first portion and the second portion. The outer layer may coat the first and second connecting mechanisms, and the first and second portions are separable in response to the outer layer dissolving in gastric fluid. The first and second connecting mechanisms may be coupled with a friction fit. The first and second connecting mechanisms may be coupled with a snap fit. The first and second coupling mechanisms can be secured together with an adhesive or a fastening compound. The opening can be on a first side of the capsule opposite the buoyant chamber. The first and second portions can be connected by a living hinge.

[0007] One general aspect includes a method including determining a drug volume for loading a drug into a capsule for treatment of a patient, and determining a buoyant volume of the capsule to provide buoyancy to the capsule. The method also includes determining a capsule size based on the drug volume and the buoyant volume. The method further includes determining a configuration of one or more openings based on at least one physical property of the drug or a drug release rate, the configuration including at least one of a number or at least one size of the one or more openings. The method further includes creating a capsule design having an air compartment, a drug compartment, and at least one release outlet based on the drug volume, the air compartment volume, the one or more openings, and the size of the one or more openings. The method also includes creating manufacturing instructions for a manufacturing system to manufacture the capsule based on the capsule design. Other embodiments of this aspect include corresponding computer systems, devices, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the method.

[0008] The implementation of the method may include one or more of the following features: The air compartment volume may be between 35 and 45 percent of the total volume of the capsule. The method may further include determining a thickness of the outer layer based at least in part on the drug release rate, and the manufacturing instructions include instructions for applying the outer coating to the capsule. The drug amount may be determined based on the drug release rate. The drug volume may be determined based on a physical property of the drug, such as at least one of viscosity, density, solubility, absorption rate, caking potential, compression force of at least one drug, reactivity, or hygroscopicity. The method may further include determining a drug release rate based on a patient's treatment profile. The drug volume may be determined based on the compression force and the drug release rate. Additionally, the method may include the presence of one or more excipients or inactive agents, mixed with the active ingredient for purposes of bulk filling, reducing compaction, reducing particle agglomeration, or improving the dissolution profile. The implementation of the described technology may include hardware, methods or processes, or computer software on a computer accessible medium.

[0009] Another general aspect includes a method of manufacturing a capsule, including receiving manufacturing instructions based on a capsule design, the capsule design including a first portion including a buoyant chamber and a first coupling mechanism and a second portion including a drug chamber, the drug chamber defining an opening providing a conduit between an exterior and an interior of the drug chamber. The capsule design also includes a second coupling mechanism configured to interface with the first coupling mechanism to secure the first portion to the second portion and fully encompass the drug chamber. The manufacturing method also includes using a manufacturing system to manufacture an extended release capsule formed of a gastric acid soluble material based on the manufacturing instructions. Other embodiments of this aspect include corresponding computer systems, devices, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the method.

[0010] The implementation of the method may include one or more of the following features: The manufacturing system may be at least one of a three-dimensional printer using filaments of gastric acid soluble material, an injection molding system, a computer numerical control system, a casting system, an extrusion-based molding system, a powder deposition-based molding system, a selective laser-based molding system, a stereolithography-based molding system, or a vacuum molding system. The implementation of the described technology may include hardware, a method or process, or computer software on a computer-accessible medium. The extension of the implementation may include the transfer of the method to a capsule filling machine of the 3D printed method to scale up the volume of a particular composition of capsule material, filling material, and active ingredient. [Brief description of the drawings]

[0011] [Figure 1] 1 illustrates components of a capsule for extended drug release with release openings on both sides of the capsule, according to at least some embodiments. [Diagram 2] 1 illustrates a component of a capsule for extended drug release having a release opening on one side of the capsule, according to at least some embodiments. [Diagram 3] 1 illustrates components of a capsule for extended drug release having snap closures to secure the components together, according to at least some embodiments. [Figure 4] 1 illustrates components of a capsule for extended drug release having a friction fit to secure the components together, according to at least some embodiments. [Figure 5A] 1 illustrates exemplary stages of drug release in a patient's stomach over an extended period of time, according to at least some embodiments. [Figure 5B] 1 illustrates exemplary stages of drug release in a patient's stomach over an extended period of time, according to at least some embodiments. [Figure 5C] 1 illustrates exemplary stages of drug release in a patient's stomach over an extended period of time, according to at least some embodiments. [Figure 5D] 1 illustrates exemplary stages of drug release in a patient's stomach over an extended period of time, according to at least some embodiments. [Figure 5E] 1 illustrates exemplary stages of drug release in a patient's stomach over an extended period of time, according to at least some embodiments. [Figure 6A] 1 shows a graph of cumulative drug release over time for various capsule designs, according to at least some embodiments. [Figure 6B] 1 shows a graph of cumulative drug release over time for various capsule designs, according to at least some embodiments. [Figure 6C] 1 shows a graph of cumulative drug release over time for various capsule designs, according to at least some embodiments. [Figure 6D] 1 shows a graph of cumulative drug release over time for various capsule designs, according to at least some embodiments. [Figure 7] 1 depicts a simplified flowchart illustrating a process for determining a capsule design for extended drug release, according to at least some embodiments. [Figure 8] 1 depicts a simplified flowchart illustrating a process for creating manufacturing instructions for capsules for extended drug release, according to at least some embodiments. [Figure 9] 1 illustrates an exemplary schematic architecture for implementing techniques relating to creating instructions for manufacturing a capsule for extended drug release, according to at least some embodiments. [Figure 10] 1 illustrates an example computing device for implementing the methods described herein, according to at least some embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] (Detailed Description) Examples are described herein in the context of sustained and extended release capsules for drug release in an orally ingested pill capsule for the treatment of a patient. Although the description is described with reference to drugs, the disclosure is intended to cover medicines, nutraceuticals, pharmaceutical products, supplements, and other consumables. Although reference is made throughout to drugs being released from capsules, the description is intended to cover any releasable agent being released from a capsule. As used herein, a releasable agent refers to a drug, medicine, nutraceutical, pharmaceutical product, supplement, and / or other consumable that can be released and that can affect a property within the body environment when released. Those skilled in the art will appreciate that the following description is merely illustrative and is not intended to be limiting in any way. Reference will now be made in detail to the implementation of the examples illustrated in the accompanying drawings. The same reference labels are used throughout the drawings and the following description to refer to the same or similar items.

[0013] For clarity, not all of the routine features of the examples described herein are shown and described, and it should be understood, of course, that in developing any such actual implementation, many implementation-specific decisions must be made to achieve the developer's particular goals, such as compliance with application and business-related constraints, and that these particular goals will vary from implementation to implementation and from developer to developer.

[0014] Typically, oral drug treatments are delivered in compressed tablets or encapsulated in gelatin capsules. To increase residence time in a patient's stomach, approaches include expanding, unfolding, attaching, and floating mechanisms, each of which has drawbacks and limitations, particularly residence times greater than 24 hours are typically unknown, and some previous methods introduce factors that increase the risk of gastric obstruction. As used herein, drug or active ingredient can include pharmaceutical products, medicines, natural products, dietary supplements, supplements, and complementary health products.

[0015] In comparison, the extended release drug capsules described herein extend the release window and profile of the active ingredient or drug treatment over a time scale longer than the typical physiological gastrointestinal transit time, which is typically about 8 hours for orally ingested capsules. Extended release drug as used herein is intended to cover mechanisms and delivery systems for drug delivery over a period of more than 8 hours, including periods of 3 days to 8 days, and in some instances, the extended release drug capsule period can extend to 30 days and beyond. The capsules described herein can release over a time frame of 3 days to 10 days or more. The capsules described below also include mechanisms for the capsule to break down or fragment into small pieces for passage through the gastrointestinal tract after the drug is fully released. The capsules can reduce the variability of the release rate of the drug, for example, maintaining the release rate of the drug at a zero-order release rate, because the capsule floats in the gastric fluid, and can therefore remain in the patient's stomach by maintaining floating or neutral buoyancy in the patient's stomach. Additionally, capsules may increase patient acceptance due to the familiarity and ease of administration of capsules compared to transdermal drug delivery systems or implantable systems that can provide drug in a similar time frame.

[0016] The embodiments of the present disclosure are directed, inter alia, to an extended release drug capsule having a buoyant compartment and a drug compartment. The buoyant compartment provides buoyancy to the capsule and increases the residence time of the capsule in the stomach. The drug compartment releases the active ingredient from one or more openings at a controlled rate. The capsule is formed of a material that disintegrates in gastric juices, such as polyvinyl alcohol or hydroxypropyl methylcellulose, their analogs, or combinations of other polymers. The capsule may also be enteric in nature or may be a composite of various polymers, such as hydroxypropyl methylcellulose acetate succinate or polymethyl methacrylate, and may be designed to resist or prevent dissolution or fragmentation of the capsule for the required time (3-10 days, or longer). The capsule may be partially or fully coated with an enteric coating to resist or prevent dissolution or fragmentation of the capsule until the enteric coating dissipates. The drug may be released continuously or in pulses at intervals. When the drug is used, the enteric coating and capsule break down into small pieces that pass through the patient's gastrointestinal system.

[0017] The embodiments of the present disclosure are further directed to methods and systems for manufacturing extended release drug capsules. These methods may include receiving therapeutic profile information and drug characteristic information and, based on the information, designing a capsule that will have a long (days) residence in the patient's stomach. The methods include determining the capsule volume, the volume of the buoyant components, and the size, number of the release openings, as well as the placement and addition of excipients to improve the compression, dispersion, dissolution, and cohesion properties of the drug. Systems for manufacturing capsules are also disclosed, including custom manufacturing and mass production techniques including 3D printing, vacuum forming, machining, injection molding, and the like.

[0018] 1 illustrates components of a capsule 100 for extended drug release having a release opening 114 on either side of the capsule 100, according to at least some embodiments. The capsule 100 includes a first portion 102 and a second portion 104 that combine to form the capsule 100. Although the capsule 100 is depicted as having a first portion 102 and a second portion 104, other configurations are envisioned that may include three or more components.

[0019] The first portion 102 may be formed from materials that are generally regarded as safe (GRAS), based on the definition provided by the United States Food and Drug Administration (USFDA). GRAS materials may include biocompatible and biodegradable polymers and products. As an example, polyvinyl alcohol (PVA) or any of its derivatives may be used to form the first portion 102. In some examples, the materials may include polyethylene glycol (PEG), hydroxypropyl methylcellulose acetate succinate (HPMCAS), a mixture of polylactic acid and PEG, and other GRAS materials that are compatible with the manufacturing method. The material must be easily digested and degraded in the patient's gastric juices. In some examples, the first portion 102 is formed from many small components bonded or fused together by a material such as PVA, and when the PVA degrades, the small components break away from each other and fragment into small pieces that can be easily passed by the patient.

[0020] The first portion 102 has a semi-elliptical solid shape such that when combined with the second portion 104 it forms an elliptical solid shape. The elliptical solid shape is familiar to the patient and easy to swallow when administered. Although shown as an elliptical solid, other shapes are within the scope of the present disclosure, such as a cylinder or other such geometric solid or variations thereof. Protruding from the semi-elliptical solid is an interface 106, shown as a rectangular solid, which further defines the shape of the first component 102. An interface edge 110 defines an edge of the interface 106 and provides a vertical surface that is generally adjacent to a surface of the second portion 104 when assembled together at the interface 106. The first portion 102 encompasses a buoyant chamber 108 that provides buoyancy to the capsule 100 when assembled to cause the capsule 100 to float within the gastric fluids of the patient's stomach.

[0021] The buoyant chamber 108 may include a buoyant material or may include a fluid-tight void, such as to hold a gas or keep out a liquid. In some examples, the buoyant chamber may be filled with air, nitrogen gas, oxygen, helium, or other such gas that provides buoyancy to the capsule 100. When the buoyant chamber 100 is compromised at the end of treatment, the gas may be released or displaced by gastric fluids, causing the capsule to lose buoyancy and sink into the gastric fluids, where it may further degrade and be expelled from the patient. In some examples, the buoyant chamber may include a flotation element, such as a foam, or other such structure that is less dense than the gastric fluids and provides buoyancy for the capsule 100. By way of example, a PVA foam may be included in or on the first portion 102.

[0022] The foam may slowly degrade due to interaction with gastric fluids and eventually lose buoyancy at the end of treatment. In such instances, the buoyant chamber 108 need not be a sealed chamber, but may include a buoyant device connected to the first portion 102. In some instances, additional buoyant chambers 108 may be added to the capsule 100, for example, a buoyant chamber 108 may be provided in each of the first portion 102 and the second portion 104 with a chamber for an active ingredient between or adjacent to the buoyant chambers 108. It will be understood that other shapes and layouts of the components of the capsule 100 are intended to be encompassed by this description and would be understood by one of ordinary skill in the art.

[0023] The second portion 104 may be formed of the same material as the first portion 102, or in some instances, may be formed of a different material. For example, the first portion may be formed of PVA, which degrades or dissolves in gastric fluid, while the second portion 104 may be formed of a non-gastric fluid soluble material. If the buoyant chamber 108 is compromised, the capsule 100 may sink even though the second portion 104 is intact. In some instances, the first portion 102 and the second portion 104 are formed of the same material, which degrades in gastric fluid. The second portion 104 may include multiple chambers for holding multiple different drugs within the capsule 100. In some instances, the second portion 104 may be divided lengthwise by a partition having an opening 114 that provides access to each of the divided chambers. In some instances, multiple drugs may be mixed together or compressed into the second portion 104 in layered layers. For example, a first drug may be loaded into the second portion 104 such that the opening 114 closest to the end of the second portion 104 allows for release of the first drug, while the second opening 114 allows for release of the second drug, with the second drug loaded on or adjacent to the first drug.

[0024] The second portion 104 also has a semi-elliptical solid shape, but is open to the environment through the openings 114 and the interface 112. The interface 112 provides a connection for securing the interface 106 and the interface edge 110 to form the capsule 100. The openings 114 are provided on the top and bottom surfaces of the second portion 114 and provide a drug release conduit to the patient's gastric fluids. The openings 114 are shown in a row, but may be arranged in other orientations or configurations. Additionally, while three openings 114 are shown on each side, the number of openings 114 can be increased or decreased with more openings providing greater access and faster drug release rates depending on the drug release rate. There may be openings 114 at an end of the second portion 104, such as the end opposite the interface 112. The openings 114 are shown as circular openings, but other shapes are contemplated, including geometric and irregular shapes.

[0025] The second portion 104 can be filled or loaded with a drug for the treatment of the patient. The drug can be a powder, solid, liquid, or any other suitable form. The drug can be compressed in the second portion 104 to ensure that the first portion 102 and the second portion 104 fit together, as well as to vary the drug release rate through the opening 114. For example, a higher compression force results in a lower release rate, since gastric fluid cannot penetrate tightly packed drug and can only contact the portion of the loaded drug adjacent to the opening 114.

[0026] The interface 106 and the interface 112 bond together with a friction fit to form the capsule 100. In some examples, the interface 106 may have a fastening feature, such as a snap element or a deformation element, to hold the first portion 102 and the second portion 104 together. In some examples, the interface 106 may include an adhesive or other material to provide additional retention between the first portion 102 and the second portion 104.

[0027] When assembled, capsule 100 has an elliptical solid shape with a buoyant chamber 108 at one end of the elliptical shape and an opening 114 at the opposite end of the elliptical shape. When in a fluid, such as gastric fluid, buoyant chamber 108 causes the end of capsule 100 having first portion 102 to float while second portion 104 is submerged. Opening 114, which is submerged, allows for drug release into the gastric fluid.

[0028] In some examples, the capsule 100 may have one or more dimensions, such as a length, width, or diameter, that are larger than the dimensions of the intestine. A dimension larger than the intestine may help ensure that the capsule 100 does not pass out of the stomach until it is fragmented into multiple pieces. Additionally, the capsule 100 may have a size or dimension smaller than the esophagus so that it can be easily swallowed by the patient. The capsule 100 may have a length from a few millimeters, such as 8 millimeters, to a few centimeters, such as 2 centimeters. Similarly, the width and thickness may be within a range of a few millimeters to a few centimeters. The width may range from 3 millimeters to 15 millimeters, and the thickness may range from 3 millimeters to 15 millimeters, or alternatively, from 5 millimeters to 10 millimeters. The opening 114 may have a diameter or effective diameter in the range of 1 to 2 millimeters.

[0029] The capsule 100 may be coated with an enteric coating that prevents the capsule 100 from dissolving or disintegrating in gastric fluids until the enteric coating disintegrates. In some examples, the capsule 100 itself may be formed from an enteric composite material that disintegrates slowly over a period of 3 to 10 days before the capsule 100 degrades or disintegrates. The enteric coating may be any suitable material that is resistant to the digestive action of gastric fluids. The enteric coating may be applied at a thickness that depends on the residence time in the stomach. For example, for a capsule 100 with an intended residence time of 8 to 10 days, the coating will be thicker than for a capsule 100 with an intended residence time of 3 to 4 days. The enteric coating may include, by way of example, EUDRAGIT™ L100 or a solution containing same. In some examples, the enteric coating may include hydroxypropyl methylcellulose acetate succinate (HPMCAS), hydroxypropyl methylcellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), waxes, fatty acids, EUDRAGIT™ L100-5.5, or any other enteric polymer used to coat capsules for ingestion. The coating may be selectively applied onto the capsule 100. In some examples, the capsule 100 may be formed of a gastroresistant material with only contact at interface 106 formed of a gastrosoluble material.

[0030] A coating can be applied over the gastro-soluble material, and when the coating is dissolved or degraded by gastric fluids, the gastro-soluble material degrades and the capsule 100 fragments into at least two portions that can pass through. In some examples, the coating can be applied in a thin layer over the opening 114, and the coating over the opening 114 degrades rapidly upon ingestion, allowing release of the drug. In some examples, a first material can be applied over a portion of the capsule 100 while a second material is applied as a coating over the opening 114, and the second material degrades more readily than the first material in gastric fluids, allowing release of the drug.

[0031] 2 illustrates a capsule 200 component for extended drug release having release openings 214 on one side of the capsule 200, according to at least some embodiments. The capsule 200 may include a first component 202 having a buoyant chamber 208, an interface 206, and an interface edge 210 similar to the first component 102, buoyant chamber 108, an interface 106, and an interface edge 110 of FIG. 1. Similarly, the second portion 204 may be similar to the second portion 104 of FIG. 1, except for the openings 214. The openings 214 are located on only one side of the capsule 200, and by reducing the number of openings 214 compared to the capsule 100, the release rate of the drug may be correspondingly reduced.

[0032] 3 illustrates components of a capsule 300 for extended drug release having snap fasteners 316 for securing the components together, according to at least some embodiments. The capsule 300 includes a first portion 302 and a second portion 304. The first portion 302 includes an interface 316, an interface edge 310, and a buoyant chamber 308 similar to those described above with respect to FIG. 1. The first portion 302 and the second portion 304 each have an elliptical solid shape that combine to form the capsule 300, which may have the same elliptical footprint as the capsule 100, but the first portion 302 and the second portion 304 are split along the length of the capsule, rather than across the middle portion as in FIGS. 1 and 2.

[0033] At the end of the interface 306 is a snap fastener 316. The snap fastener 316 may include a flexible element or filament that deforms when the first and second portions 302, 304 are joined together, holding the first and second portions 302, 304 together within the capsule 300. The snap fastener 316 may also provide a keyed portion to align the first and second portions 302, 304 for a snug, full fit. In some examples, the snap fastener 316 may provide additional surface area onto which an adhesive may be applied to secure the first and second portions 302, 304 together. The adhesive should be a food grade adhesive that provides a securing force to hold the snap fastener 316 together.

[0034] The second portion 304 may include a groove 318 for receiving the snap fastener 316. In some examples, the groove 318 may include a ridge or lip that deforms the snap fastener 316 when pressed together, the deformation causing a retaining hook of the snap fastener 316 to engage the ridge to hold the first portion 302 and the second portion 304 together.

[0035] The second portion 304 includes a single opening 314 opposite the interface 312 that, when assembled, is adjacent the interfacing edge 310. As mentioned above, there may be multiple openings 314 to enhance the release rate of the drug.

[0036] When assembled, the capsule 300 floats with the first portion 302 above the second portion 304 and the opening 314 is submerged, allowing release of the drug through the opening 314 .

[0037] FIG. 4 illustrates components of a capsule 400 for extended drug release having a friction fit to secure the components together, according to at least some embodiments. The capsule 400 includes a first portion 402 and a second portion 404 similar to the first portion 302 and the second portion 304 of FIG. 3 and includes or encloses a buoyant chamber 408 and an opening 414. The components of the capsule 400 are joined together with a friction fit. In particular, the surface 406 and the surface 420 receive the interface 412 and the surface 422. The interface edge 410 can further engage the second portion 404 to provide a surface for contact and adhesion. The second portion 404 nests within the first portion 402 with the surface 420 frictionally engaging and mating with the surface 422 to secure the first portion 402 to the second portion 404. The surface 420 or the surface 422 may be coated with an adhesive or other material to secure the friction fit as described above with respect to FIG. 3. In some examples, the adhesive or other material may be a material that is degradable by gastric fluids, such that the material adhering first portion 402 to second portion 404 degrades in gastric fluids to release capsule 400 into smaller components after the drug is released. For example, after the outer coating of capsule 400 degrades or dissolves in gastric fluids, the material adhering first portion 402 and second portion 404 may rapidly degrade in gastric fluids to release the capsule for passage through the stomach.

[0038] In some examples, the capsule 400 may be formed from one or more materials, such as a composite of materials. In some examples, the first portion 402 and the second portion 404 may each be formed from different materials, and in some examples, the first portion 402 and the second portion 404 may each be formed from multiple materials in different layers. In one particular example, the first portion 402 and the second portion 404 may each be formed from a combination of polylactic acid (PLA) and a composite material including hypromellose acetate succinate (HPMCAS), polyvinyl alcohol (PVA), and PLA. For example, the surface 406 and the interface edge 410 may each be formed from PLA, and the remainder of the first portion 402, such as the walls surrounding and defining the buoyant chamber 408, may be formed from a composite material. Similarly, in certain examples, the second portion may be formed from a combination of materials.

[0039] In some examples, other materials may be selected for various purposes and / or properties, such as swelling characteristics, manufacturability, and other such properties, for one or more portions of capsule 400. For example, the portion of the capsule surrounding opening 414 may be formed of a non-swelling material (e.g., PLA) so that the size of the opening is consistently controlled and does not change as the material begins to swell. Different walls or surfaces of capsule 400 may be formed of composite materials based on selected or desired dissolution rates in gastric fluids, such that capsule 400 disintegrates and releases the active ingredient(s) at approximately the same time or shortly after it is expected.

[0040] 2-4 above are provided for illustrative purposes only. There may be other fastening means and mechanisms other than those described above, as well as other shapes and configurations of capsule 100 having first portion 102 and second portion 104. There may be additional components, alternative planes dividing the portions, and adhesives, coatings, or other means of fastening portions of capsule 100 together.

[0041] 5A-5E show exemplary stages of drug release from a capsule 500 in a patient's stomach 502 over a period of time, according to at least some embodiments. The capsule 500 contains a drug 510 for a particular treatment of the patient that has been previously ingested by the patient. The stomach 502 and capsule 500 are shown for illustrative purposes and are not necessarily drawn to scale. The capsule 500 includes a buoyant chamber 508 and an opening 514 similar to those shown and described above with a coating 504 surrounding the capsule 500. The capsule 500 floats in the gastric fluid 506, with the buoyant chamber 508 above the drug 510 and the opening 514 submerged in the gastric fluid 506.

[0042] 5A shows capsule 500 immediately after ingestion by a patient. Coating 504 is largely undisturbed and intact from ingestion of capsule 500, except for opening 514, which is uncovered, allowing for zero order release kinetics from or near the moment of ingestion. In some examples, opening 514 may be coated with a thin coating similar to coating 504 or more readily dissolving that disintegrates rapidly upon ingestion.

[0043] 5B shows capsule 500 after a period of time, such as 1 to 3 days. Coating 504 is thinner and coating 504 is slowly dissolved or degraded by gastric fluids 506. Drug 510 is reduced as it diffuses through openings 514 into gastric fluids 506 for absorption by the patient.

[0044] Figure 5C shows capsule 500 after an additional period of time has passed from Figure 5B, e.g., one to three days. Coating 504 is now thinner, and coating 504 is slowly dissolved or degraded by gastric fluids 506. Drug 510 is further reduced as it is dispersed through openings 514 into gastric fluids 506 for absorption by the patient.

[0045] 5D shows capsule 500 after further time has passed, for example, one to three days. Coating 504 has disappeared and no longer covers capsule 500. Drug 510 is similarly absent. Gastric fluids 506 are in direct contact with capsule 500, as well as the walls of buoyant chamber 508. Capsule 500 begins to degrade upon contact with gastric fluids 506.

[0046] 5E shows capsule 500 breaking down into components and expelling from stomach 506. Capsule 500 fragments into multiple pieces that are smaller and more easily passed. Additionally, buoyant chamber 508 breaks or fragments, releases gas, is no longer buoyant, and sinks in the gastric fluid. Although capsule 500 is shown in two pieces, in some instances capsule 500 may break into more than two pieces and dissolve completely upon direct contact with gastric fluid.

[0047] Although the capsule 500 is shown floating on the gastric fluid 506, the capsule 500 need not float and may sink below the surface of the gastric fluid 506. In some examples, the capsule 500 may sink to a predetermined depth, such as the middle of the stomach, near the top, or near the bottom of the stomach, based on the buoyancy of the capsule 500. The depth of the capsule 500 may change over time as well, for example, the capsule 500 slowly sinks from the surface to the bottom of the gastric fluid 506 over the course of drug release in response to changes in buoyancy as the drug is released and as the capsule 500 begins to degrade. In some examples, the buoyant chamber may include a foam that degrades over time, which progressively reduces the buoyancy of the capsule 500 over time. Additionally, the composition of the gastric fluid 506 may change over time, for example based on the patient's eating habits, which may cause the capsule 500 to sink or rise to different depths in the stomach.

[0048] 6A-6D show charts of cumulative drug release over time for various capsule designs, according to at least some embodiments. Drug was released from capsules subjected to United States Pharmacopeia (USP) dissolution testing.

[0049] 6A shows a drug release chart for a capsule 100 having openings 114 on both sides of the capsule 100 over a total period of three days. As shown in the figure, the cumulative drug release increases in a manner that can be approximated by a linear trend line until all of the drug is released. The release from the capsule 100 had zero order release kinetics over the three day period.

[0050] 6B shows a drug release chart over a four day period for capsule 200, which has openings 214 on only one side of capsule 200. The only difference between capsule 100 and capsule 200 is the number of openings, which are twice as many for capsule 100. Drug release also had zero order kinetics, but it took four days for the drug to be completely released instead of three days for capsule 100.

[0051] Figures 6C and 6D show drug release charts for capsule 400 in the same dissolution test over a period of 7 days. Capsule 400 in Figure 6C featured additional openings that allowed for drug release at a faster rate than capsule 400 in 6D. As shown in Figures 6C and 6D, capsule 400 was able to maintain zero order drug release kinetics for a period of more than 7 days.

[0052] 7 and 8 show example flow diagrams illustrating processes 700 and 800 according to at least some examples. These processes, and other processes described herein, are illustrated as logical flow diagrams, each operation of which represents a sequence of operations that may be performed by a user, by hardware, by computer instructions, or a combination thereof. Although illustrated as a sequence of logical flow diagrams, some or all of the operations may be completed in a different order or simultaneously. Processes 700 and 800 may also be performed repeatedly or only once.

[0053] FIG. 7 shows a simplified flow chart illustrating a process 700 for determining a capsule design for extended drug release, according to at least some embodiments. The process 700 begins with determining 702 the volume of the gas compartment. A larger air compartment provides greater buoyancy to the capsule, allowing the capsule to float in gastric fluid before, during, or even after a meal. However, a larger air compartment also limits the amount of drug contained in the capsule. The capsule may be limited in size by the limits of safe ingestion by the patient, thereby limiting the volume divided between the buoyant chamber and the drug. In some examples, the volume of the air chamber may be about 40 percent of the total volume of the capsule, balancing the buoyancy against the volume of drug delivered. In some examples, the volume may range from zero to 100 percent. In some examples, the volume may be less than 50 percent, while in some examples, the volume may be greater than 50 percent. The volume may be determined as a percentage of the total volume, or may be expressed as a volume based on a desired buoyancy, such as a gas volume sufficient to make the capsule float in gastric fluid based on the density of the gastric fluid versus the overall or average density of the capsule. Although a gas chamber is described above, the method is intended to encompass determining the volume or buoyancy of non-gaseous buoyancy devices, such as the foams mentioned above.

[0054] Block 704 includes determining capsule size. The larger the capsule, the greater the volume contained therein, but may be more difficult to ingest. In some examples, the capsule may be approximately 16 millimeters by 10 millimeters by 6 millimeters. In some examples, the capsule dimensions may vary from 1 to 2 millimeters to 30 millimeters in any particular dimension. The size of the capsule may be determined based on the patient, for example, an adult patient will receive a larger size capsule than a child patient. The age of the patient or other patient characteristics or other factors may influence the determination of the capsule size.

[0055] At blocks 706 and 708, the process 700 includes determining the number of openings in the capsule as well as the size of the openings. The number of openings and the size of the openings each affect the release rate of the drug. A larger number of release openings results in a faster release rate, and similarly, a larger size of the openings results in a faster release rate. In some examples, the number of openings may range from one to thousands of microscopic holes. In some examples, the openings may have a diameter or effective diameter ranging from one to two millimeters. In some examples, the openings may range in diameter from a fraction of a millimeter to several millimeters. Additionally, blocks 706 and 708 may include determining the shape of the openings, such as a circular opening, a square opening, or other such shape.

[0056] At block 710, the process 700 includes determining and considering the physical properties of the drug, particularly in determining the release rate of the drug. The physical properties of the drug affect the release rate of the drug. Examples of relevant physical properties include viscosity, density, solubility, absorption rate, caking potential, or hygroscopicity. As an example, a drug with high solubility will be released at a faster rate than a drug with low solubility. Similarly, a drug with low viscosity and low density will have a higher release rate than a drug with high viscosity and high density. These physical properties are considered in determining the size and number of the openings described above, as well as the volume of the capsule and the volume of the gas chamber, or are improved by adding excipients mixed with the drug to modify the dispersion, solubility, aggregation, or other properties of the drug. For example, a drug with low viscosity may permeate rapidly through a large opening, such as an opening of about 2 mm, but may be slowed using an opening with a diameter of less than 1 mm.

[0057] At block 712, the process includes determining a compression force for the drug into the capsule. The compression force determines the density of the capsule as well as the amount of drug that can be loaded, which affects the release rate. Additionally, the compression force can slow the release of the drug, for example, if the force is high and caking is more likely.

[0058] The factors that go into the design of a capsule can be interrelated and the factors can be determined simultaneously or an iterative process can be used to finalize the capsule design, for example starting with a patient treatment profile that defines the drug release rate and duration and a black box or sample capsule design, adjusting the above parameters to arrive at the desired release rate, residence time, and capsule size.

[0059] 8 shows a simplified flowchart illustrating a process 800 for creating manufacturing instructions for a capsule for extended drug release, according to at least some embodiments. Process 800 can be performed by a computing device, such as the computing devices described below. Process 800 begins at block 802 by receiving design characteristics. The design characteristics may include any or all of the elements and features described and determined with respect to process 700 above, such as drug density, capsule volume, and other such elements.

[0060] At block 804, the computing device may determine a capsule design based on the design characteristics received at block 802. As described above with respect to process 700, an iterative process may be used to determine the capsule design. In some examples, the capsule may be designed parametrically or based on a set of variables, where the variables are interrelated based on relationships between properties, such as increasing the number of openings increasing the release rate. The capsule design may be determined as a list of parameters, such as volume, gas volume, drug volume, number of openings, and opening size, or in some examples, the computing device may output a three-dimensional model of the capsule design.

[0061] At block 806, the computing device may generate manufacturing instructions for manufacturing the capsule based on the capsule design using a manufacturing device. The manufacturing device may be any suitable manufacturing device, such as a three-dimensional printer or other manufacturing device described below with respect to FIG. 9. The manufacturing instructions may be communicated to the manufacturing device for manufacturing the capsule.

[0062] At block 808, the computing device may create manufacturing instructions for coating an outer layer on the capsule. An outer layer may be selected and its thickness and placement may be determined based on the design characteristics described above. Additionally, selective application of the outer layer may be included in the manufacturing instructions. Additionally, multiple layers of different outer layers may be applied to the capsule based on desired characteristics such as residence time in gastric fluids. The manufacturing instructions may then be communicated to a coating machine to coat the capsule produced at block 808.

[0063] FIG. 9 illustrates an exemplary schematic architecture 900 for implementing techniques related to creating instructions for manufacturing capsules for extended drug release, according to at least some embodiments. The architecture 900 can include a manufacturing control system 902 that communicates with one or more user devices 904(1)-904(N) (hereinafter referred to as "user devices 904") via one or more networks 903 (hereinafter referred to as "networks 903"). The manufacturing control system 902 communicates with the user devices 904 and production equipment 910. The user 901 can use any suitable software, application, etc. operating on the user device 904 or otherwise to provide input to the manufacturing control system 902 to design the capsules as described above. The user device 904 can be operable by one or more users 901 (hereinafter "users 901") to interface with the manufacturing control system 902. The network 903 can include any one or combination of many different types of networks, such as cable networks, the Internet, wireless networks, cellular networks, and other private and / or public networks. User 901 may be any suitable user, including, for example, a customer of an electronic marketplace associated with manufacturing control system 902, or any other suitable user.

[0064] The manufacturing equipment 910 can include any suitable additive and / or subtractive manufacturing equipment configured to perform any suitable manufacturing process. For example, the manufacturing equipment 910 is shown as an extrusion deposition type equipment. Other suitable manufacturing equipment may be configured to perform processes including, for example, a screen printer, a digital inkjet printer, a flexographic printer, an ultraviolet (UV) lithography printer, a laser printer, a pad printer, an electron beam freeform modeling machine, an electron beam melting machine, a selective heat sintering machine, a selective laser sintering machine, a plaster-based solid modeling machine, an additive manufacturing machine, a stereolithography machine, a digital light processing machine, and / or other suitable additive and / or subtractive production machines. In some examples, additional methods and equipment for manufacturing can be used, including vacuum forming, thermoplastic molding, casting, injection molding, molding, and the like.

[0065] The architecture 900 may also include production equipment 910 in communication with at least the manufacturing control system 902 via a secondary network 916. The secondary network 916 may include any one or combination of many different types of networks, as described elsewhere herein.

[0066] Turning now to details of user device 904, user device 904 may be, without limitation, a tablet, a mobile phone, a smart phone, a personal digital assistant (PDA), a laptop computer, a desktop computer, a cloud computing device, or any other suitable device capable of communicating with manufacturing control system 902 via network 903 or any other suitable network. For example, user device 904(1) is illustrated as an example of a smart phone, and user device 904(N) is illustrated as an example of a laptop computer.

[0067] The user device 904 may include a web services application 940 in memory 912. Within the memory 912 of the user device 904, program instructions loadable and executable on the processor 914 may be stored, as well as data created during the execution of these programs. Depending on the configuration and type of the user device 904, the memory 912 may be volatile (such as random access memory (RAM)) and / or non-volatile (such as read only memory (ROM), flash memory, etc.). The web services application 940 stored in the memory 912 may enable the user 901 to interact with the manufacturing control system 902 over the network 903. Such interactions may include, for example, interacting with a user interface provided by the manufacturing control system 902, selecting a capsule design, customizing the capsule design, and ordering the capsule design, performing any other interactions described herein or related to obtaining a capsule, and any other suitable client-server interactions. The manufacturing control system 902, whether associated with an electronic marketplace or not, may host the web services application 940.

[0068] The manufacturing control system 902 may include one or more service provider computers and may host a web services application. These servers may be configured to host a website (or combination of websites) viewable on a user device 904 (e.g., via a web services application 940). A user 901 may access the website to view items (e.g., capsules) that can be ordered from the manufacturing control system 902 (or an electronic marketplace associated with the manufacturing control system 902). These may be presentable to the user 901 via the web services application.

[0069] The manufacturing control system 902 may include at least one memory 918 and one or more processing units (or processors) 920. The processor 920 may be suitably implemented in hardware, computer executable instructions, software, firmware, or a combination thereof. The computer executable instructions, software, or firmware execution of the processor 920 may include computer executable or machine executable instructions written in any suitable programming language to perform the various functions described. The memory 918 may include two or more memories and may be distributed throughout the manufacturing control system 902. The memory 918 may store program instructions that are loadable and executable on the processor 920, as well as data created during the execution of these programs. Depending on the configuration and type of memory that comprises the manufacturing control system 902, the memory 918 may be volatile (such as random access memory (RAM)) and / or non-volatile (such as read only memory (ROM), flash memory, or other memory). The memory 918 may include an operating system 922 and one or more application programs, modules, or services for implementing the techniques described herein, including at least the manufacturing control engine 906. In some examples, the production device 910 is configured to execute the techniques described herein with reference to a manufacturing control system 902 that includes a manufacturing control engine 906.

[0070] The manufacturing control system 902 may also include additional storage 924, which may be removable and / or non-removable storage devices, including but not limited to magnetic storage devices, optical disks, and / or tape storage devices, as well as private or public cloud networks. Disk drives and their associated computer-readable media may provide non-volatile storage of computer-readable instructions, data structures, program modules, and other data for the computing device. Additional storage 924, both removable and non-removable, are examples of computer-readable storage media. For example, computer-readable storage media may include volatile or non-volatile, removable or non-removable media implemented in any suitable manner or technology for storing information, such as computer-readable instructions, data structures, program modules, or other data. As used herein, modules, engines, and components may refer to programming modules executed by computing systems (e.g., processors) that are part of the manufacturing control system 902, user devices 904, and / or production equipment 910.

[0071] The manufacturing control system 902 may also include input / output (I / O) devices and / or ports 926, such as to enable connection to a keyboard, mouse, pen, voice input device, touch input device, display, speakers, printer, or other I / O devices.

[0072] The manufacturing control system 902 may also include a user interface 928. The user interface 928 may be utilized by one of the operators or users 901 to access portions of the manufacturing control system 902. In some examples, the user interface 928 may include a graphical user interface, a programmatic interface such as a web-based application, an application programming interface (API), or other user interface configuration. The manufacturing control system 902 may also include a data store 930. In some examples, the data store 930 may include one or more data stores, databases, data structures, etc. for storing and / or retaining information related to the manufacturing control system 902. Thus, the data store 930 may include databases such as a customer information database 932, a model database 934, and a content item database 936.

[0073] The customer information database 932 may be used to hold information about customers of the manufacturing control system 902, such as users 901. Such information may include, for example, customer account information (e.g., electronic profiles of individual users), customer demographic information, customer payment instrument information (e.g., credit cards, debit cards, bank account information, and other similar payment processing instruments), customer account preferences, customer shipping preferences, customer purchase history, capsule models, customer material preferences, and other similar information about particular customers and sets of customers of the manufacturing control system 902. In some examples, the customer information may be encrypted and decrypted as needed using common encryption techniques. In some examples, the customer information may be de-identified or anonymized, and instead, may only present a general profile that may be selected for manufacturing. In some examples, the information held in the customer information database 932 may be shared with and / or received from an electronic marketplace.

[0074] The model database 934 may be used to store three-dimensional models of capsule designs. The model database 934 may be referenced when the manufacturing control engine 906 is attempting to identify a particular three-dimensional item or to generate manufacturing instructions for a particular capsule. The model database 934 may be configured to store any suitable data capable of storing a representation of a three-dimensional item in any suitable format (e.g., STereoLithography files or STL format).

[0075] The digital content item database 936 can be used to hold information about digital content items for which capsule designs are available. For example, the digital content item database 936 can include a table containing all digital content items available for purchase on an electronic marketplace, information about capsule designs such as release rates and residence times.

[0076] Any suitable computing system or group of computing systems may be used to perform the operations or methods described herein. Figure 10 illustrates an example of a computing device 1000. In one embodiment, a computing device such as a user device 904 or a manufacturing control system 902 combines one or more operations and data stores, which are shown herein as separate subsystems.

[0077] 10 shows a block diagram of an example of a computing device 1000. Computing device 1000 may be any of the computers described herein, including, for example, user device 904 or manufacturing control system 902. Computing device 1000 may be or include, for example, an integrated computer, a laptop computer, a desktop computer, a tablet, a server, or other electronic device.

[0078] Computing device 1000 may include a processor 1040 that interfaces with other hardware via a bus 1005. Memory 1010, which may include any suitable tangible (and non-transitory) computer-readable medium, such as RAM, ROM, EEPROM, etc., may embody program components (e.g., program code 1015) that configure the operation of computing device 1000. Memory 1010 may store program code 1015, program data 617, or both. In some examples, computing device 1000 may include input / output ("I / O") interface components 1025 (e.g., for interfacing with a display 1045, keyboard, mouse, etc.) and additional storage 1030.

[0079] Computing device 1000 executes program code 1015 that configures processor 1040 to perform one or more of the operations described herein. The program code 1015 may reside in memory 1010 or any suitable computer readable medium and may be executed by processor 1040 or any other suitable processor.

[0080] Computing device 1000, by executing program code 1015, can create or receive program data 1017. For example, capsule designs, drug characteristics, capsule characteristics, and patient treatment profiles are all examples of program data 1017 that may be used by computing device 1000 during execution of program code 1015.

[0081] The computing device 1000 may include a network component 1020. The network component 1020 may represent one or more of any components that facilitate a network connection. In some examples, the network component 1020 may facilitate a wireless connection and may include a radio interface such as IEEE 802.11, Bluetooth, or a radio interface for accessing a cellular telephone network (e.g., a transceiver / antenna for accessing a CDMA, GSM, UMTS, or other mobile communication network). In other examples, the network component 1020 may be wired and may include an interface such as Ethernet, USB, or IEEE 1394.

[0082] 10 shows one computing device 1000 with a single processor 1040, a system may include any number of computing devices 1000 and any number of processors 1040. For example, multiple computing devices 1000 or multiple processors 1040 may be distributed across a wired or wireless network (e.g., a wide area network, a local area network, or the Internet). Multiple computing devices 1000 or multiple processors 1040 may perform any of the steps of the present disclosure individually or in coordination with one another.

[0083] Although the present subject matter has been described in detail with respect to certain embodiments thereof, it will be understood that those skilled in the art, upon reaching the foregoing understanding, can easily make modifications, variations, and equivalents to such embodiments. Numerous specific details are described herein to provide a thorough understanding of the claimed subject matter. However, those skilled in the art will understand that the claimed subject matter may be practiced without these specific details. In other instances, methods, apparatus, or systems that would be known to those skilled in the art have not been described in detail so as not to obscure the claimed subject matter. Thus, the present disclosure has been presented by way of example and not by way of limitation, and is not intended to exclude the inclusion of such modifications, variations, and / or additions to the subject matter as would be readily apparent to those skilled in the art.

[0084] Unless otherwise indicated, throughout this specification, descriptions using terms such as "processing," "computing," "calculating," "determining," and "identifying" should be understood to refer to the actions or processes of a computing device, such as one or more computers or similar electronic computing devices or devices, that manipulate or transform data represented as physical electronic or magnetic quantities in the memory, registers, or other information storage, transmission, or display devices of a computing platform. The use of "adapting" or "configuring" herein means open and inclusive language that does not exclude devices adapted or configured to perform additional tasks or steps. Furthermore, the use of "based on" means open and inclusive in that a process, step, calculation, or other action that is "based on" one or more recited conditions or values ​​may in fact be based on additional conditions or values ​​beyond those recited. The headings, lists, and numbering contained herein are for ease of description only and are not intended to be limiting.

[0085] Aspects of the methods disclosed herein may be implemented in the operation of such a computing device. The systems or systems described herein are not limited to a particular hardware architecture or configuration. A computing device may include any suitable configuration of components that provide results conditioned on one or more inputs. Suitable computing devices include general-purpose microprocessor-based computer systems that access stored software that programs or configures computing systems ranging from general-purpose computing devices to special-purpose computing devices that implement one or more aspects of the present subject matter. Any suitable programming, scripting, or other type of language or combination of languages ​​may be used to implement the teachings contained herein in software. Used to program or configure a computing device. The order of the blocks shown in the above examples may be changed. For example, blocks may be rearranged, combined, or divided into sub-blocks. Certain blocks or processes may be executed in parallel.

Claims

1. A long-term release delivery system for a releasable drug comprising: (i) a capsule comprising a first portion and a second portion; and (ii) an outer layer, wherein the first portion includes (i) a sealed buoyant chamber made of a material that causes the capsule to float in gastric fluids, and (ii) a first attachment mechanism made of the same material; the second portion includes a chamber and a second coupling mechanism; the chamber in the second portion defines (i) an interior for holding at least one releasable agent, and (ii) at least one opening in the interior through which the at least one releasable agent is releasable; the second coupling mechanism is configured to cooperate with the first coupling mechanism to secure the first portion to the second portion and completely enclose the chamber in the second portion; the outer layer includes a coating disposed on at least one of the first portion and the second portion; The first connecting mechanism includes: (i) an upper surface of the first linkage connected to an upper surface of the buoyant chamber; (ii) a bottom surface of the first linkage opposite the top surface of the first linkage connected to a bottom surface of the buoyant chamber; (iii) a first side connected to a side of the buoyant chamber, between the top surface of the first linkage mechanism and the bottom surface of the first linkage mechanism; (iv) a second side connected to a side of the buoyant chamber, between the top surface of the first linkage and the bottom surface of the first linkage, opposite the first side; and (v) a wall between the top surface of the first coupling mechanism, the bottom surface of the first coupling mechanism, the first side surface, and the second side surface. having the first coupling mechanism is inserted into the second portion such that the wall is in the second portion; the first coupling mechanism separates the buoyant chamber from the second portion; Extended release delivery system.

2. 10. The long-term release delivery system of claim 1, wherein the buoyant chamber comprises a hollow chamber filled with a gas.

3. 10. The extended release delivery system of claim 1, wherein the capsule includes a third compartment having at least a second releasable agent therein.

4. 10. The long-term release delivery system of claim 1, wherein the capsule further comprises at least a second opening through which the at least one releasable agent is released.

5. 10. The extended release delivery system of claim 1, wherein the capsule is formed from a gastric juice soluble material.

6. A sustained release delivery capsule for a releasable drug comprising a first portion and a second portion, wherein the first portion comprises (i) a sealed buoyant chamber made of a material that suspends the capsule in gastric fluids, and (ii) a first interface made of the same material; the first portion is formed from a first gastric fluid soluble material; the second portion is formed from a second gastric fluid soluble material; The second portion includes a chamber and a second interface; the chamber in the second portion defines (i) an interior for holding at least one releasable agent, and (ii) at least one opening in the interior through which the at least one releasable agent is releasable; the second interface is configured to engage the first interface to secure the first portion to the second portion and completely enclose the chamber in the second portion; The first interface includes: (i) an upper surface of the first interface connected to an upper surface of the buoyant chamber; (ii) a bottom surface of the first interface opposite the top surface of the first interface, connected to a bottom surface of the buoyant chamber; (iii) a first side between the top surface of the first interface and the bottom surface of the first interface, the first side being connected to a side of the buoyant chamber; (iv) a second side connected to a side of the buoyant chamber, between the top surface of the first interface and the bottom surface of the first interface and opposite the first side; and (v) a wall between the top surface of the first interface, the bottom surface of the first interface, the first side surface, and the second side surface. having the first interface is inserted within the second portion such that the wall is within the second portion; the first interface separates the buoyant chamber from the second portion; Extended release delivery capsule.

7. 7. The extended release delivery capsule of claim 6, further comprising an enteric coating on the exterior of the first and second portions.

8. 7. The extended release delivery capsule of claim 6, wherein the first gastric juice soluble material or the second gastric juice soluble material comprises an enteric complex that is soluble in gastric juice for at least three days.

9. 8. The extended release delivery capsule of claim 7, wherein the enteric coating comprises a third portion sealing at least one opening of the capsule and a fourth portion covering at least one portion of the capsule, and the dissolution rate of the third portion is greater than the dissolution rate of the fourth portion.

10. 8. The extended release delivery capsule of claim 7, wherein the enteric coating comprises a third portion sealing at least one opening of the capsule and a fourth portion covering at least one portion of the capsule, and the thickness of the fourth portion is greater than the thickness of the third portion of the enteric coating.

11. 7. The extended release delivery capsule of claim 6, wherein the at least one releasable agent is releasable through the at least one opening for at least three consecutive days before the capsule disintegrates in gastric fluids.

12. 7. The extended release delivery capsule of claim 6, wherein the buoyant chamber encapsulates a biocompatible foam that dissolves in gastric fluids.

13. A releasable drug delivery capsule comprising a first portion, a second portion, and an outer layer, wherein the first portion includes (i) an enclosed buoyant element made of a material that suspends the capsule in a liquid, and (ii) a first interface made of the same material; the first portion includes a liquid soluble material; the second portion includes the liquid soluble material; The second portion includes a chamber and a second interface; the chamber in the second portion defines (i) an interior for holding at least one releasable agent, and (ii) at least one opening in the interior through which the at least one releasable agent is releasable into the liquid; the second interface is configured to engage the first interface to secure the first portion to the second portion and completely enclose the chamber in the second portion; the outer layer includes a coating disposed on at least one of the first portion and the second portion; The first interface includes: (i) an upper surface of the first interface connected to an upper surface of the buoyant chamber; (ii) a bottom surface of the first interface opposite the top surface of the first interface, connected to a bottom surface of the buoyant chamber; (iii) a first side between the top surface of the first interface and the bottom surface of the first interface, the first side being connected to a side of the buoyant chamber; (iv) a second side connected to a side of the buoyant chamber, between the top surface of the first interface and the bottom surface of the first interface and opposite the first side; and (v) a wall between the top surface of the first interface, the bottom surface of the first interface, the first side surface, and the second side surface. having the first interface is inserted within the second portion such that the wall is within the second portion; the first interface separates the buoyant chamber from the second portion; Releasable drug delivery capsules.

14. 14. The releasable drug delivery capsule of claim 13, comprising an outer layer covering the outer surfaces of the first and second portions, coating the first and second interfaces, and the first and second portions being separable in response to the outer layer dissolving in a liquid.

15. 14. The releasable drug delivery capsule of claim 13, wherein the first interface and the second interface are joined by a friction fit.

16. 14. The releasable drug delivery capsule of claim 13, wherein the first interface and the second interface are secured together with an adhesive or a fixing compound.

17. 14. The releasable drug delivery capsule of claim 13, wherein the at least one opening is on a first side of the capsule opposite the buoyant element.

18. 14. The releasable drug delivery capsule of claim 13, wherein the liquid soluble material comprises a complex of a liquid soluble material and an insoluble material.

Images