Drug formulations for maintaining stomach health

Abstract

The present invention provides a formulation that remains in the stomach for at least approximately 24 hours. [Solution] A formulation comprising a first component and a swelling component, wherein the first component and the swelling component are connected, at least one of the first component and the swelling component contains a drug, the swelling component contains an outer lid and a swelling agent, the outer lid is connected to the swelling agent, the swelling component or a part thereof swells when exposed to gastrointestinal fluid, and the outer lid is configured such that the swelling of the swelling agent moves the outer lid outward from the formulation, thereby increasing the dimensions of the formulation, thereby allowing the formulation to be retained in the stomach for at least about 24 hours.

Description

Technical Field

[0001] In some aspects, the present disclosure is directed to a pharmaceutical dosage form having a swellable component, wherein the swellable component is configured to swell in the stomach and increase the size of the pharmaceutical dosage form such that the pharmaceutical dosage form is retained in the stomach for an extended period of time. In other aspects, the present disclosure is directed to methods of design, methods of making, such as using three-dimensional (3D) printing, and methods of delivering a drug to an individual, where such methods are associated with the gastric-retentive pharmaceutical dosage forms described herein.

Background Art

[0002] When administered to an individual, conventional oral pharmaceutical dosage forms are exposed to the natural flow of fluids, semi-solids, and solids through the individual's gastrointestinal system. This natural flow may vary between administrations of the pharmaceutical dosage form to a given individual and across a population of individuals, based on circumstances that vary in relation to the timing of administration of the pharmaceutical dosage form, the timing and size of any meals and / or drinks, the content of meals and / or drinks, and the current gastric phase and residual duration. These circumstances create variability in, for example, the anatomical location of drug delivery, bioavailability, safety profile, and efficacy of pharmaceutical dosage forms that have a certain retention period in the stomach, such as oral pharmaceutical dosage forms.

[0003] All references cited herein, including patent applications and publications, are incorporated herein by reference in their entireties.

Summary of the Invention

[0004] In some aspects, provided herein is a pharmaceutical dosage form comprising a first component and a swellable component, wherein the first component and the swellable component are connected, at least one of the first component and the swellable component comprises a drug, the swellable component or a portion thereof swells upon exposure to gastrointestinal fluid, and swelling of the swellable component or a portion thereof increases the dimensions of the pharmaceutical dosage form, thereby allowing the drug to be retained in the stomach for at least about 24 hours.

[0005] In some embodiments, the swelling component comprises an outer lid and a swelling agent, the outer lid being connected to the swelling agent, and the outer lid being configured to form at least a portion of the outer surface of the drug dosage form. In some embodiments, the surface of the outer lid and a portion of the first component form the outer surface of the drug dosage form. In some embodiments, a portion of the outer lid is operably connected to the dosage form such that swelling of the swelling component causes the outer lid to move outward from the drug dosage form on a hinge. In some embodiments, the outer lid is configured such that swelling of the swelling component causes the entire outer lid to move outward from the drug dosage form. In some embodiments, the drug dosage form further comprises one or more swelling components, each including an outer lid.

[0006] In some embodiments, the swelling component and the first component are configured as two separate layers.

[0007] In some embodiments, the drug dosage form further comprises a second component, and the first and second components are connected, at least partially, via a swellable component. In some embodiments, swelling of the swellable component shifts the relative positions of the first and second components, thereby increasing the dimensions of the drug dosage form. In some embodiments, the first component has a first axis from a first proximal end to a first distal end, the second component has a second axis from a second proximal end to a second distal end, the swellable component has a central axis, and when the swellable component swells, the first and second axes are shifted relative to each other. In some embodiments, the first and second axes are aligned relative to each other when the swellable component does not swell, and rotate relative to each other when the swellable component swells. In some embodiments, the first and second axes become perpendicular to each other when the swellable component swells. In some embodiments, at least a portion of the first component is configured to cooperate with a second component to create a point of rotation.

[0008] In some embodiments, the first and second axes are aligned with each other and, as the swelling component swells, they are shifted away from the central axis. In some embodiments, the drug dosage form further includes a first guide track and a second guide track, and as the swelling component swells, the first component shifts away from the central axis together with the first guide track, and the second component shifts away from the central axis together with the second guide track. In some embodiments, the drug dosage form further includes a third component, a third guide track, a fourth component, and a fourth guide track, and as the swelling component swells, the third component shifts away from the central axis together with the third guide track, and the fourth component shifts away from the central axis together with the fourth guide track.

[0009] In some embodiments, the first component comprises a first drug. In some embodiments, the second component comprises a second drug. In some embodiments, the third component comprises a third drug. In some embodiments, the fourth component comprises a fourth drug.

[0010] In some embodiments, the swelling component includes a core drug. In some embodiments, the swelling component does not include a drug.

[0011] In some embodiments, at least two of the first drug, second drug, third drug, fourth drug, and core drug are the same. In some embodiments, at least two of the first drug, second drug, third drug, fourth drug, and core drug are different from each other.

[0012] In some embodiments, at least one of the first drug, second drug, third drug, fourth drug, and core drug is poorly water-soluble.

[0013] In some embodiments, one of the first drug, second drug, third drug, fourth drug, and core drug is located within a compartment embedded in the substrate material.

[0014] In some embodiments, the first component, second component, third component, and / or fourth component include a drug contained within the compartment. In some embodiments, the compartment includes a plug.

[0015] In some embodiments, the first component, second component, third component, and / or fourth component include two or more drug-filled compartments.

[0016] In some embodiments, the drug dosage form is an oral drug dosage form.

[0017] In other embodiments, a commercially available batch of any drug dosage form described herein is provided, the commercially available batch having a standard deviation of about 0.05 or less for each of the following: the amount of drug in the drug dosage form, the weight of the drug dosage form, the maximum cross-sectional dimension of the oral drug dosage form, the cross-sectional dimension perpendicular to the maximum cross-sectional dimension of the oral drug dosage form, the maximum cross-sectional dimension of the oral drug dosage form after swelling of the swelling component, and the cross-sectional dimension perpendicular to the maximum cross-sectional dimension of the oral drug dosage form after swelling of the swelling component. In some embodiments, the commercially available batch contains at least about 1000 drug dosage forms. In some embodiments, the drug dosage forms are manufactured by 3D printing techniques.

[0018] In other embodiments, provided herein are methods for three-dimensional (3D) printing of any drug dosage form described herein, the methods comprising (a) extruding a first component or a portion thereof, and (b) extruding a swelling component or a portion thereof. In some embodiments, the extruding is via melt extrusion deposition (MED). In some embodiments, the extruding of the first component or a portion thereof and the extruding of the swelling component or a portion thereof are performed by different print heads.

[0019] In other embodiments, provided herein are methods for preparing drug dosage forms by three-dimensional (3D) printing, wherein the drug dosage form comprises a first component, a second component, and a swelling component, and the method comprises (a) extruding the material of the first component, (b) extruding the material of the second component, and (c) extruding the material of the swelling component. In some embodiments, the extruding is via melt extrusion deposition (MED). In some embodiments, the extruding of each material is performed by different print heads.

[0020] In some embodiments, the drug dosage forms are 3D printed using a layer-by-layer technique.

[0021] In other embodiments, the foregoing provides a method for delivering a drug into an organism and enabling the drug to be retained in the organism's stomach for an extended period of time, the method comprising orally administering any drug dosage form described herein to the organism.

[0022] It will be understood by those skilled in the art that modifications to the forms and details of the implementations described herein can be made without departing from the scope of this disclosure. In addition, although various advantages, embodiments, and purposes have been described with reference to various implementations, the scope of this disclosure should not be limited by reference to such advantages, embodiments, and purposes. [Brief explanation of the drawing]

[0023] [Figure 1A] The diagram shows an exemplary drug dosage form containing a swelling component, including an outer lid (e.g., Figure 1A, 104). [Figure 1B] The diagram shows an exemplary drug dosage form containing a swelling component, including an outer lid (e.g., Figure 1A, 104). [Figure 1C] The diagram shows an exemplary drug dosage form containing a swelling component, including an outer lid (e.g., Figure 1A, 104). [Figure 1D] The diagram shows an exemplary drug dosage form containing a swelling component, including an outer lid (e.g., Figure 1A, 104). [Figure 1E]1 shows a diagram of an exemplary pharmaceutical dosage form comprising a swellable component including an outer lid (e.g., 104 in FIG. 1A). [Figure 1F] 1 shows a diagram of an exemplary pharmaceutical dosage form comprising a swellable component including an outer lid (e.g., 104 in FIG. 1A). [Figure 1G] 1 shows a diagram of an exemplary pharmaceutical dosage form comprising a swellable component including an outer lid (e.g., 104 in FIG. 1A). [Figure 1H] 1 shows a diagram of an exemplary pharmaceutical dosage form comprising a swellable component including an outer lid (e.g., 104 in FIG. 1A). [Figure 1I] 1 shows a diagram of an exemplary pharmaceutical dosage form comprising a swellable component including an outer lid (e.g., 104 in FIG. 1A). [Figure 1J] 1 shows a diagram of an exemplary pharmaceutical dosage form comprising a swellable component including an outer lid (e.g., 104 in FIG. 1A). [Figure 2A] 2 shows a diagram of an exemplary pharmaceutical dosage form comprising a first component in the form of a layer (e.g., layer 202 in FIG. 2A) and a swellable component in the form of a layer (e.g., layer 204 in FIG. 2A). [Figure 2B] 2 shows a diagram of an exemplary pharmaceutical dosage form comprising a first component in the form of a layer (e.g., layer 202 in FIG. 2A) and a swellable component in the form of a layer (e.g., layer 204 in FIG. 2A). [Figure 2C] 2 shows a diagram of an exemplary pharmaceutical dosage form comprising a first component in the form of a layer (e.g., layer 202 in FIG. 2A) and a swellable component in the form of a layer (e.g., layer 204 in FIG. 2A). [Figure 3A] Depicted is a diagram of an exemplary pharmaceutical dosage form comprising a first component (e.g., 302 in FIG. 3A) having a first axis (e.g., 308 in FIG. 3A) and a second component (e.g., 304 in FIG. 3B) having a second axis (e.g., 310 in FIG. 3A), wherein when the swellable component (e.g., 306 in FIG. 3A) swells, the first axis and the second axis rotate relative to each other (FIG. 3B). [Figure 3B] Depicted is a diagram of an exemplary pharmaceutical dosage form comprising a first component (e.g., 302 in FIG. 3A) having a first axis (e.g., 308 in FIG. 3A) and a second component (e.g., 304 in FIG. 3B) having a second axis (e.g., 310 in FIG. 3A), wherein when the swellable component (e.g., 306 in FIG. 3A) swells, the first axis and the second axis rotate relative to each other (FIG. 3B). [Figure 3C] A diagram of an exemplary drug dosage form is shown, comprising a first component (e.g., Figure 3A, 302) having a first axis (e.g., Figure 3A, 308) and a second component (e.g., Figure 3B, 304) having a second axis (e.g., Figure 3A, 310), wherein when a swelling component (e.g., Figure 3A, 306) swells, the first and second axes rotate relative to each other (Figure 3B). [Figure 4A] The diagrams show exemplary drug dosage forms both before (Figures 4A and 4C) and after (Figures 4B and 4D) swelling of the swelling component, illustrating that when the swelling component swells, a point on the first axis of the first component (e.g., Figure 4A, 412) is shifted away from the central axis of the swelling component (e.g., Figure 4A, 402). [Figure 4B] The diagrams show exemplary drug dosage forms both before (Figures 4A and 4C) and after (Figures 4B and 4D) swelling of the swelling component, illustrating that when the swelling component swells, a point on the first axis of the first component (e.g., Figure 4A, 412) is shifted away from the central axis of the swelling component (e.g., Figure 4A, 402). [Figure 4C] The diagrams show exemplary drug dosage forms both before (Figures 4A and 4C) and after (Figures 4B and 4D) swelling of the swelling component, illustrating that when the swelling component swells, a point on the first axis of the first component (e.g., Figure 4A, 412) is shifted away from the central axis of the swelling component (e.g., Figure 4A, 402). [Figure 4D] The diagrams show exemplary drug dosage forms both before (Figures 4A and 4C) and after (Figures 4B and 4D) swelling of the swelling component, illustrating that when the swelling component swells, a point on the first axis of the first component (e.g., Figure 4A, 412) is shifted away from the central axis of the swelling component (e.g., Figure 4A, 402). [Modes for carrying out the invention]

[0024] In this specification, in several embodiments, drug dosage forms comprising a swelling component, or at least a portion thereof, swells upon exposure to gastrointestinal fluid, and the swelling of the swelling component increases the dimensions of the drug dosage form, thereby enabling the drug to be retained in the stomach for an extended period (e.g., at least about 24 hours). The drug dosage forms described herein are at least in part based on the inventors' unique insights and discoveries regarding the design, construction, and manufacture of drug dosage forms comprising a swelling component that undergoes a precisely designed size change upon swelling of the swelling component so that the drug dosage form is retained in the stomach. The drug dosage forms of this application can be designed to have controlled swelling (e.g., size, direction, shape, and rate) of the swelling component such that the expanded form of the drug dosage form is a specific, mechanically sound form that allows for extended gastric retention without interfering with normal gastric function. The drug dosage forms of this application can also be configured to release the drug therefrom according to any desired drug release profile (e.g., sustained-release profile, delayed-sustained-release profile, pulsed-release profile). The inventors have demonstrated that such drug dosage forms can be easily manufactured using three-dimensional (3D) printing techniques.

[0025] Accordingly, in some embodiments, a drug dosage form is provided comprising a first component and a swelling component, wherein the first component and the swelling component are connected, and at least one of the first component and the swelling component contains a drug, and the swelling component or a portion thereof swells when exposed to gastrointestinal fluid, and the swelling of the swelling component or a portion thereof increases the dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for an extended period, for example, at least about 24 hours. In some embodiments, the first component surrounds the swelling component, including partially surrounding it, for example, forming a shell around at least a portion of the swelling component.

[0026] In another embodiment, a drug dosage form is provided comprising a first component and a swelling component, wherein the first component and the swelling component are connected, the swelling component comprises an outer lid and a swelling agent, the outer lid is connected to the swelling agent, the outer lid is configured to form at least a portion of the outer surface of the drug dosage form, at least one of the first component and the swelling component comprises a drug, the swelling component or a portion thereof swells when exposed to gastrointestinal fluid, the swelling of the swelling component or a portion thereof increases the dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for at least about 8 hours, for example, at least about 12 hours, 18 hours, or 24 hours.

[0027] In other embodiments, a drug dosage form is provided comprising a first component and a swelling component, wherein the first component is a first layer and the swelling component is a second layer, the first component and the swelling component are connected, and at least one of the first component and the swelling component contains a drug, the swelling component swells when exposed to gastrointestinal fluid, the swelling of the swelling component increases the dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for at least about 8 hours, for example, at least about 12 hours, 18 hours, or 24 hours. In some embodiments, the swelling component comprises an outer lid.

[0028] In other embodiments, a drug dosage form is provided comprising a first component, a second component, and a swelling component, the first and second components being connected at least partially via the swelling component, and at least one of the first component, the second component, and the swelling component containing a drug, the first component having a first axis from a first proximal end to a first distal end, the second component having a second axis from a second proximal end to a second distal end, and the swelling component having a central axis, the first and second axes being aligned so as to be parallel or substantially parallel to each other when the swelling component is not swollen (e.g., under administration), and rotating relative to each other when the swelling component swells, the swelling component swells when exposed to gastrointestinal fluid, and the swelling of the swelling component or part thereof increases the dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for at least about 8 hours, for example, at least about 12 hours, 18 hours, or 24 hours.

[0029] In other embodiments, a drug dosage form is provided comprising a first component, a second component, and a swelling component, the first and second components being connected at least partially via the swelling component, and at least one of the first component, the second component, and the swelling component containing a drug, the first component having a first axis from a first proximal end to a first distal end, the second component having a second axis from a second proximal end to a second distal end, the swelling component having a central axis, the first and second axes being aligned with each other (for example, when the first and second axes are located from top to bottom through the drug dosage form), the swelling component being shifted away from the central axis when it swells, the swelling component swelling when exposed to gastrointestinal fluid, and the swelling of the swelling component or part thereof increasing the dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for at least about 8 hours, for example, at least about 12 hours, 18 hours, or 24 hours. In some embodiments, the first axis, the second axis, and the central axis are parallel or substantially parallel. For the purpose of describing the drug dosage form, in some embodiments, the first axis and the second axis (when guided by the directional movement of the expanding dosage form) may each include a point, and the points on the first axis and the points on the second axis are shifted away from the central axis as the swelling component swells. In some embodiments, the first axis is further included in the drug dosage form, and in some embodiments, the drug dosage form further includes a first guide track and a second guide track, and as the swelling component swells, the first component shifts away from the central axis together with the first guide track, and the second component shifts away from the central axis together with the second guide track. In some embodiments, the drug dosage form further comprises a third component, a third guide track, a fourth component, and a fourth guide track, wherein when the swelling component swells, the third component shifts away from the central axis together with the third guide track, and the fourth component shifts away from the central axis together with the fourth guide track.

[0030] In other embodiments, a commercially available batch of the drug dosage forms described herein is provided. In some embodiments, the commercially available batch contains at least about 1000 drug dosage forms. In some embodiments, the commercially available batch has a standard deviation of about 0.05 or less for each of the following: the amount of drug in the drug dosage form, the weight of the drug dosage form, the maximum cross-sectional dimension of the oral drug dosage form, the cross-sectional dimension perpendicular to the maximum cross-sectional dimension of the oral drug dosage form, the maximum cross-sectional dimension of the oral drug dosage form after swelling of the swelling component, and the cross-sectional dimension perpendicular to the maximum cross-sectional dimension of the oral drug dosage form after swelling of the swelling component.

[0031] In other embodiments, a method for three-dimensional (3D) printing of the drug dosage form described herein is provided. In some embodiments, the drug dosage form comprises a first component and a swelling component, and the method comprises (a) dispensing the first component or a portion thereof, and (b) dispensing the swelling component or a portion thereof. In some embodiments, the drug dosage form comprises a first component, a second component, and a swelling component, and the method comprises (a) dispensing the material of the first component, (b) dispensing the material of the second component, and (c) dispensing the material of the swelling component.

[0032] I. Definition For the purposes of interpreting this Spec., the following definitions apply, and wherever appropriate, a term used in the singular also includes the plural, and vice versa. In the event of any conflict between the following definitions and any document incorporated herein by reference, the following definitions shall prevail.

[0033] As used herein, the term “individual” refers to mammals, including but not limited to humans, cattle, horses, felines, canines, rodents, rats, mice, dogs, or primates. In some embodiments, the individual is a human individual.

[0034] As used herein, the terms “comprising,” “having,” “containg,” and “including,” as well as other similar forms and their grammatical equivalents, are intended to be semantically equivalent and are intended to be open-ended in that the items or items following any one of these words are not intended to be an exhaustive list of such items or items, or to be limited to only the listed items or items. For example, an article “comprising” components A, B, and C may consist of (i.e., consist only of) components A, B, and C, or may contain one or more other components in addition to components A, B, and C. Accordingly, “comprises” and its similar forms, and their grammatical equivalents, are intended and understood to include disclosures of embodiments that “essentially consist of” or “consist of.”

[0035] Where a range of values ​​is provided, unless the context clearly indicates otherwise, it is understood that each intervening value up to one-tenth of the lower limit between the upper and lower limits of that range and any other stated or intervening value within that stated range is included in this disclosure, subject to any specifically excluded limits within the stated range. If the stated range includes one or both of the limits, the range excluding one or both of the included limits is also included in the disclosure.

[0036] In this specification, any reference to “about” a value or parameter includes (and describes) variations relating to the value or parameter itself. For example, a statement referring to “about X” includes a statement of “X.”

[0037] As used herein, including in the attached claims, the singular forms "a," "or," and "the" refer to multiple subjects unless the context clearly indicates otherwise.

[0038] II. Drug Dosage Forms for Gastric Preservation The drug dosage forms provided herein include a swellable component configured to swell upon exposure to gastrointestinal fluid, the swelling of the swellable component or a portion thereof resulting in an increase in the dimensions of the drug dosage form so that it can be retained in the stomach for an extended period. In some embodiments, the drug dosage form is configured with consideration for desired functions or attributes required during the drug dosage form's administration lifecycle and the characteristics of the individual to whom the drug dosage form is administered. For example, in some embodiments, the drug dosage form has an administration state, the administration state of the drug dosage form is configured for oral administration to an individual, for example, the drug dosage form is configured so that the drug dosage form can be swallowed and moved into the stomach. In some embodiments, the drug dosage form has a gastric retention state, the gastric retention state of the drug dosage form is configured such that the dimensions of the drug dosage form prevent the passage of the drug dose through the pylorus or a portion thereof, thereby resulting in gastric retention. In some embodiments, the drug dosage form has an extrusion state, the extrusion state of the drug dosage form or a component thereof is configured such that it can pass through the pylorus and the drug dosage form is removed from the stomach. As detailed herein, numerous mechanisms are described in which swelling of a swelling component or a part thereof increases the size of the drug dosage form (e.g., transition from administration state to gastric retention state) so that the drug dosage form is retained in the stomach for an extended period.

[0039] A. Exemplary mechanisms of drug dosage forms In some embodiments, the drug dosage form comprises a first component and a swelling component, the first component and the swelling component are connected, the swelling component comprises an outer lid and a swelling agent, the outer lid is connected to the swelling agent, the outer lid is configured to form at least a portion of the outer surface of the drug dosage form, at least one of the first component and the swelling component comprises a drug, and the swelling component, such as a swelling agent, or a portion thereof, swells when exposed to gastrointestinal fluid, and the swelling of the swelling component or a portion thereof increases the dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for an extended period. In some embodiments, the surface of the outer lid and a portion of the first component form the outer surface of the drug dosage form. In some embodiments, a portion of the outer lid is operably connected to the drug dosage form such that the swelling of the swelling component causes the outer lid to move outward from the drug dosage form on a hinge. In some embodiments, the outer lid is configured such that the swelling of the swelling component causes the entire outer lid to move outward from the drug dosage form. A drug may contain one or more of the characteristics described in the drug dosage form.

[0040] In some embodiments, the drug dosage form comprises two or more swelling components, such as 2, 3, 4, or 5. In some embodiments, each swelling component comprises an outer lid and a swelling agent.

[0041] For illustrative purposes, as shown in Figure 1A, drug dosage form 100 comprises a first component 102 and a swelling component, the swelling component comprising a swelling agent and an outer lid 104. In Figure 1A, before the swelling component expands, the swelling agent is in the internal space of the drug dosage form, and the outer lid of the swelling component forms the outer surface of the drug dosage form. In some embodiments, the drug dosage form is configured to allow gastrointestinal fluid to penetrate the drug dosage form and come into contact with the swelling agent. In some embodiments, the drug dosage form includes features such as pores around and / or inside the outer lid to allow gastrointestinal fluid to penetrate the drug dosage form and come into contact with the swelling agent. In Figure 1B, after the swelling agent 106 of the swelling component expands, the dimensions of the drug dosage form 100 increase relative to the pre-expansion state (e.g., administration state). In some embodiments, a portion of the outer lid of the swelling component remains operably connected to the drug dosage form (e.g., a hinge mechanism shown in Figure 1B). In some embodiments, the outer lid is completely separated from the original surface of the drug dosage form (e.g., a sliding drawer mechanism, not shown). In some embodiments, the outer lid provides structural and / or mechanical stability to the drug dosage form or its components, such as a swelling agent. In some embodiments, the outer lid is connected to the swelling agent so that the outer lid and the swelling agent remain connected during the swelling of the swelling agent. In some embodiments, the drug dosage form 100 comprises a first component 102. In any embodiment described herein, the first component and / or swelling component comprises a drug.

[0042] Additional exemplary drug dosage forms containing a swelling component including a swelling agent and an outer lid are provided in Figures 1C–1J. As shown in Figures 1C and 1D, the drug dosage form is in the form of a capsule and contains a single swelling component including a U-shaped outer lid and a swelling agent, the U-shaped outer lid forming the outer surface of the drug dosage form. As shown in Figures 1E and 1F, the drug dosage form is in the form of a capsule and contains two swelling components, each swelling component containing a U-shaped outer lid and a swelling agent, the U-shaped outer lid forming the outer surface of the drug dosage form. As shown in Figures 1G and 1H, the drug dosage form is in the form of a capsule and contains a single swelling component including two U-shaped outer lids and a swelling agent, each U-shaped outer lid forming the outer surface on the opposing sides of the drug dosage form. In Figures 1C–1H, when the swelling agent of the swelling component swells, the U-shaped outer lid protrudes from the drug dosage form using a hinge mechanism. As shown in Figures 1I and 1J, the drug dosage form is in the form of a capsule and contains a swellable component that, when swollen, protrudes from the drug dosage form using a sliding drawer mechanism.

[0043] In some embodiments, the drug dosage form comprises a first component and a swelling component, the first component being a first layer and the swelling component being a second layer, the first component and the swelling component being connected, at least one of the first component and the swelling component containing the drug, the swelling component swelling upon exposure to gastrointestinal fluid, the swelling of the swelling component increasing the dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for an extended period. In some embodiments, the drug dosage form does not include an outer lid connected to the swelling component. In some embodiments, the swelling material of the swelling component forms at least one outer surface of the drug dosage form before the swelling component swells (e.g., in the administered state). The drug may be contained in one or more of the described features of the drug dosage form.

[0044] For illustrative purposes, as shown in Figure 2A, the drug dosage form 200 comprises a first component layer 202 and a swelling component layer 204, the first component layer 202 and the swelling component layer 204 being connected. Figure 2A illustrates the drug dosage form 200 before the swelling component expands. In Figure 2B, after the swelling component 204 expands, the dimensions of the drug dosage form 200 increase compared to the pre-expansion state (e.g., the administered state). In any embodiment described herein, the first component and / or swelling component contains a drug. For example, in some embodiments, the first component contains a drug. As illustrated in Figure 2C, the first component may include a plurality of compartments containing a drug (API), one or more of which have features for controlling the release of the drug from the drug dosage form, such as a plug. As shown in Figure 2C, the first component includes an insoluble shell containing compartments so that the drug is released from a particular embodiment of the drug dosage form. In some embodiments, one or more compartments are configured to release the drug from the drug dosage form in a pulsed manner, for example, the compartments release the drug from there in non-overlapping and / or overlapping series over time. In some embodiments, the drug dosage form includes, for example, a gas-filled compartment to provide buoyancy to the drug dosage form.

[0045] In some embodiments, the drug dosage form comprises a first component, a second component, and a swelling component, the first and second components being connected at least partially via the swelling component, and at least one of the first component, the second component, and the swelling component containing a drug, the first component having a first axis from a first proximal end to a first distal end, the second component having a second axis from a second proximal end to a second distal end, the first and second axes being aligned with each other (in a parallel or substantially parallel manner, for example) when the swelling component is not swollen (e.g., in an administered state), and rotating relative to each other (from a parallel or substantially parallel manner, for example) when the swelling component swells, the swelling component swells when exposed to gastrointestinal fluid, and the swelling of the swelling component or part thereof increases the dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for a longer period of time. In some embodiments, the first axis of the first component and the second axis of the second component become perpendicular to each other when the swelling component swells. In some embodiments, the drug dosage form includes a locking mechanism configured to fix the first and second components in the swollen position of the swelling component. In some embodiments, the first and second components are at least partially connected. In some embodiments, the first and second components are at least partially connected via features such as protrusions or rods of the first and / or second components. In some embodiments, at least a portion of the first component is configured to cooperate with the second component to create a point of rotation. In some embodiments, the first and second components are at least partially connected via a swelling component. The drug may be contained in one or more of the described features of the drug dosage form.

[0046] For illustrative purposes, as shown in Figure 3A, drug dosage form 300 comprises a first component 302, a second component 304, and a swelling component 306, wherein the first component 302 and the second component 304 are connected at least partially via the swelling component 306. In drug dosage form 300, the first component 302 has a first axis 308 from a first proximal end to a first distal end, and the second component 304 has a second axis 310 from a second proximal end to a second distal end. As shown in Figure 3A, when the swelling component is not swollen (e.g., under administration conditions), the first axis 308 and the second axis 310 are aligned with each other (e.g., in a parallel or substantially parallel manner). As shown in Figure 3B, when the swelling component swells, the first axis 308 and the second axis 310 rotate relative to each other (e.g., away from a parallel or substantially parallel configuration) to increase the dimensions of the drug dosage form. In some embodiments, at least one of the first component, the second component, and the swelling component comprises a drug.

[0047] Figure 3C depicts a cross-sectional view of an exemplary drug dosage form similar to those in Figures 3A-3B, where the first and second components are connected, at least partially, via a rod extending from the first component. As shown in Figure 3C, both the first and second components contain a matrix containing the drug (API).

[0048] In some embodiments, the drug dosage form comprises a first component, a second component, and a swelling component, the first and second components being connected at least partially via the swelling component, and at least one of the first component, the second component, and the swelling component containing the drug, the first component having a first axis from a first proximal end to a first distal end, the second component having a second axis from a second proximal end to a second distal end, the swelling component having a central axis, the first and second axes being aligned with each other, points on the first axis and points on the second axis being shifted away from each other as the swelling component swells, the swelling component swells when exposed to gastrointestinal fluid, and the swelling of the swelling component or part thereof increases the dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for an extended period. In some embodiments, the swelling of the swelling component results in the movement of the first component relative to the other components of the drug dosage form. In some embodiments, swelling of the swelling component results in the movement of the first and second components relative to the other components of the drug dosage form. In some embodiments, points on the first axis are shifted away from the central axis of the swelling component, for example, only the points on the first axis are shifted away from the central axis, while the points on the second axis of the second component are not shifted. In some embodiments, points on the first axis and points on the second axis are shifted away from the central axis of the swelling component.

[0049] In some embodiments, the drug dosage form includes a guide track, and the drug dosage form is configured such that a component, such as a first component, slides on the guide track. In some embodiments, the drug dosage form further includes a first guide track and a second guide track, and as the swelling component swells, the first component shifts away from the central axis with the first guide track, and the second component shifts away from the central axis with the second guide track. Generally, such a drug dosage form may have any number of components in addition to the swelling component, such as a first component, a second component, a third component, a fourth component, a fifth component, a sixth component, a seventh component, and an eighth component. In some embodiments, one or more components, including all of them, have a guide track. For example, in some embodiments, the drug dosage form further comprises a third component, a third guide track, a fourth component, and a fourth guide track, wherein when the swelling component swells, the third component shifts away from the central axis together with the third guide track, and the fourth component shifts away from the central axis together with the fourth guide track. The drug may be contained in any one or more of the described features of the drug dosage form.

[0050] In some embodiments, the guide track is configured to prevent the component from leaving the drug dosage form. In some embodiments, the component has features that engage with the guide track. In some embodiments, the swelling of a swellable component pushes the component along the guide track. In some embodiments, the drug dosage form is configured to have features that stop and / or lock the component in place along the guide track.

[0051] For illustrative purposes, as shown in Figure 4A, the drug dosage form 400 comprises a first component 404, a second component 406, and a swelling component 402, wherein the first component 404 and the second component 406 are connected at least partially via the swelling component 402. The first component 404 has a first axis 408 from a first proximal end to a first distal end, the second component 406 has a second axis 410 from a second proximal end to a second distal end, and the swelling component 402 has a central axis. The first axis 408 and the second axis 410 are aligned with each other (for example, on the same line, but alignment as encompassed in this application does not need to be on the same line). Point 412 on the first axis 408, point 414 on the second axis 410, and the central axis of the swelling component 402 are indicated in Figures 4A and 4B to help track the movement of the component during the swelling of the swelling component 402. As shown in Figure 4B, when the swelling component 402 swells, point 412 on the first axis 408 and point 414 on the second axis 410 are shifted away from each other and away from the central axis indicated by the points on the swelling component 402. At least one of the first component, the second component, and the swelling component may contain a drug.

[0052] As shown in Figures 4C and 4D, a drug dosage form may contain multiple components and a swelling component. In Figure 4C, the dosage form includes layers of components and a guide track. As shown in Figure 4D, when the swelling component expands, the components of the drug dosage form expand in the desired direction, resulting in an increase in the overall dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for a longer period of time.

[0053] B. Characteristics of drug dosage forms in an expanded state (e.g., in a gastric state) As described herein, swelling of a swellable component or part thereof increases the dimensions of the drug dosage form, thereby allowing the drug to be retained in the stomach for an extended period. In some embodiments, the swollen state of the drug dosage form is referred to as the gastric retention state. Those skilled in the art will readily understand that the properties of a drug dosage form, such as the size during swelling of a swellable component or part thereof, are dynamic and can change over time. Descriptions of specific states of a drug dosage form, such as the gastric retention state, are not intended to limit the disclosure herein to only one static embodiment of the drug dosage form.

[0054] In some embodiments, when the drug dosage form is in an inflated state (e.g., gastric retention state), the drug dosage form is sized to prohibit and / or prevent the passage of the drug dosage form into the duodenum through the sides of the pyloric region (such as the pyloric sinus, pyloric canal, or pyloric orifice created by the pyloric sphincter). In some embodiments, when the drug dosage form is in an inflated state, the drug dosage form is sized to prohibit and / or prevent the passage of the drug dosage form through the pyloric orifice created by the pyloric sphincter. In some embodiments, when the drug dosage form is in an inflated state, at least two vertical dimensions of the drug dosage form are independently at least about 2 cm to about 7 cm in length, for example, at least about 2 cm to about 5 cm, about 3 cm to about 6 cm, or about 4 cm to about 7 cm in length. In some embodiments, when the drug dosage form is in an expanded state, at least two vertical dimensions of the drug dosage form are independently at least about 2 cm in length, for example, at least about 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm, 5 cm, 5.5 cm, 6 cm, 6.5 cm, or 7 cm in length. In some embodiments, when the drug dosage form is in an expanded state, at least two vertical dimensions of the drug dosage form are independently at least 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm, 5 cm, 5.5 cm, 6 cm, 6.5 cm, or 7 cm in length. In some embodiments, when the drug dosage form is in an expanded state, one of the at least two vertical dimensions is different from the other dimension. In some embodiments, when the drug dosage form is in an expanded state, one of the at least two vertical dimensions is the same as the other dimension.

[0055] The drug dosage forms described herein are configured to remain in the stomach for a longer period of time compared to drug dosage forms that do not have a gastric retention function. In some embodiments, the drug dosage forms are configured to remain in the stomach for about 8 hours to about 7 days, such as about 8 hours to about 24 hours, about 18 hours to about 30 hours, about 20 hours to about 28 hours, about 1 day to about 3 days, or about 3 days to about 7 days. In some embodiments, the drug dosage forms are configured to remain in the stomach for at least about 8 hours, such as at least about 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 31 hours, 32 hours, 33 hours, 34 hours, 35 hours, or 36 hours. In some embodiments, the drug dosage form is configured to remain in the stomach for at least about one day, such as at least two, three, four, five, six, or seven days. In some embodiments, the drug dosage form is configured to remain in the stomach for no more than seven days, such as not exceeding six, five, four, three, two, 36, 30, 24, 18, or 12 hours. In some embodiments, the drug dosage form is configured to remain in the stomach for approximately 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 31 hours, 32 hours, 33 hours, 34 hours, 35 hours, 36 hours, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0056] In some embodiments, the drug dosage form is configured such that the drug dosage form or a portion thereof can pass through the pylorus and be expelled from the stomach. For example, in some embodiments, the first and second components may become disengaged, such as by separating, and then the components of the drug dosage form may be expelled from the stomach. In some embodiments, one or more components of the drug dosage form, such as the first component, the second component, and / or a swelling component, may be eroded or dissolved, either whole or partially, as a result of the drug dosage form being subsequently expelled from the stomach. In some embodiments, the erosion or dissolution of the components or a portion thereof of the drug dosage form is due to prolonged exposure to gastrointestinal fluid in the stomach (for example, prolonged exposure to low pH).

[0057] C. Characteristics of drug dosage forms under different administration conditions The oral drug dosage forms described herein may be formed in any number of shapes, sizes, weights, and appearances. As described herein, the drug dosage forms of this application may take on different characteristics (such as size and shape) during the lifecycle of the administered drug dosage form (e.g., administration state and gastric retention state). Unless otherwise stated, the specific characteristics of the administration states of the drug dosage forms disclosed herein are described below in this section.

[0058] In some embodiments, the drug dosage form is an oral drug dosage form. In some embodiments, the oral drug dosage forms described herein are suitable for oral administration to a human individual. Such drug dosage forms of this application may be any size, shape, or weight suitable for oral administration to a specific human individual, such as a child or an adult. In some embodiments, the drug dosage form is suitable for oral administration to an individual, and the selection of the size, shape, or weight of the drug dosage form is based on one or more of the individual's attributes, such as height, weight, age, or the size of an anatomical feature.

[0059] In some embodiments, the surface, such as the outer surface of the drug dosage form, may have the shape of a capsule, circle, ellipse, bullet, arrowhead, triangle, arc-triangle, square, arc-square, rectangle, arc-rectangle, diamond, pentagon, hexagon, octagon, crescent, almond, or a combination thereof.

[0060] In some embodiments, the drug dosage form has a maximum transverse dimension of approximately 5 mm to approximately 20 mm, such as approximately 5 mm to approximately 15 mm, approximately 6 mm to approximately 13 mm, or approximately 7 mm to approximately 11 mm. In some embodiments, the drug dosage form has a maximum transverse dimension of at least approximately 5 mm, such as at least approximately 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm. In some embodiments, the drug dosage form has a maximum transverse dimension of less than approximately 20 mm, such as less than approximately 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, or 5 mm. In some embodiments, the drug dosage form has a maximum cross-sectional dimension of approximately 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm. In some embodiments, the maximum cross-sectional dimension is measured across a surface, such as the outer surface of the drug dosage form. In some embodiments, the maximum cross-sectional dimension is measured across the drug dosage form.

[0061] In some embodiments, the drug dosage form has a transverse dimension perpendicular to a maximum transverse dimension of approximately 5 mm to approximately 20 mm, such as approximately 5 mm to approximately 15 mm, approximately 6 mm to approximately 13 mm, or approximately 7 mm to approximately 11 mm. In some embodiments, the drug dosage form has a transverse dimension perpendicular to a maximum transverse dimension of at least approximately 5 mm, such as at least approximately 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm. In some embodiments, the drug dosage form has a transverse dimension perpendicular to a maximum transverse dimension of less than approximately 20 mm, such as less than approximately 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, or 5 mm. In some embodiments, the drug dosage form has a transverse dimension perpendicular to one of the largest transverse dimensions, which is approximately 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm. In some embodiments, the transverse dimension perpendicular to the largest transverse dimension is measured across the surface of the delayed-release oral drug dosage form. In some embodiments, the transverse dimension perpendicular to the largest transverse dimension is measured across the drug dosage form.

[0062] In some embodiments, the drug dosage form has a thickness of approximately 5 mm to approximately 20 mm, such as approximately 5 mm to approximately 15 mm, approximately 6 mm to approximately 13 mm, or approximately 7 mm to approximately 11 mm. In some embodiments, the drug dosage form has a thickness of at least approximately 5 mm, such as at least approximately 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm. In some embodiments, the drug dosage form has a thickness of less than approximately 20 mm, such as less than approximately 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, or 5 mm. In some embodiments, the drug dosage form has a thickness of approximately 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm.

[0063] In some embodiments, the drug dosage form has a total weight of approximately 50 mg to approximately 1,000 mg, such as approximately 50 mg to approximately 100 mg, approximately 100 to approximately 200 mg, approximately 200 mg to approximately 300 mg, approximately 300 mg to approximately 400 mg, approximately 400 mg to approximately 500 mg, approximately 500 mg to approximately 600 mg, approximately 600 mg to approximately 700 mg, approximately 700 mg to approximately 800 mg, approximately 800 mg to approximately 900 mg, or approximately 900 mg to approximately 1,000 mg. In some embodiments, the drug dosage form has a total weight of at least about 50 mg, such as at least about 75 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or 1,000 mg. In some embodiments, the drug dosage form has a total weight of less than approximately 1,000 mg, such as about 950 mg, 900 mg, 850 mg, 800 mg, 750 mg, 700 mg, 650 mg, 600 mg, 550 mg, 500 mg, 475 mg, 450 mg, 425 mg, 400 mg, 375 mg, 350 mg, 325 mg, 300 mg, 275 mg, 250 mg, 225 mg, 200 mg, 175 mg, 150 mg, 125 mg, 100 mg, 75 mg, or less than 50 mg. In some embodiments, the drug dosage form has a total weight of approximately 50 mg, 75 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or 1,000 mg.

[0064] D. Drug integration in drug dosage forms and drug release profiles The drug dosage forms described herein comprise one or more drugs. The drugs in a drug dosage form may be released at any point in the drug dosage form's life cycle. For example, in some embodiments, a drug dosage form is formulated to release the drug when it is in an expanded state (e.g., a gastric retained state). In some embodiments, substantially all of the drug in the drug dosage form, such as at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100%, is released while in an expanded state (e.g., a gastric retained state). In some embodiments, a drug dosage form is configured to release the drug before the swelling of the swelling component. In some embodiments, a drug dosage form is configured to release the drug after it has left the stomach.

[0065] In some embodiments, the drug is a poorly water-soluble drug. In some embodiments, the poorly water-soluble drug is a Biopharmaceutical Classification System (BCS) Class II active pharmaceutical ingredient (API), such as a drug having high permeability and low solubility. In some embodiments, the drug is selected from the group consisting of aceclofenac, bicalutamide, carbamazepine, carvedilol, clotrimazole, cinnarizine, danazol, dapsone, estradiol, essetimibe glibenclamide, fenofibrate, griseofulvin, ibuprofen, itraconazole, ketoconazole, mefenamic acid, naproxen, nevirapine, nifedipine, nitrofurantoin, nomegestrolacetate, phenytoin sodium salt, piroxam, praziquantel, rifampicin, sulfamethoxazole, trimethoprim, and verapamil hydrochloride.

[0066] A drug dosage form may be configured to release a drug based on any desired release profile. Generally, the drug dosage forms described herein are designed to remain in the stomach for an extended period, so the release profile of at least one drug is configured based on the expected gastric retention of the drug dosage form. In some embodiments, when two or more drugs are present in a drug dosage form, the drug dosage form is configured to release each drug according to a desired release profile. In some embodiments, the drug dosage form is configured so that all (or substantially all, such as at least about 90%) of the drug contents within the drug dosage form are released during the expected gastric retention of the drug dosage form. In some embodiments, the drug dosage form is configured so that a certain amount of drug contents within the drug dosage form (such as a second drug) is released after the drug dosage form or its components are expected to be expelled from the stomach. In some embodiments, drug dosage forms are formulated and configured so that the drug is released according to a delayed-release profile, a sustained-release profile, a delayed-sustained-release profile, a zero-order-release profile, a primary-release profile, an immediate-release profile plus a sustained-release profile, an immediate-release profile plus a delayed-release profile, an immediate-release profile plus a delayed-sustained-release profile, a pulsed-release profile, a repeated-pulsed-release profile, an immediate-release profile plus a pulsed-release profile, or a combination thereof. For example, in some embodiments, a delayed-release profile includes the release of the drug at least about two hours after administration of the drug dosage form to an individual. In some embodiments, a sustained-release profile includes the release of the drug for a period exceeding about two hours.

[0067] The drug dosage forms described herein can be formulated and configured using various techniques to release the drug according to a desired drug release profile. In some embodiments, the release of the drug from the drug dosage form is based on the erosion of the drug-containing material, such as when the drug-containing material is exposed to gastrointestinal fluid. In some embodiments, the drug-containing material is configured as a layer having a predetermined surface area, thickness, and drug mass fraction, such as the surface area exposed to gastrointestinal fluid, and these properties of the drug-containing material provide the desired drug release. In some embodiments, the drug-containing material is in the form of a multilayer structure. In some embodiments, the drug-containing material is embedded in a material of a component, such as a first component or a swelling component of the drug dosage form. Designs, configurations, and materials of such drug-containing materials that provide a desired drug release are known in the art; see, for example, U.S. Patent No. 10,350,822, which is incorporated in whole herein.

[0068] In some embodiments, the drug dosage form comprises a drug-containing compartment, the compartment having an orifice from which the drug is released. In some embodiments, the orifice is blocked by an erosive material such as a plug. In some embodiments, the feature of blocking the orifice so that the drug is retained within the compartment of the drug dosage form is configured so that the orifice is no longer blocked at a desired time. For example, in some embodiments, the drug-containing compartment is sealed with an erosive plug, the erosive plug dissolves at a specific time after administration to the individual, thereby releasing the drug from the drug dosage form. The timing of release may be based, for example, on the thickness of the plug and / or the material of the plug. The drug-containing compartment may consist of a first component of the drug dosage form or any component such as a swelling component. In some embodiments, the drug dosage form comprises multiple drug-containing compartments. In some embodiments, the component is a non-erosive material such as an insoluble shell material. In some embodiments, the component is eroded after the drug has left the drug-containing compartment, for example, after the drug dosage form has left the stomach.

[0069] In some embodiments, the drug dosage form is configured so that the drug leaches out of its material.

[0070] The drugs or drug formulations described herein may be part of any of the components described herein.

[0071] In some embodiments, the drug dosage form includes a first component containing a drug. In some embodiments, the drug dosage form includes a second component containing a drug. In some embodiments, the drug dosage form includes a third component containing a drug. In some embodiments, the drug dosage form includes a fourth component containing a drug. In some embodiments, the drug dosage form includes a swelling component containing a drug. In some embodiments, the swelling agent of the swelling component contains a drug. In some embodiments, the drug dosage form includes multiple components containing a drug, each component containing the same drug, and / or two or more components containing the same drug. In some embodiments, the drug dosage form includes multiple components containing a drug, each component containing a different drug, and / or two or more components containing different drugs. In some embodiments, the swelling component does not contain a drug.

[0072] B. Materials of drug dosage forms The materials used to form the components of the drug dosage form, such as the first component and the swelling component, may be selected based on the desired properties and / or functions.

[0073] In some embodiments, a swelling component, or a portion thereof, such as a swelling agent, is configured and formulated to swell to a desired size and / or shape when exposed to gastrointestinal fluid. In some embodiments, the swelling component forms a predetermined shape when swollen. In some embodiments, the shape of the swelling component after swelling is different from the shape of the swelling component before swelling. In some embodiments, the shape of the swelling component after swelling is the same as the shape of the swelling component before swelling. In some embodiments, the swelling component includes a coating. In some embodiments, the coating of the swelling component delays the swelling of the swelling component for at least a predetermined amount of time after administration of the drug dosage form to an individual, such as by prohibiting contact with gastrointestinal fluid and / or inhibiting swelling.

[0074] In some embodiments, the swelling component and its material are configured to expand at a desired rate and / or with a desired force. For example, in some embodiments, the swelling component and its material are configured to expand rapidly upon contact with the gastrointestinal tract to prevent the drug dosage form from passing through the stomach before remaining in the stomach for a desired gastric retention period. In some embodiments, the swelling component and its material are configured to expand to a gastric retention state within about 5 minutes after contact with gastrointestinal fluid, for example, within about 4.5 minutes, 4 minutes, 3.5 minutes, 3 minutes, 2.5 minutes, 2 minutes, 1.5 minutes, 1 minute, or 30 seconds. In some embodiments, the swelling component and its material are configured to expand with the force necessary to move the components of the drug dosage form to a gastric retention state.

[0075] In some embodiments, the swelling component includes a gas generator such as a foaming agent. In some embodiments, the gas generator includes a carbon dioxide source. In some embodiments, the gas generator includes a carbonate, or a bicarbonate, or a combination thereof. Exemplary carbonates include, but are not limited to, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, calcium carbonate, calcium bicarbonate, magnesium carbonate, and magnesium bicarbonate. In some embodiments, the gas generator is sodium bicarbonate. In some embodiments, the swelling component further includes an acid or an acid source. Exemplary acids or acid sources include, but are not limited to, citric acid or its salts, tartaric acid or its salts, fumaric acid or its salts, adipic acid or its salts, malic acid or its salts, and formic acid, sorbic acid, succinic acid or its salts, glacial acetic acid, salicylic acid, propionic acid, phosphoric acid or its salts, lactic acid, and benzoic acid. In some embodiments, the acid source is sodium formate. In some embodiments, the swelling component includes sodium bicarbonate and sodium formate.

[0076] In some embodiments, the swelling component, for example, the swelling agent for the swelling component, includes a material selected from the group consisting of crosslinking products and shape memory materials. In some embodiments, the swelling component, for example, the swelling agent of the swelling component, is polyethylene oxide-polyethylene glycol (PEO-PEG) crosslinked polymer, polycaprolactone-polyethylene glycol-polycapractone (PCL-PEG-PCL), hydroxypropyl cellulose, polyethylene oxide (PEO), for example, high molecular weight PEO, sodium alginate, carbomer, high molecular weight hydroxypropyl cellulose (HPC), high molecular weight hydroxypropyl methylcellulose or hypromeros (HPMC), methylcellulose (MC), high molecular weight polyvinyl alcohol (PVA), polyvinyl acetate (PVAc) and polyvinylpyridron (PVP) 80 / 20, methacrylate ester copolymer, poly[butyl methacrylate, (2-dimethylaminoethyl) methacrylate, methyl methacrylate] in a ratio of 1:2:1 (for example, EUDRAGIT® E 100, EUDRAGIT® E 12,5, EUDRAGIT® E Poly[ethyl acrylate, methyl methacrylate] ratio 2:1 (e.g., EUDRAGIT® NE 30 D, EUDRAGIT® NE 40 D, EUDRAGIT® NM 30 D), poly[methacrylic acid, methyl methacrylate] ratio 1:1 (e.g., EUDRAGIT® L 100, EUDRAGIT® L 12.5, EUDRAGIT® L 12.5 P), poly[methacrylic acid, ethyl acrylate] ratio 1:1 (e.g., Acrylic-EZE, Acrylic-EZE93A, Acrylic-EZE MP, EUDRAGIT® L 30 D-55, EUDRAGIT® L 100-55, Eastacryl® 30 D, Kollicoat® MAE 30 DP, Kollicoat® MAE 100) P), poly[methacrylic acid, methyl methacrylate] ratio 1:2 (for example, EUDRAGIT(registered trademark) S 100, EUDRAGIT(registered trademark) S 12.5, EUDRAGIT(registered trademark) 12,5P, poly[methyl acrylate, methyl methacrylate, methacrylic acid] ratio 7:3:1) (e.g., EUDRAGIT® FS 30 D), poly[ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate] ratio 1:2:0.2 (e.g., EUDRAGIT® RL 100, EUDRAGIT® RLPO, EUDRAGIT® RL 30 D, EUDRAGIT® RL 12,5), poly[ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate] ratio 1:2:0.1 (e.g., EUDRAGIT® RS 100, EUDRAGIT® RS PO, EUDRAGIT® RS 30 D, EUDRAGIT® RS 12,5) The material includes a material selected from the group consisting of hydroxypropyl methylcellulose acetate succinate or hypromellose acetate succinate (HPMCAS), hydroxypropyl methylcellulose phthalate (HPMCP), or a combination thereof. In some embodiments, the shape memory material includes a block copolymer of polyurethane, polyethylene terephthalate (PET) and polyethylene oxide (PEO), a block copolymer containing polystyrene and poly(1,4-butadiene), an ABA triblock copolymer made from poly(2-methyl-2-oxazoline) and polytetrahydrofuran, polynorbornene (Norsorex, developed by CdF Chemie / Nippon Zeon), polynorbornene having partially substituted polyphedral oligosylquioxane (POSS), polycyclooctene (PCOE) and poly(5-norbornene-exo, exo-2,A composite material consisting of a copolymer of 3-dicarboxylic acid anhydride (PNBEDCA), poly(ester urethane), polyol (soft segment), and diisocyanate bonded with a chain extender (hard phase) (poly(ε-caprolactone) (PCL), poly(ethylene adipate) (PEA) glycol), a combination of poly(ester urethane) (PUR) and PCL, ethylene oxide-ethylene terephthalate segment copolymer, oligo(ε-caprolactone) and oligo(p-dioxanone) based PUR, poly(p-dioxanone)-b-poly(tetramethylene oxide glyco The material is selected from the group consisting of multiblock copolymers, poly(methyl methacrylate)-poly(ethylene glycol) (PMMA-PEG) semi-interpenetrating networks (IPN), poly(cyclohexyl methacrylate) (PCHMA) whose main chain is crosslinked with a bifunctional PCL polymer, polymers in which short PEG side chains are grafted onto a PCL main chain, Nafion®, copolymer (ester urethane) networks, covalently crosslinked poly[ethylene-co-(vinyl acetate)] (cPEVA), combinations of PCL and poly(tetramethylene ether) glycol (PTMEG), or combinations thereof. In some embodiments, the material may have multiple properties, including swelling properties and shape memory properties.

[0077] In some embodiments, the components, such as the first component, include insoluble materials, pH-sensitive erosion materials, such as materials not eroded by the pH of the stomach, materials that are gradually eroded, such as drug dosage forms, or materials that are eroded after the component has left the stomach, or a combination thereof. In some embodiments, components such as the first component may be poly[butyl methacrylate, (2-dimethylaminoethyl) methacrylate, methyl methacrylate] in a ratio of 2:1 (e.g., EUDRAGIT® E 100, EUDRAGIT® E 12,5, EUDRAGIT® E PO), poly[ethyl acrylate, methyl methacrylate] in a ratio of 2:1 (e.g., EUDRAGIT® NE 30 D, EUDRAGIT® NE 40 D, EUDRAGIT® NM 30 D), poly[methacrylic acid, methyl methacrylate] in a ratio of 1:1 (e.g., EUDRAGIT® L 100, EUDRAGIT® L 12,5, EUDRAGIT® L 12,5 P), or poly[methacrylic acid, ethyl acrylate] in a ratio of 1:1 (e.g., Acryl-EZE, Acryl-EZE93A, Acryl-EZE MP, EUDRAGIT® L 30 D-55, EUDRAGIT® L 100-55, Eastacryl® 30 D, Kollicoat® MAE 30 DP, Kollicoat® MAE 100 P), Poly[methacrylic acid, methyl methacrylate] ratio 1:2 (e.g., EUDRAGIT® S 100, EUDRAGIT® S 12.5, EUDRAGIT® 12.5 P), Poly[methyl acrylate, methyl methacrylate, methacrylic acid] ratio 7:3:1 (e.g., EUDRAGIT® FS 30 D), Poly[ethyl acrylate, methyl methacrylate, trimethylammonium methacrylate] ratio 1:2:0.2 (e.g., EUDRAGIT® RL 100, EUDRAGIT® RLPO, EUDRAGIT® RL 30 D, EUDRAGIT (registered trademark) RL 12,5), poly[ethyl acrylate, methyl methacrylate, trimethylammonium methacrylate] ratio 1:2:0.The material comprises a material selected from the group consisting of 1 (e.g., EUDRAGIT® RS 100, EUDRAGIT® RS PO, EUDRAGIT® RS 30 D, EUDRAGIT® RS 12, 5), stearic acid, ethylcellulose (EC), titanium dioxide, cellulose phthalate acetate (CAP), poly(lactide-co-glycolide) (PLGA), ethylene vinyl acetate copolymer, polyethylene (PE), polycaprolactone (PCL), polylactic acid (PLA), cellulose butyrate acetate (CAB), cellulose acetate (CA), polyvinyl acetate (PVAc), polyvinyl acetal diethylaminolactate (AEA), or combinations thereof.

[0078] In some embodiments, the drug-form material is a thermoplastic material. In some embodiments, the thermoplastic material is a thermoplastic polymer. In some embodiments, the thermoplastic material comprises a plasticizer and one or more other additives, such as fillers, binders, lubricants, flow promoters, and disintegrants. In some embodiments, the additive is selected from the group consisting of clay, SiC nanoparticles, Ni powder, carbon nanotubes, carbon fibers, carbon black, graphene, metal oxides (e.g., Fe3O4, TiO2, ZnO), silver (Ag) nanoparticles, gold (Au) nanoparticles, silver and gold nanoparticles, nanorods, nanowhiskers, nanowires, and cellulose nanocrystals.

[0079] E. Characteristics of additional drug dosage forms In some embodiments, the drug dosage form includes a gas-filled compartment to provide buoyancy to the drug dosage form, for example. In some embodiments, the gas-filled compartment is embedded in a component such as a first component or a swelling component. In some embodiments, the gas-filled compartment has an erosive plug, which is configured to open the gas-filled compartment after the drug dosage form has been administered to the individual.

[0080] In some embodiments, the drug dosage form includes additional features such as an outer coating, outer layer, or outer marking. In some embodiments, the outer coating or layer is a flavor coating. In some embodiments, the outer coating or layer is a sugar coating. In some embodiments, the outer coating or layer is a cosmetic coating. In some embodiments, the outer coating or layer is a color coating. In some embodiments, the outer coating or layer is a film coating. In some embodiments, the outer coating or layer is a polymer coating. In some embodiments, the outer coating completely encloses the drug dosage form. In some embodiments, the outer layer forms part of the exterior of the drug dosage form. In some embodiments, additional components are labels such as a drug logo, company name or abbreviation, graphics, drug label, drug chemical name or abbreviation, drug specifications, identification barcode, or a combination thereof.

[0081] III. Commercial batches In some embodiments, what is provided herein is a commercially available batch of the drug dosage forms described herein. In some embodiments, the commercially available batch contains at least about 100, 150, 200, 250, 500, 750, 1,000, 2,500, 5,000, 7,500, 10,000, 20,000, 30,000, 40,000, 50,000, 60,000, 70,000, 80,000, 90,000, or 100,000 of the delayed-release oral drug dosage forms described herein. In some embodiments, each of the drug dosage forms in the commercially available batch is manufactured using the same technique, such as via three-dimensional (3D) printing.

[0082] In some embodiments, a commercially available batch has a standard deviation of about 0.1 or less, for example, 0.05 or less, for one or more of the following: the amount of drug in the drug dosage form, the weight of the drug dosage form, the dimensions of the drug dosage form (such as in the administration state and / or holding state), and the gastric retention time of the drug dosage form. In some embodiments, the dimensions of the drug dosage form are the maximum cross-sectional dimensions of the oral drug dosage form (such as in the administration state) before swelling of the swelling component. In some embodiments, the dimensions of the drug dosage form are the cross-sectional dimensions perpendicular to the maximum cross-sectional dimensions of the oral drug dosage form (such as in the administration state) before swelling of the swelling component. In some embodiments, the dimensions of the drug dosage form are the maximum cross-sectional dimensions of the oral drug dosage form (such as in the gastric retention state) after swelling of the swelling component. In some embodiments, the dimensions of the drug dosage form are the cross-sectional dimensions perpendicular to the maximum cross-sectional dimensions of the oral drug dosage form (such as in the gastric retention state) after swelling of the swelling component.

[0083] IV. Manufacturing Method In some embodiments, what is provided herein is a method for producing the drug dosage forms described herein. In some embodiments, the production method includes a three-dimensional (3D) printing technique for forming at least one of the components or parts thereof of the drug dosage forms described herein.

[0084] As used herein, “printing,” “three-dimensional printing,” “3D printing,” “additive manufacturing,” or their equivalents refer to the process of producing three-dimensional objects, such as delayed-release oral drug dosage forms, layer by layer using digital design. The basic processes of three-dimensional printing are described in U.S. Patents 5,204,055, 5,260,009, 5,340,656, 5,387,380, 5,503,785, and 5,633,021. Additional U.S. patents and patent applications relating to three-dimensional printing include: U.S. Patents No. 5,490,962, No. 5,518,690, No. 5,869,170, No. 6,530,958, No. 6,280,771, No. 6,514,518, No. 6,471,992, No. 8,828,411, U.S. Publications 2002 / 0015728, 2002 / 0106412, 2003 / 0143268, 2003 / 0198677, and 2004 / 0005360. The contents of the above U.S. patents and patent applications are incorporated herein by reference in their entirety. In some embodiments, additive manufacturing techniques are used to produce the drug dosage forms described herein. In some embodiments, layer-by-layer techniques are used to produce the drug dosage forms described herein. For example, in some embodiments, the layer-by-layer technique includes extruding one or more materials for a first layer of the drug dosage form, and then proceeding to extrude one or more materials for a second layer of the drug dosage form. In some embodiments, the layers, such as the first or second layer, are cross-sections of the drug dosage form. In some embodiments, the layers, such as the first or second layer, contain a portion of the first component and a portion of the swelling component of the drug dosage form. Because 3D printing can handle a range of pharmaceutical materials and allows for localized control of both composition and architecture, 3D printing is suitable for manufacturing drug dosage forms having complex geometric shapes and compositions according to the present invention.

[0085] In some embodiments, when used in relation to components of a drug dosage form, for example, a swelling component, the layer refers to the composition of the components of the drug dosage form and may include multiple printed layers of the same material. In some embodiments, the layer has a predetermined packing density, such as a three-dimensionally printed packing density. In some embodiments, the layer includes multiple printed layers ranging from about 5 to about 2500, such as about 10 to about 2500 printed layers, about 25 to about 100 printed layers, about 50 to about 200 printed layers, about 100 to about 200 printed layers, about 150 to about 250 printed layers, about 200 to about 250 printed layers, about 500 to about 1000 printed layers, or about 2000 to about 2400 printed layers. In some embodiments, the thickness of the printed layer is about 5 mm or less, for example, about 4 mm, 3 mm, 2 mm, 1 mm, 0.9 mm, 0.8 mm, 0.7 mm, 0.6 mm, 0.5 mm, 0.4 mm, 0.3 mm, 0.2 mm, 0.1 mm, 0.09 mm, 0.08 mm, 0.07 mm, 0.06 mm, 0.05 mm, 0.04 mm, 0.03 mm, 0.02 mm, or 0.01 mm or less. In some embodiments, the thickness of the printed layer is approximately 5 mm, 4 mm, 3 mm, 2 mm, 1 mm, 0.9 mm, 0.8 mm, 0.7 mm, 0.6 mm, 0.5 mm, 0.4 mm, 0.3 mm, 0.2 mm, 0.1 mm, 0.09 mm, 0.08 mm, 0.07 mm, 0.06 mm, 0.05 mm, 0.04 mm, 0.03 mm, 0.02 mm, or 0.01 mm.

[0086] From the perspectives of raw materials, equipment, and solidification, various 3D printing methods have been developed for manufacturing. These 3D printing methods include binder deposition (see Gibson et al., Additive Manufacturing Technologies: 3D Printing, Rapid Prototyping, and Direct Digital Manufacturing, 2nd ed. Springer, New York, 2015; Katstra et al., Oral dosage forms fabricated by three-dimensional printing, J Control Release, 66, 2000; Katstra et al., Fabrication of complex oral delivery forms by three-dimensional printing, Dissertation in Materials Science and Engineering, Massachusetts Institute of Technology, 2001; Lipson et al., Fabricated: The New World of 3D printing, John Wiley & Sons, Inc., 2013; Jonathan, Karim, 3D printing in pharmaceutics: a new tool for designing customized drug delivery systems, Int J Pharm, 499, 2016), and material ejection (see Jonathan, Karim, 3D printing in pharmaceutics: a new tool for designing customized drug delivery systems, Int J (See Pharm, 499, 2016), extrusion (Gibson et al., Additive Manufacturing Technologies: 3D Printing, Rapid Prototyping, and Direct Digital Manufacturing. 2nd ed.)This includes methods such as Springer, New York, 2015, and photopolymerization (see Melchels et al., A review on stereolithography and its application in biomedical engineering. Biomaterials, 31, 2010).

[0087] In some embodiments, the drug dosage forms described herein are 3D printed using an extrusion method. In some embodiments, the 3D printing method includes using a double-screw extrusion method. In the extrusion process, the material is extruded through a printing nozzle from a robot-operated print head. Unlike binder deposition, which requires a powder bed, the extrusion method can print on any substrate. A variety of materials, including thermoplastic materials, pastes and colloidal suspensions, silicones, and other semi-solids disclosed herein, can be extruded for three-dimensional printing. One extrusion printing method is molten extrusion deposition (MED), which uses the extruded material from the print head to print layers of material to form components of the drug dosage form. Another common type of extrusion printing is fusion deposition modeling, which uses a solid polymer filament for printing. In fusion deposition modeling, a gear system drives the filament into a heated nozzle assembly for extrusion (see Gibson et al., Additive Manufacturing Technologies: 3D Printing, Rapid Prototyping, and Direct Digital Manufacturing, 2nd ed. Springer, New York, 2015).

[0088] In some embodiments, 3D printing is performed by melt extrusion deposition (MED). In some embodiments, the melt extrusion deposition technique includes preparing the material to be extruded, such as by preparing a powder in a hot melt extruder, and then feeding the material to a MED printhead. The MED printhead then extrudes the material to form a delayed-release oral drug dosage form in an additive manner (layer-by-layer deposition). In some embodiments, each material of the drug dosage form, such as a first component and a swelling component, is extruded from a different MED printhead. In some embodiments, the MED printhead extrudes the material according to instructions compliant with one or more gcode files. Exemplary MED techniques are disclosed, for example, in WO2019 / 137333, WO2018 / 137686, and U.S. Patent No. 10,201,503, each of which is incorporated herein by reference in whole.

[0089] In some embodiments, 3D printing is performed by fused deposition modeling (FDM). In some embodiments, three-dimensional printing is performed by fused extrusion deposition or hot melt extrusion combined with a 3D printing technique such as FDM. In some embodiments, 3D printing is performed by non-filament FDM. In some embodiments, 3D printing is performed by inkjet printing. In some embodiments, 3D printing is performed by selective laser sintering (SLS). In some embodiments, 3D printing is performed by stereolithography (SLA or SL). In some embodiments, 3D printing is performed by PolyJet, Multi-Jet Printing System (MJP), Perfactory, Solid Object Ultraviolet-Laser Printer, Bioplotter, 3D Bioprinting, Rapid Freeze Prototyping, Benchtop System, Selective Deposition Lamination (SDL), Laminated Object Manufacturing (LOM), Ultrasonic Consolidation, ColorJet Printing (CJP), EOSINT Systems, Laser Engineered Net Shaping (LENS), and Aerosol Jet System, Electron Beam Melting (EBM), Laser CUSING (registered trademark), Selective Laser Melting (SLM), Phenix PX™ Series, Microsintering, Digital Part Materialization (DPM), or VX System.

[0090] In some embodiments, the 3D printing method described herein includes a continuous feeding method. In some embodiments, the 3D printing method described herein includes a batch feeding method.

[0091] In some embodiments, the method for producing the drug dosage forms described herein includes other methods, such as a combination of injection molding and 3D printing, and 3D printing techniques such as 3D printing.

[0092] The method instructions for 3D printing the drug dosage forms disclosed herein may be generated in a variety of ways, including direct coding, derivation from solid CAD models, or other means specific to the computer interface and application software of the 3D printer. These instructions may include information regarding the number and spatial arrangement of droplets, as well as information regarding general 3D printing parameters such as the drop spacing in each linear dimension (X, Y, Z) and the volume or mass of fluid per droplet. For a given set of materials, these parameters may be adjusted to refine the quality of the structure created. The overall resolution of the structure created is a function of powder particle size, fluid droplet size, printing parameters, and material properties.

[0093] In some embodiments, one or more components of a drug dosage form are manufactured separately, such as being printed separately, and then assembled to form the drug dosage form. In some embodiments, all components of a drug dosage form are manufactured in a single manner, such as being printed in a single manner, without requiring subsequent assembly.

[0094] The drug dosage forms and their components described in this application can be printed on a commercial scale. For example, in some embodiments, 10,000 to 100,000 units of drug dosage forms can be 3D printed per hour using the methods disclosed herein. In some embodiments, 10,000 to 100,000 drug dosage forms can be 3D printed per hour using the methods disclosed herein. In some embodiments, 10,000 to 100,000 units of medication can be 3D printed per hour using the methods disclosed herein. In some embodiments, 10,000 to 100,000 units of medication can be 3D printed per hour using the methods disclosed herein.

[0095] In some embodiments, the materials used to print the drug dosage form and dosing unit, or its components, such as a precursor drug dosage form, are each ejected by different print heads. For example, in some embodiments, the swelling agent of a swelling component is printed by a first print head, the lid of the swelling component is printed by a second print head, and the first component is printed by a third print head.

[0096] The 3D printing methods described herein include printing materials in any order that enables the production of oral drug dosage forms and dosing units or their components, for example, precursor drug dosage forms disclosed herein.

[0097] In some embodiments, the 3D printing method includes designing a drug dosage form or dosing unit, or its components, such as a precursor drug dosage form, entirely or partially, on a computer system. In some embodiments, the method includes inputting parameters of a desired drug release profile and / or oral drug dosage form and / or dosing unit and / or precursor drug dosage form into a computer system. In some embodiments, the method includes providing one or more parameters to be printed, such as layer surface area, thickness, drug mass fraction, and erosion rate. In some embodiments, the method includes providing a desired drug release profile. In some embodiments, the method includes creating a virtual image of the item to be printed. In some embodiments, the method includes creating a computer model that includes predetermined parameters. In some embodiments, the method includes supplying predetermined parameters to a 3D printer and printing the item according to such predetermined parameters. In some embodiments, the method includes creating a 3D drawing of the item to be printed based on predetermined parameters, the 3D drawing being created on a computer system. In some embodiments, the method includes converting a 3D drawing, such as a slice, into a 3D printing code, such as G-code. In some embodiments, the method involves using a computer system to execute a 3D printing code, thereby printing according to the method described herein.

[0098] V. Methods for delivering drugs to individuals In some embodiments, methods are provided for delivering a drug into an individual and allowing the drug to remain in the individual's stomach for an extended period, the method comprising orally administering a drug dosage form described herein to the individual. In some embodiments, the drug dosage form is configured to remain in the individual's stomach for an extended period (e.g., at least about 24 hours). In some embodiments, the drug may be released from the drug dosage form at a predetermined time after administration to the individual. For example, in some embodiments, the drug is released in the individual's stomach at least about 12 hours after administration of the drug dosage form to the individual.

[0099] Those skilled in the art will recognize that several embodiments are possible within the scope and spirit of the disclosure of this application. The disclosure is further illustrated by the following embodiments, which should not be construed as limiting the disclosure in scope or spirit to the specific procedures described herein. [Examples]

[0100] Example 1 This example demonstrates the design and testing of a 3D printed drug dosage form configured for gastric retention. The drug dosage form contained two swelling components, each containing a swelling agent and an outer lid, the outer lid forming the opposing surfaces of the drug dosage form (Figures 1E and 1F). The outer lid was configured to open outward after swelling of the swelling agent using a hinge mechanism. The swelling components were enclosed by a shell forming the first component of the drug dosage form. Three configurations of the drug dosage form were prepared and tested as follows:

[0101] Preparation of materials Materials for printing shell and swelling components were prepared as follows: The printing components were mixed according to the desired preset ratios and added to a heated torque rheometer, where they were melted together. The mixture was then removed from the torque rheometer and was ready for use.

[0102] The shell material and outer lid of the swelling component were made of EUDRAGIT® RSPO (RSPO). The swelling agent of the swelling component contained ammonium methacrylate copolymer, polyethylene glycol molecular weight 400 (PEG400), and sodium carbonate or sodium alginate, as shown in Table 1.

[0103] Printing method Three exemplary drug dosage forms (indicated as A, B, and C) based on the designs in Figures 1E and 1F were printed and tested for their swelling properties. Different print fill densities were tested to evaluate the printing of the drug dosage forms. The shell fill density was set to 100%. The outer lid fill densities were set to 100%, 50%, or 30%. The swelling agent fill densities were set to 100%, 50%, or 30%.

[0104] Each layer of each component was 3D printed using concentric circles, lines, or a grid. Different materials, infill rates, and printing modes (concentric circles, lines, or grid) can be combined.

[0105] Table 1 shows the composition, filling mode, filling rate, and dimensions of drug dosage forms A, B, and C. [Table 1]

[0106] Swelling properties of the fabricated drug dosage form Dosage forms A, B, and C were subjected to water and an aqueous solution with a pH of 1.2 to test their swelling properties. The dimensions of A, B, and C were measured after swelling for 1 hour and 2 hours under both conditions, and the results are reported in Table 2.

[0107] All three dosage forms showed a significant increase in their height at pH 1.2 and in water, with dosage form B exhibiting the greatest increase under both conditions. The increase at pH 1.2 was lower for dosage forms A and B than in water, but comparable for dosage form C under both conditions. These results demonstrate the possibility of fine-tuning the size of the swollen dosage form through a combination of design choices (composition, packing density, outer cap dimensions, etc.), enabling the achievement of desired swelling characteristics with high precision. [Table 2]

Claims

1. A drug dosage form comprising a first component and a swelling component, The first component and the swelling component are connected, At least one of the first component and the swelling component contains a drug, The aforementioned swelling component or a part thereof swells when exposed to gastrointestinal fluid, A drug dosage form in which the swelling of the swelling component or a portion thereof increases the dimensions of the drug dosage form, thereby enabling the drug to be retained in the stomach for at least about 24 hours.

2. The drug dosage form according to claim 1, wherein the swelling component comprises an outer lid and a swelling agent, the outer lid is connected to the swelling agent, and the outer lid is configured to form at least a portion of the outer surface of the drug dosage form.

3. The drug dosage form according to claim 2, wherein the surface of the outer lid and a portion of the first component form the outer surface of the drug dosage form.

4. The drug dosage form according to claim 2 or 3, wherein a portion of the outer lid is operably connected to the dosage form such that the outer lid moves outward from the drug dosage form on a hinge due to the swelling of the swelling component.

5. The drug dosage form according to claim 2 or 3, wherein the outer lid is configured such that the swelling of the swelling component causes the entire outer lid to move outward from the drug dosage form.

6. A drug dosage form according to any one of claims 2 to 5, each further comprising one or more swelling components including an outer lid.

7. The drug dosage form according to claim 1, wherein the swelling component and the first component are configured as two separate layers.

8. The drug dosage form according to claim 1, further comprising a second component, wherein the first component and the second component are connected at least partially via the swelling component.

9. The drug dosage form according to claim 8, wherein the swelling of the swelling component shifts the relative positions of the first component and the second component, thereby increasing the dimensions of the drug dosage form.

10. The drug dosage form according to claim 8 or 9, wherein the first component has a first axis from a first proximal end to a first distal end, the second component has a second axis from a second proximal end to a second distal end, the swellable component has a central axis, and when the swellable component swells, the first axis and the second axis are shifted relative to each other.

11. The drug dosage form according to claim 10, wherein the first axis and the second axis are aligned with each other when the swelling component is not swollen, and rotate relative to each other when the swelling component swells.

12. The oral dosage form according to claim 11, wherein the first axis and the second axis become perpendicular to each other when the swelling component swells.

13. The drug dosage according to any one of claims 8 to 12, wherein at least a portion of the first component is configured to cooperate with the second component to create a point of rotation.

14. The drug dosage form according to claim 10, wherein the first axis and the second axis are aligned with each other, and when the swelling component swells, it is shifted away from the central axis.

15. The drug dosage form according to claim 14, further comprising a first guide track and a second guide track, wherein when the swellable component swells, the first component shifts toward the central axis together with the first guide track, and the second component shifts toward the central axis together with the second guide track.

16. The drug dosage form according to claim 14 or 15, further comprising a third component, a third guide track, a fourth component, and a fourth guide track, wherein when the swellable component swells, the third component shifts toward the central axis together with the third guide track, and the fourth component shifts toward the central axis together with the fourth guide track.

17. The drug dosage form according to any one of claims 1 to 16, wherein the first component comprises the first drug.

18. The drug dosage form according to any one of claims 8 to 17, wherein the second component comprises the second drug.

19. The drug dosage form according to any one of claims 15 to 18, wherein the third component comprises a third drug.

20. The drug dosage form according to any one of claims 15 to 19, wherein the fourth component comprises the fourth drug.

21. The drug dosage form according to any one of claims 1 to 20, wherein the swelling component comprises a core drug.

22. The drug dosage form according to any one of claims 1 to 20, wherein the swelling component does not contain a drug.

23. A drug dosage form according to any one of claims 17 to 21, wherein at least two of the first drug, the second drug, the third drug, the fourth drug, and the core drug are the same.

24. A drug dosage form according to any one of claims 17 to 21, wherein at least two of the first drug, the second drug, the third drug, the fourth drug, and the core drug are different from each other.

25. The drug dosage form according to any one of claims 17 to 21, wherein at least one of the first drug, the second drug, the third drug, the fourth drug, and the core drug is poorly water-soluble.

26. The drug dosage form according to any one of claims 17 to 21 and 23 to 25, wherein one of the first drug, the second drug, the third drug, the fourth drug, and the core drug is located in a compartment embedded in a base material.

27. The drug dosage form according to claim 26, wherein the first component, the second component, the third component, and / or the fourth component comprises a drug contained within a compartment.

28. The drug dosage form according to claim 22, wherein the compartment includes a plug.

29. The drug dosage form according to claim 27 or 28, wherein the first component, the second component, the third component, and / or the fourth component comprises two or more drug-filled compartments.

30. The drug dosage form according to any one of claims 1 to 29, wherein the drug dosage form is an oral drug dosage form.

31. A commercially available batch of a drug dosage form according to any one of claims 1 to 30, wherein the commercially available batch is The amount of drug in the aforementioned drug dosage form, The weight of the aforementioned drug dosage form, The maximum transverse dimension of the oral drug dosage form, A transverse dimension perpendicular to the maximum transverse dimension of the oral drug dosage form, The maximum transverse dimension of the oral drug dosage form after swelling of the swelling component, and A commercially available batch having a standard deviation of approximately 0.05 or less for each of the transverse dimensions perpendicular to the maximum transverse dimension of the oral drug dosage form after swelling of the swelling component.

32. The commercial batch according to claim 31, wherein the commercial batch comprises at least about 1,000 of the drug dosage forms.

33. The drug dosage form according to any one of claims 1 to 30, wherein the drug dosage form is manufactured by a 3D printing technique.

34. A method for three-dimensional (3D) printing of a drug dosage form according to any one of claims 1 to 30, wherein the method is (a) Discharging the first component or a part thereof, (b) A method comprising discharging the swellable component or a portion thereof.

35. The method according to claim 34, wherein the discharge is via molten extrusion deposition (MED).

36. The method according to claim 34 or 35, wherein the ejection of the first component or a part thereof, and the ejection of the swelling component or a part thereof are performed by different print heads.

37. A method for preparing drug dosage forms by three-dimensional (3D) printing, The drug dosage form comprises a first component, a second component, and a swelling component. The method described above is (a) Discharging the material of the first component, (b) Discharging the material of the second component, (c) A method comprising dispensing the material of the swelling component.

38. The method according to claim 37, wherein the discharge is via molten extrusion deposition (MED).

39. The method according to claim 37 or 38, wherein each material is ejected by a different print head.

40. The method according to any one of claims 34 to 39, wherein the drug dosage form is 3D printed using a layer-by-layer technique.

41. A method for delivering a drug into an organism, enabling the drug to be retained in the stomach of the organism for an extended period of time, wherein the method comprises orally administering a drug dosage form according to any one of claims 1 to 30 to the organism.

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