Risperidone dosage regimen using gastric residence system

Abstract

Dosage regimens for gastric retention systems comprising risperidone or a salt thereof are disclosed. The dosage regimen includes a regimen in which immediate release risperidone or a salt thereof is administered during a first period of time, immediate release risperidone or a salt thereof and a gastric resident system comprising risperidone or a salt thereof are administered during a second period of time, and a gastric resident system comprising risperidone or a salt thereof is administered during a third period of time. The dosage regimen also includes a regimen in which immediate release risperidone or a salt thereof is administered during the co-administration deadline, and a gastric resident system comprising risperidone or a salt thereof is administered during the co-administration deadline, and a gastric resident system comprising risperidone or a salt thereof is administered during a subsequent deadline.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the priority benefit of U.S. Provisional Patent Application 63 / 377,961, filed on September 30, 2022. The entire content of this application is incorporated herein by reference. Field of the Invention

[0003] The present invention relates to a risperidone dosing regimen using a gastric retention system for sustained intragastric release of an active agent. Background of the Invention

[0005] Gastric retention systems are delivery systems for retaining an active agent in the stomach for a period of days to weeks or even longer, during which the drug or other active agent can be eluted from the system for absorption in the gastrointestinal tract. Examples of such systems are described in U.S. Patent 10,182,985 and International Patent Applications WO 2015 / 191920, WO 2015 / 191925, WO 2017 / 070612, WO 2017 / 100367, WO 2017 / 205844, and WO 2018 / 227147. During the retention period, the system releases one or more active agents, such as one or more drugs.

[0006] Gastric retention systems for administering risperidone are disclosed in International Patent Applications WO 2021 / 092491 and WO 2022 / 159529.

[0007] The present invention describes a regimen for administering risperidone using a gastric retention system, including co - administration with an immediate - release dosage form of risperidone. Summary of the Invention

[0009] A risperidone dosage form is disclosed that includes a variety of features that provide more precise and consistent control of the desired residence time of a gastric retention system. These features include: filaments that wrap circumferentially around the gastric retention system and connect the arms of the gastric retention system; the use of timed joints and enteric joints that can more precisely retain and pass the gastric retention system; and arms coated with a polymer film that regulates the release rate.

[0010] Where appropriate and practical, the features of any of the above and herein described embodiments can be combined with any other embodiments cited above and herein. Brief Description of the Drawings

[0012] Figure 1A Showing the structure of the gastric retention system.

[0013] Figure 1B Showing a detailed view of the gastric retention structure.

[0014] Figure 2AShow the structure of the gastric retention system dosage form of risperidone.

[0015] Figure 2B Show another structure of the gastric retention system dosage form of risperidone.

[0016] Figure 3 Depict the pharmacokinetic profile of the risperidone formulation of the gastric retention system in Example 1 in a human subject (upper curve: 28 mg dosage form; lower curve: 14 mg dosage form).

[0017] Figure 4 Depict the pharmacokinetics of risperidone in a patient when transitioning from steady-state immediate-release (IR) risperidone to an extended-release (ER) risperidone gastric retention system. Plot the concentration of the active moiety (combined risperidone and 9-hydroxyrisperidone). The upper curve shows the concentration following administration of the 28 mg ER gastric retention system, while the lower curve shows the concentration following administration of the 14 mg ER gastric retention system. Bars representing the Cavg and Cmin of the corresponding matching IR group are overlaid on the curves.

[0018] Figure 5A Depict the pharmacokinetics of risperidone for a gastric retention system (ER) dose. Plot the mean concentration of the active moiety (combined risperidone and 9-hydroxyrisperidone), + / − standard deviation. The upper panel shows the 14 mg ER dose, while the lower panel shows the 28 mg ER dose. Bars representing the Cavg and Cmin on the last day of IR induction are overlaid on the figure.

[0019] Figure 5B Depict the concentration of the active moiety (combined risperidone and 9-hydroxyrisperidone) following daily IR administration of 2 mg (upper panel) and 4 mg (lower panel) of risperidone. Bars representing the Cavg and Cmin on the last day of IR induction are overlaid on the figure.

[0020] Figure 6A Depict the comparison of the Cavg, mean concentration of the active moiety (combined risperidone and 9-hydroxyrisperidone) on day -1 (i.e., immediately before transitioning from IR risperidone to the ER risperidone gastric retention system) and on day 15 for 2 mg IR vs. 14 mg ER and 4 mg IR vs. 28 mg ER.

[0021] Figure 6B Depict the comparison of the Ctau, i.e., trough concentration, of the active moiety (combined risperidone and 9-hydroxyrisperidone) on day -1 (i.e., immediately before transitioning from IR risperidone to the ER risperidone gastric retention system) and on day 15 for 2 mg IR vs. 14 mg ER and 4 mg IR vs. 28 mg ER.

[0022] Figure 7 Show the structure of the gastric retention system dosage form of risperidone.

[0023] Figure 8A The construction of the gastric-retention systemic dosage form of perrepone is shown. Figure 8B Another configuration of a gastric resident systemic dosage form of risperidone is shown. Figure 8C The configuration of the drug eluting arm within the gastric resident systemic dosage form of risperidone is shown. Figure 8D The active compound arm within a gastric resident systemic dosage form of risperidone is shown. Figure 8E An inactive composite arm within a gastric resident systemic dosage form of risperidone is shown.

[0024] Figure 9A The construction of the gastric-resident systemic dosage form of risperidone is shown. Figure 9B The configuration of the drug eluting arm (with active arm) within the gastric resident systemic dosage form of risperidone is shown. Figure 9C The configuration of the non-drug eluting arm (with an inactive arm) within a gastric resident systemic dosage form of risperidone is shown.

[0025] Figure 10A The construction of the gastric-resident systemic dosage form of risperidone is shown. Figure 10B The configuration of the drug eluting arm (with active arm) within the gastric resident systemic dosage form of risperidone is shown. Figure 10C The configuration of the non-drug eluting arm (with an inactive arm) within a gastric resident systemic dosage form of risperidone is shown.

[0026] Figure 11A The construction of the gastric-resident systemic dosage form of risperidone is shown. Figure 11B The configuration of the drug eluting arm (with active arm) within the gastric resident systemic dosage form of risperidone is shown. Figure 11C The configuration of the non-drug eluting arm (with an inactive arm) within a gastric resident systemic dosage form of risperidone is shown.

[0027] Figure 12 Shown are risperidone plasma levels for patients who received the initial immediate release (IR) dosage form for one week (only the last day of IR dosage form administration, day -1, is shown). The patient was then administered a gastric retention system containing risperidone on days 0, 7, and 14, i.e., weekly. The patient also received a supplemental IR dose of risperidone on days 0-6.

[0028] Figure 13A , Figure 13B and Figure 13C The plasma concentration of the active moiety in the patient is shown graphically. Figure 13A Plasma concentrations are shown for 21 subjects who received either the 15 mg risperidone gastric-retention system or the 45 mg risperidone gastric-retention system; plasma levels for the 45 mg group were divided by 3 in order to normalize their plasma levels to the 15 mg dose. Figure 13B Plasma levels are shown for the 15 mg dose group. Figure 13CShows the plasma levels of the 45 mg dose group. DETAILED DESCRIPTION OF THE INVENTION

[0030] DEFINITIONS

[0031] "Carrier polymer" is a polymer suitable for blending with an active agent, such as a drug, for a gastric retention system.

[0032] "Active agent" refers to any substance used for therapeutic, diagnostic, or nutritional purposes in a patient, individual, or subject. Active agents include, but are not limited to, drugs, nutrients, vitamins, and minerals.

[0033] "Dispersant" is defined as a substance that helps to minimize the particle size of the active agent and disperse the active agent particles in the carrier polymer matrix. That is, the dispersant helps to minimize or prevent the aggregation or flocculation of particles during system manufacture. Thus, the dispersant has anti-aggregation activity and anti-flocculation activity and helps to maintain the uniform distribution of the active agent particles in the carrier polymer matrix.

[0034] "Excipient" is any substance added to an active agent formulation other than the active agent itself. Excipients include, but are not limited to, binders, coating agents, diluents, disintegrants, emulsifiers, flavoring agents, glidants, lubricants, and preservatives. The specific category of dispersants belongs to the more general category of excipients.

[0035] "Elastomeric polymer" or "elastomer" is a polymer that is capable of deforming from its original shape for a period of time by an applied force and then substantially returning to its original shape once the applied force is removed.

[0036] "Approximately constant plasma level" refers to a plasma level that remains within a range of twice the average plasma level (i.e., 50% to 200% of the average plasma level) as measured during the time the gastric retention system remains in the stomach.

[0037] "Substantially constant plasma level" refers to a plasma level that remains within ±25% of the average plasma level as measured during the period that the gastric retention system remains in the stomach.

[0038] When used to describe a material or system, "biocompatible" means that when in contact with a living organism, such as a human, the material or system does not cause an adverse reaction, or only causes minimal, tolerable adverse reactions. In the case of a gastric retention system, biocompatibility is evaluated in the gastrointestinal environment.

[0039] "Patient", "individual", or "subject" refers to a mammal, preferably a human or a domestic animal such as a dog or a cat. In a most preferred embodiment, the patient, individual, or subject is a human.

[0040] As used herein, the "diameter" of a particle refers to the longest dimension of the particle.

[0041] "Treating" a disease or disorder with the systems and methods disclosed herein is defined as administering one or more of the systems disclosed herein, with or without an additional active agent, to a patient in need thereof to alleviate or eliminate the disease or disorder or one or more symptoms of the disease or disorder, or to retard the progression of the disease or disorder or one or more symptoms of the disease or disorder, or to reduce the severity of the disease or disorder or one or more symptoms of the disease or disorder. "Inhibiting" a disease or disorder with the systems and methods disclosed herein is defined as administering one or more of the systems disclosed herein, with or without an additional active agent, to a patient in need thereof to inhibit the clinical manifestation of the disease or disorder or the manifestation of the adverse symptoms of the disease or disorder. The difference between treating and inhibiting is that treatment occurs after the adverse symptoms of the disease or disorder have manifested in the patient, while inhibition occurs before the adverse symptoms of the disease or disorder have manifested in the patient. Inhibition can be partial, substantially complete, or complete. Because some diseases or disorders are genetic, genetic screening can be used to identify patients at risk of a disease or disorder. Then, the systems and methods disclosed herein can be used to treat asymptomatic patients at risk of developing the clinical symptoms of a disease or disorder in order to inhibit the appearance of any adverse symptoms.

[0042] The "therapeutic use" of the systems disclosed herein is defined as using one or more of the systems disclosed herein to treat a disease or disorder as defined above. A "therapeutically effective amount" of a therapeutic agent (e.g., a drug) is the amount of the active agent that, when administered to a patient, is sufficient to reduce or eliminate the disease or disorder or one or more symptoms of the disease or disorder, or to delay the progression of the disease or disorder or one or more symptoms of the disease or disorder, or to reduce the severity of the disease or disorder or one or more symptoms of the disease or disorder. A therapeutically effective amount can be administered to a patient as a single dose or can be divided and administered as multiple doses.

[0043] The "preventive use" of the systems disclosed herein is defined as using one or more of the systems disclosed herein to inhibit a disease or disorder as defined above. A "preventively effective amount" of an active agent is the amount of the active agent that, when administered to a patient, is sufficient to inhibit the clinical manifestation of the disease or disorder or the manifestation of the adverse symptoms of the disease or disorder. A preventively effective amount can be administered to a patient as a single dose or can be divided and administered as multiple doses.

[0044] The "flexural modulus" of a material is an inherent property of the material and is calculated as the ratio of stress to strain in the flexural deformation of the material measured by a three-point bending test. Although the joint is described herein as a component of a gastric retention system, the flexural modulus of the polymeric material can be measured separately. For example, the polymeric joint in a gastric retention system may be too short to measure the flexural modulus, but a longer sample of the same material can be used to accurately determine the flexural modulus. The longer sample used to measure the flexural modulus should have the same cross-sectional dimensions (shape and size) as the polymeric joint used in the gastric retention system. The flexural modulus is measured using a three-point bending test in accordance with ASTM standard three-point bending test (ASTM D790), measured with a 10 mm distance between the supports, and further modified to accommodate materials with non-rectangular cross-sections. The longest symmetry line of the cross-section of the polymeric joint should be positioned vertically, and the flexural modulus should be measured by applying a force downward. If the longest symmetry line of the cross-section of the polymeric joint is perpendicular to a single flat edge, the single flat edge should be positioned upward. If the cross-section of the polymeric joint is triangular, the vertex of the triangle should face downward. When a force is applied downward, the force and displacement are measured, and the slope in the linear region is obtained to calculate the flexural modulus.

[0045] The concentration of the active moiety of risperidone is the concentration of risperidone plus the concentration of 9-hydroxyrisperidone. The concentration of the active moiety of risperidone is typically measured in plasma.

[0046] As used herein, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise or is otherwise specified.

[0047] When the term "about" or the term "approximately" is used herein to indicate a numerical value, it should be understood to include the specified value and values reasonably close to the specified value. For example, the description "about 50 °C" or "approximately 50 °C" includes the disclosure of 50 °C itself and values close to 50 °C. Thus, the phrase "about X" or "approximately X" includes the description of the value X itself. If a range is indicated, such as "about 50 °C - 60 °C" or "about 50 °C - 60 °C", it should be understood to include the two values specified by the endpoints and, for each endpoint or both endpoints, values close to each endpoint or both endpoints; that is, "about 50 °C - 60 °C" (or "about 50 °C - 60 °C") is equivalent to reciting "50 °C - 60 °C" and "about 50 °C - about 60 °C" (or "about 50 °C - 60 °C").

[0048] Regarding the numerical ranges disclosed in this specification, the upper limit value of any disclosed component can be combined with the lower limit value of any disclosed component of that component to provide a range (provided that the upper limit value is greater than the lower limit value with which it is combined). Each of these combinations of the disclosed upper and lower limit values is specifically contemplated herein. For example, if the ranges for the amount of a particular component are given as 10% - 30%, 10% - 12%, and 15% - 20%, then the ranges of 10% - 20% and 15% - 30% are also contemplated, while the combination of a 15% lower limit value and a 12% upper limit value is not possible and thus not contemplated.

[0049] Unless otherwise specified, the percentages of the components in the composition are expressed as weight percentages or weight / weight percentages. It should be understood that the reference to the relative weight percentages in the composition presumes that the combined total weight percentage of all components in the composition totals 100. It should also be understood that the relative weight percentages of one or more components can be adjusted up or down such that the weight percentages of the components in the composition total 100, provided that the weight percentage of any particular component does not fall outside the limits of the range specified for that component.

[0050] Some of the embodiments described herein are recited with respect to their various elements as "comprising" or "including". In alternative embodiments, those elements can be recited with transitional phrases such as "consisting essentially of..." or "consisting of..." as applied to those elements. In further alternative embodiments, those elements can be recited with the transitional phrase "consisting of..." as applied to those elements. Thus, for example, if a composition or method is disclosed herein as comprising A and B, then the alternative embodiments of the composition or method "consisting essentially of A and B" and the alternative embodiments of the composition or method "consisting of A and B" are also considered to have been disclosed herein. Similarly, embodiments recited with respect to their various elements as "consisting essentially of..." or "consisting of..." can also be recited as "comprising" as applied to those elements. Finally, embodiments recited with respect to their various elements as "consisting essentially of..." can also be recited as "consisting of..." as applied to those elements, and embodiments recited with respect to their various elements as "consisting of..." can also be recited as "consisting essentially of..." as applied to those elements.

[0051] When a composition or system is described as "consisting essentially of the listed elements", the composition or system contains the explicitly listed elements and may contain other elements that do not substantially affect the disorder being treated (for a composition for treating a disorder) or the properties of the system (for a composition containing a system). However, except for the explicitly listed elements (for a composition for treating a system), the composition or system does not contain any other elements that do substantially affect the disorder being treated, or does not contain any other elements that do substantially affect the properties of the system (for a composition containing a system); or, if the composition or system does contain additional elements other than those listed that may substantially affect the disorder being treated or the properties of the system, the composition or system does not contain those additional elements in a sufficient concentration or amount to substantially affect the disorder being treated or the properties of the system. When a method is described as "consisting essentially of the listed steps", the method includes the listed steps and may include other steps that do not substantially affect the disorder treated by the method or the properties of the system produced by the method, but except for the explicitly listed steps, the method does not contain any other steps that substantially affect the disorder being treated or the system produced.

[0052] The present disclosure provides several embodiments. It is contemplated that, where possible, any feature from any embodiment can be combined with any feature from any other embodiment. In this way, a hybrid configuration of the disclosed features is within the scope of the present disclosure.

[0053] In addition to the embodiments and methods disclosed herein, additional embodiments of the gastric retention system and methods of making and using such systems are disclosed in International Patent Applications WO 2015 / 191920, WO 2015 / 191925, WO 2017 / 070612, WO 2017 / 100367, and PCT / US2017 / 034856 (WO 2017 / 205844), which are hereby incorporated by reference in their entirety.

[0054] The following abbreviations are used for polymers and other components:

[0055]

[0056]

[0057]

[0058] is a registered trademark of BASF Corporation for polyoxyalkylene ethers. In any formulation using a trade name herein, the trade name may be replaced with the generic name. For example, a formulation described as containing 50% Corbion PC17 and 50% Corbion PC04 is understood to describe a formulation containing 50% polycaprolactone with an intrinsic viscosity midpoint of 1.7 dl / g and 50% polycaprolactone with an intrinsic viscosity midpoint of 0.4 dl / g. Any component in any formulation using a trade name described herein may be replaced with an equivalent component from another manufacturer.

[0059] Unless otherwise specified, "copolymer of DL-lactide and glycolide" as used herein is understood to refer to an ester-terminated copolymer of DL-lactide and glycolide; and "poly(D,L-lactic-co-glycolide)" is understood to refer to an ester-terminated poly(D,L-lactic-co-glycolide).

[0060] As used herein, unless otherwise specified, "PCL" may refer to polycaprolactone having a variety of intrinsic viscosity midpoints, such as 1.0 - 2.1 dl / g, for example, polycaprolactone having an intrinsic viscosity midpoint of 1.7 dl / g or polycaprolactone having an intrinsic viscosity midpoint of 1.2 dl / g.

[0061] Gastric Retention System Description

[0062] Gastric retention systems can be prepared in different configurations. The "star-shaped" configuration of a gastric retention system is also referred to as the "star" (or "asterisk") configuration. An example of a star-shaped system 100 is schematically shown in Figure 1A . A plurality of arms (only one such arm 108 is labeled for clarity) are attached to a disc-shaped central elastomer 106. Figure 1A The arms depicted in Figure 1B are composed of segments 102 and 103, which are connected by a coupling polymer or a joint region 104 serving as a joint region (again, components are only labeled in one arm for clarity). This configuration allows the system to fold or compact at the central elastomer. Figure 1A shows the folded configuration 190 of the gastric retention system of Figure 1B (only two arms are exemplified for clarity in Figure 1B . The segments 192 and 193, joint region 194, elastomer 196, and arm 198 of Figure 1ASegments 102 and 103, junction region 104, elastomer 106, and arms 108. When folded, the overall length of the system is reduced by approximately two-fold, and the system can be conveniently placed in a container, such as a capsule or other suitable container, for oral administration. The gastric retention system is constrained by the capsule or other container in a compacted state (folded state). When the capsule reaches the stomach, the capsule dissolves, releasing the gastric retention system. After the capsule or other container releases the constraint, the gastric retention system unfolds into its uncompacted state, where it resides in the stomach for a desired residence period.

[0063] Although Figure 1A in which the junction region 104 is shown with a slightly larger diameter than segments 102 and 103, they can have the same diameter as the segments, such that the entire arm 102 - 104 - 103 has a smooth outer surface.

[0064] In some embodiments, the star-shaped system can have arms consisting of only one segment, which are attached to the central elastomer through a junction region. This is equivalent to Figure 1A , in which segment 103 is omitted. Then, the single-segment arm containing segment 102 is directly attached to the central elastomer 106 through junction 104. The junction can contain a coupling polymer or a disintegrating matrix.

[0065] The star-shaped system can be described as a gastric retention system for administration to a patient's stomach, comprising an elastomer assembly and a plurality of at least three carrier polymer - active agent assemblies, the carrier polymer - active agent assemblies comprising a carrier polymer and an active agent or a salt thereof, the carrier polymer - active agent assemblies being attached to the elastomer assembly, wherein each of the plurality of carrier polymer - active agent assemblies is an arm comprising a proximal end, a distal end, and an outer surface between the proximal end and the distal end; wherein the proximal end of each arm is attached to the elastomer assembly and projects radially from the elastomer assembly, the distal end of each arm is not attached to the elastomer assembly and is located at a greater radial distance from the elastomer assembly than the proximal end; wherein each arm independently comprises one or more segments, each segment comprising a proximal end, a distal end, and an outer surface between the proximal end and the distal end. In some embodiments, when there are two or more segments in an arm, each segment is attached to an adjacent segment through a junction region. In some embodiments, when there are two or more segments in an arm, one segment is directly attached to another segment without using a junction region. The junction region can be a coupling polymer or a disintegrating matrix. The arms can be attached to the central elastomer through a coupling polymer or a disintegrating matrix and can have an intervening portion of an interfacial polymer. For the plurality of at least three arms, or for the plurality of arms, the preferred number of arms is six, but three, four, five, seven, eight, nine, or ten arms can be used. The arms should be equidistantly spaced around the central elastomer; if there are N arms, there will be an angle of approximately 360 / N degrees between adjacent arms.

[0066] The coupling polymer of the gastric retention system serving as the joint region is designed to gradually decompose in a controlled manner during the retention of the system in the stomach. If the gastric retention system enters the small intestine prematurely in its intact form, the system is designed to decompose more rapidly to avoid intestinal obstruction. This is readily achieved by using an enteric polymer as the coupling polymer. Enteric polymers are relatively resistant to the acidic pH levels encountered in the stomach but dissolve at the higher pH levels found in the duodenum. Using an enteric coupling polymer as a safety element prevents the intact gastric retention system from undesirably entering the small intestine. In Figure 1A the system shown, the coupling polymer for at least the coupling piece 104 is made of such an enteric polymer.

[0067] In additional embodiments, a time-dependent coupling polymer or linker may be used. Such time-dependent coupling polymers or linkers degrade in a predictable time-dependent manner. In some embodiments, the degradation of the time-dependent coupling polymer or linker may be unaffected by pH changes in the gastrointestinal system.

[0068] In additional embodiments, different types of linkers may be used in the gastric retention system. That is, an enteric linker (or enteric coupling polymer) and a time-dependent linker (or time-dependent coupling polymer) may be used. In some embodiments, individual multi-segment arms of a star-shaped system may use an enteric linker at some joint regions between segments and a time-dependent linker at other joint regions between segments.

[0069] The width of the joint area is typically from about 100 microns to about 2 millimeters, such as about 200um to about 2000um, about 300um to about 2000um, about 400um to about 2000um, about 500um to about 2000um, about 600um to about 2000um, about 700um to about 2000um, about 800um to about 2000um, about 900um to about 2000um, about 1000um to about 2000um, about 1100um to about 2000um, about 1200um to about 2000um, about 1300um to about 2000um, about 1400um to about 2000um, about 1500um to about 2000um, about 1600um to about 2000um, about 1700um to about 2000um, about 1800um to about 2000um or about 1900um to about 2000um; or about 100um to about 1900um, about 100um to about 1800um, about 100um to about 1700um, about 100um to about 1600um, about 100um to about 1500um, about 100um to about 1400um, about 100 to about 1300um, about 100um to about 1200um, about 100um to about 1100um, about 100um to about 1000um, about 100um to about 900um, about 100um to about 800um, about 100um to about 700um, about 100um to about 600um, about 100um to about 500um, about 100um to about 400um, about 100um to about 300um or about 100um to about 200um. The width of the joint area can be about 100um, about 200um, about 300um, about 400um, about 500um, about 600um, about 700um, about 800um, about 900um, about 1000um, about 1100um, about 1200um, about 1300um, about 1400um, about 1500um, about 1600um, about 1700um, about 1800um, about 1900um or about 200oum, where each value can be plus or minus 50um (±50um).

[0070] The central elastomeric polymer of the star system is generally not an enteric polymer; however, if desired and practical, the central elastomeric polymer can also be made from such enteric polymers.

[0071] The central elastomer should have a specific hardness value and compression deformation. The hardness value is important as it determines the folding force of the dosage form and whether it will remain in the stomach; the preferred range is from about 60 to about 90 A. The compression deformation should be as low as possible to avoid permanent deformation of the gastric retention system when stored in a capsule in its compacted configuration. The preferred range is from about 10% to about 20%. Liquid silicone rubber is a useful material for the central elastomer. An example of a material meeting these requirements is the liquid silicone rubber of the QP1 series from Dow Corning. In any embodiment of the central elastomer, QP1-270 (70 A hardness value) liquid silicone rubber can be used. In some embodiments, the central elastomer can comprise liquid silicone rubber (Shin Etsu) with a hardness value of 50 A or 60 A.

[0072] The segments and arms of the gastric retention system can have a cross-section in the shape of a circle (in which case the segment is cylindrical), a polygon (e.g., a segment with a triangular cross-section, a rectangular cross-section, or a square cross-section), or a pie-shaped cross-section (in which case the segment is a cylindrical section). The ends of the segments with a polygon or pie-shaped cross-section and the cylindrical segments that will contact the gastric tissue can have their sharp edges rounded to provide rounded corners and edges for enhanced in vivo safety. That is, instead of having a sharp transition between intersecting edges or planes, an arc is used to transition from one edge or plane to another. Thus, a "triangular cross-section" includes a cross-section having an approximately triangular shape, such as a triangle with rounded corners. An arm with a triangular cross-section includes an arm with rounded edges, and the corners at the ends of the arm are rounded. The rounded corners and edges are also referred to as fillet corners, filleted corners, fillet edges, or filleted edges.

[0073] In some embodiments, when deployed (arms extended), the star-shaped system is from about 30 mm to about 60 mm. In some embodiments, when deployed, the star-shaped system is from about 41 mm to about 51 mm. When deployed. In some embodiments, when deployed, the star-shaped system is from about 45 mm to about 47 mm. In some embodiments, when deployed, the star-shaped system is about 46 mm.

[0074] Features for improved retention and active ingredient release of the risperidone gastric retention system

[0075] Using the features described herein, such as filaments that circumferentially surround the gastric retention system and connect the arms of the gastric retention system; using timed and enteric joints that allow for greater precision of retention and passage of the gastric retention system; and arms coated with a polymer film that modulates the release rate, the retention of the gastric retention system for a desired retention period and the release of the active agent from the gastric retention system can be improved, and they can be made more consistent.

[0076] Circumferential filament

[0077] In this circumferential filament disclosure, a gastric retention system comprising filaments for improving gastric retention and a method of preparing a gastric retention form with filaments are provided. In particular, a gastric retention system having the filaments described herein can contribute to improving the gastric retention of the gastric retention system. In particular, the filaments can contribute to providing a more consistent gastric retention time and / or a longer gastric retention time. Thus, the gastric retention system comprising filaments provided herein can provide a more predictable and / or controllable gastric retention time. A gastric retention system having a predictable and / or controllable gastric retention time can minimize the risk of premature deployment of the gastric retention system (e.g., in the esophagus) and causing an obstruction. A gastric retention system having a predictable and / or controllable gastric retention time can also minimize the likelihood that the gastric retention system passes through the stomach and unfolds later in the gastrointestinal tract (i.e., the intestine) or passes through the gastrointestinal tract without unfolding at all. In each of these possible scenarios, the therapeutic agent of the gastric retention dosage form is not delivered to the patient as intended.

[0078] However, it has been demonstrated that star-shaped gastric retention systems can be bent into configurations that allow premature passage through the patient's pylorus. A gastric retention system that passes through the pylorus prematurely cannot deliver the therapeutic agent of the gastric retention system to the patient. In addition, premature passage results in inconsistency, leading to unreliability, and impairs the efficacy of the gastric retention system.

[0079] The features of the circumferential filament are described in International Patent Application PCT / US2020 / 059541 (WO 2021 / 092491), the entire content of which is incorporated herein by reference.

[0080] In some embodiments, the filaments are non-disintegrable filaments. In some embodiments, the filaments comprise a thermoplastic polyurethane, such as Pellethane 80A. In some embodiments, the filaments comprise methylene bis(4-phenyl isocyanate), poly(tetramethylene oxide), and 1,4-butanediol. In some embodiments, the filaments are disintegrating filaments. In some embodiments, the filaments comprise poly(lactic-co-glycolic acid). In some embodiments, the filaments comprise polyglycolic acid. In some embodiments, the thickness of the filaments is any one of about 0.05 mm, 0.1 mm, 0.15 mm, 0.20 mm, 0.25 mm, 0.30 mm, 0.35 mm, 0.40 mm, 0.45 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.0 mm or any thickness therebetween. In some embodiments, the thickness of the filaments is about 0.20 mm. In some embodiments, the thickness of the filaments is about 0.30 mm.

[0081] In some embodiments, the length of each segment of filament connecting two adjacent arms can be from about 20 - about 25 mm in length, such as from about 21 - about 24 mm in length, such as about 22.8 mm. In some embodiments, the total length of the circumferential filaments can be from about 95 mm - about 120 mm, or the total length can be from about 100 mm - about 150 mm, such as the total length is about 105 mm.

[0082] Timing connectors (timing disintegrating matrices) and enteric connectors (enteric disintegrating matrices)

[0083] Polymer connectors

[0084] The active agent-containing structural member is attached to the second structural member (such as a central member, which can be an elastic central member) by one or more connectors. The polymer connector can be directly interfaced with the active agent-containing structural member, or can be interfaced with the active agent-containing structural member through a coupling member. Similarly, the polymer connector can be directly interfaced with the second structural member, or can be interfaced through a coupling member. In embodiments where the active agent-containing structural member is connected to the second structural member by two or more polymer connectors, the polymer connectors can be directly interfaced with each other, or can be interfaced through a coupling member. One or both of an enteric connector and a time-dependent connector can be used, or the polymer connector can serve as both an enteric connector and a time-dependent connector.

[0085] The width of the polymer joint is generally about 100 microns to about 3 millimeters, such as about 200um to about 3000um, about 300um to about 3000um, about 400um to about 3000um, about 500um to about 3000um, about 600um to about 3000um, about 700um to about 3000um, about 800um to about 3000um, about 900um to about 3000um, about 1000um to about 3000um, about 1100um to about 3000um, about 1200um to about 3000um, about 1300um to about 3000um, about 1400um to about 3000um, about 1500um to about 3000um, about 1600um to about 3000um, about 1700um to about 3000um, about 1800um to about 3000um, about 1900um to about 3000um, about 2000um to about 3000um, about 2100um to about 3000um, about 2200um to about 3000um, about 2300um to about 3000um, about 2400um to about 3000um, about 2500um to about 3000um, about 2600um to about 3000um, about 2700um to about 3000um, about 2800um to about 3000um, or about 2900um to about 3000um; or about 100um to about 200um, about 200um to about 300um, about 300um to about 400um, about 400um to about 500um, about 500um to about 600um, about 600um to about 700um, about 700um to about 800um, about 800um to about 900um, about 900um to about 1000um, about 1000um to about 1100um, about 1100um to about 1200um, about 1200um to about 1300um, about 1300um to about 1400um, about 1400um to about 1500um, about 1500um to about 1600um, about 1600um to about 1700um, about 1700um to about 1800um, about 1800um to about 1900um, about 1900um to about 2000um, about 2000um to about 2100um, about 2100um to about 2200um, about 2200um to about 2300um, about 2300um to about 2400um, about 2400um to about 2500um, about 2500um to about 2600um, about 2600um to about 2700um, about 2700um to about 2800um, about 2800um to about 2900um, about 2900um to about 3000um.The width of the polymeric joint can be about 100 um, about 200 um, about 300 um, about 400 um, about 500 um, about 600 um, about 700 um, about 800 um, about 900 um, about 1000 um, about 1100 um, about 1200 um, about 1300 um, about 1400 um, about 1500 um, about 1600 um, about 1700 um, about 1800 um, about 1900 um, about 2000 um, about 2100 um, about 2200 um, about 2300 um, about 2400 um, about 2500 um, about 2600 um, about 2700 um, about 2800 um, about 2900 um, about 3000 um, where each value can be plus or minus 50 um (±50 um).

[0086] The cross-section of the polymeric joint can be circular (i.e., round), oval, triangular, square, rectangular, pentagonal, hexagonal, or any other polymeric shape. In some embodiments, the cross-section of the polymeric joint has the same shape as the cross-section of the active agent-containing structural member attached to the polymeric joint. In some embodiments, the cross-section of the polymeric joint has a larger area than the cross-section of the active agent-containing structural member, a smaller area than the cross-section of the active agent-containing structural member, or an area approximately the same as the cross-section of the attached active agent-containing structural member.

[0087] Time-dependent disintegration matrix (time-dependent joint)

[0088] Under aqueous conditions, such as when the gastric retention system unfolds in an individual's stomach, the time-dependent joint degrades in a predictable time-dependent manner. The time-dependent polymeric joint controls the residence time of the gastric retention system in the stomach. The time-dependent polymeric joint is designed to gradually degrade, dissolve, mechanically weaken, or break over time. After the desired residence period, the time-dependent polymeric joint has degraded, dissolved, dissociated, or mechanically weakened, or has broken to the extent that the gastric retention system can pass through the pyloric valve, leave the gastric environment, and enter the small intestine, and ultimately be eliminated from the body.

[0089] The time-dependent polymeric joint preferably comprises a pH-independent degradable polymer that degrades in an aqueous condition in a pH-independent or approximately pH-independent manner. Exemplary pH-independent degradable polymers include PLGA, PLA, PCL, polydioxanone, cellulose, or blends or copolymers thereof.

[0090] The time-dependent polymeric joint can include poly(lactic-co-glycolic acid) (PLGA).

[0091] In some embodiments, the PLGA of the time-dependent polymer linker comprises an ester-capped copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (e.g., about 0.4 dl / g) (e.g., PLGA sold under the trade name PDLG 5004, available from Corbion). In some embodiments, the PLGA of the time-dependent polymer linker comprises an acid-capped copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (e.g., about 0.4 dl / g) (e.g., PLGA sold under the trade name PDLG 5004A, available from Corbion). In some embodiments, the PLGA of the time-dependent polymer linker comprises a mixture of: (a) an ester-capped poly(D,L-lactide-co-glycolide) in which the ratio of lactide monomer to glycolide monomer is about 50:50 (e.g., PLGA sold under the trade name PDLG 5004, available from Corbion), and (b) an acid-capped poly(D,L-lactide-co-glycolide) in which the ratio of lactide monomer to glycolide monomer is about 50:50 (e.g., PLGA sold under the trade name PDLG 5004A, available from Corbio).

[0092] One or more additional linker polymers included in the polymer linker are preferably homogeneously mixed with the PLGA. In some embodiments, one or more additional linker polymers are miscible with the PLGA. One or more additional linker polymers can be non-degradable polymers (i.e., non-degradable or not degradable in the stomach or intestine or in an aqueous solution at pH 1.6 (representing the stomach environment) or pH 6.5 (representing the intestinal environment)), and optionally present in the time-dependent polymer linker in an amount such that the time-dependent polymer linker does not break during the gastric residence period.

[0093] If at least one polymer is common to the adjacent member and the time-dependent polymer linker, the connection of the polymer linker to the directly adjacent member can be improved. In some embodiments, at least one common polymer is polycaprolactone (PCL).

[0094] In some embodiments, one or more additional linker polymers comprise PCL. The time-dependent polymer linker can be directly attached or bonded to another component of the gastric retention system (e.g., a structural component comprising a drug and a carrier polymer, a coupling component, an enteric polymer linker, or a central structural component), which can also comprise PCL, which can be the same PCL as in the time-dependent polymer linker or a different PCL from the PCL in the polymer linker, and which can have the same concentration or a different concentration. The different PCLs in the time-dependent polymer linker and the other component directly attached or bonded to the time-dependent linker can differ in terms of, for example, the weight average molecular weight of the PCL, the intrinsic viscosity of the PCL, or the proportion of the PCL (e.g., when using a blend of two or more PCL polymers). In some embodiments, the time-dependent disintegrating matrix comprises from about 40 wt% to about 50 wt% of PCL. In some embodiments, the time-dependent disintegrating matrix comprises from about 43 wt% to about 47 wt% of PCL. In some embodiments, the time-dependent disintegrating matrix comprises about 45 wt% of PCL. In some embodiments, the time-dependent disintegrating matrix comprises about 44.95 wt% of PCL. In some embodiments, the time-dependent disintegrating matrix comprises from about 45 wt% to about 55 wt% of PCL. In some embodiments, the time-dependent disintegrating matrix comprises from about 48 wt% to about 52 wt% of PCL. In some embodiments, the time-dependent disintegrating matrix comprises about 50 wt% of PCL. In some embodiments, the time-dependent disintegrating matrix comprises about 49.95 wt% of PCL. In some embodiments, the PCL has a viscosity midpoint of from about 1.5 dl / g to about 2.1 dl / g, such as about 1.7 dl / g, e.g., Corbion PC17. In some embodiments, the PCL has a viscosity midpoint of from about 1.0 dl / g to about 1.4 dl / g, such as about 1.2 dl / g, e.g., Corbion PC12.

[0095] The time-dependent polymeric joint may also comprise one or more plasticizers, such as polyethylene glycol. The term "polyethylene glycol" may be used interchangeably herein with the terms "polyoxyethylene" and "PEO". In some embodiments, the molecular weight of the polyethylene glycol is from about 90K to about 110K, such as 100k (also referred to as 100K or 100 kDa). In some embodiments, the time-dependent disintegrating matrix comprises polyethylene glycol having a molecular weight of about 100k (polyethylene glycol 100k). In some embodiments, the time-dependent disintegrating matrix comprises from about 0.5 wt% to about 5 wt% of polyethylene glycol 100k. In some embodiments, the time-dependent disintegrating matrix comprises from about 1 wt% to about 3 wt% of polyethylene glycol 100k. In some embodiments, the time-dependent disintegrating matrix comprises about 2 wt% of polyethylene glycol 100k. In some embodiments, the time-dependent disintegrating matrix comprises from about 1.5 wt% to about 3.5 wt% of polyethylene glycol 100k. In some embodiments, the time-dependent disintegrating matrix comprises about 2.5 wt% of polyethylene glycol 100k. In some embodiments, the time-dependent disintegrating matrix includes a color-absorbing dye (also referred to as a colorant or pigment). A color-absorbing dye may be included to enhance the bonding or attachment of the polymeric joint to other components of the gastric retention system. The color-absorbing dye may absorb heat during laser welding, infrared welding, or other heat-induced attachment, which increases the tensile strength of the resulting connection. Exemplary color-absorbing dyes include iron oxide and carbon black. The time-dependent disintegrating matrix may include up to about 5%, such as up to about 4%, up to about 3%, up to about 2%, up to about 1%, up to about 0.5%, up to about 0.3%, up to about 0.2%, up to about 0.1%, or up to about 0.05% by weight of the color-absorbing dye. In some embodiments, the time-dependent disintegrating matrix comprises from about 0.005 wt% to about 0.2 wt% of the color-absorbing dye. In some embodiments, the time-dependent disintegrating matrix comprises from about 0.01 wt% to about 0.1 wt% of the color-absorbing dye. In some embodiments, the time-dependent disintegrating matrix comprises about 0.05 wt% of the color-absorbing dye. In some embodiments, the color-absorbing dye is E172.

[0096] In an example of the time-dependent disintegration matrix, the time-dependent disintegration matrix comprises about 40 wt% - about 50 wt% of PCL, about 30 wt% - about 40 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 10 wt% - about 25 wt% of a copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color-absorbing dye E172. In an example of the time-dependent disintegration matrix, the time-dependent disintegration matrix comprises about 40 wt% - about 50 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.5 dl / g - about 1.9 dl / g), about 30 wt% - about 40 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 10 wt% - about 25 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color-absorbing dye E172. In an example of the time-dependent disintegration matrix, the time-dependent disintegration matrix comprises about 40 wt% - about 50 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g), about 30 wt% - about 40 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 10 wt% - about 25 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color-absorbing dye E172. In an example of the time-dependent disintegration matrix, the time-dependent disintegration matrix comprises about 45 wt% - about 55 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g), about 27 wt% - about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 12 wt% - about 22 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color-absorbing dye E172.In one example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 45 wt% - about 55 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g), about 33 wt% - about 43 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 5 wt% - about 15 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color-absorbing dye E172. In one example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 45 wt% - about 55 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g), about 30 wt% - about 40 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 8 wt% - about 18 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color-absorbing dye E172. In one example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 45 wt% - about 55 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g), about 27 wt% - about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 12 wt% - about 22 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color-absorbing dye E172.

[0097] In another example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises from about 43 wt% to about 47 wt% PCL, from about 33 wt% to about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, from about 15 wt% to about 20 wt% of a copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, from about 1 wt% to about 3 wt% polyethylene glycol 100k, and from about 0.01 wt% to about 0.1 wt% of a color-absorbing dye E172. In one example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises from about 43 wt% to about 47 wt% PCL (e.g., PCL having a viscosity midpoint of about 1.5 dl / g to about 1.9 dl / g), from about 33 wt% to about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, from about 15 wt% to about 20 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, from about 1 wt% to about 3 wt% polyethylene glycol 100k, and from about 0.01 wt% to about 0.1 wt% of a color-absorbing dye E172. In one example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises from about 43 wt% to about 47 wt% PCL (e.g., PCL having a viscosity midpoint of about 1.0 dl / g to about 1.4 dl / g), from about 33 wt% to about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, from about 15 wt% to about 20 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, from about 1 wt% to about 3 wt% polyethylene glycol 100k, and from about 0.01 wt% to about 0.1 wt% of a color-absorbing dye E172. In one example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises from about 48 wt% to about 52 wt% PCL (e.g., PCL having a viscosity midpoint of about 1.0 dl / g to about 1.4 dl / g), from about 30 wt% to about 34 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, from about 14 wt% to about 18 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, from about 1 wt% to about 3 wt% polyethylene glycol 100k, and from about 0.01 wt% to about 0.1 wt% of a color-absorbing dye E172.In one example of the time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 48 wt% - about 52 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g), about 36 wt% - about 40 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 8 wt% - about 12 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 1 wt% - about 3 wt% of polyethylene glycol 100k, and about 0.01 wt% - about 0.1 wt% of a color-absorbing dye E172. In one example of the time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 48 wt% - about 52 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g), about 33 wt% - about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 11 wt% - about 15 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 1 wt% - about 3 wt% of polyethylene glycol 100k, and about 0.01 wt% - about 0.1 wt% of a color-absorbing dye E172. In one example of the time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 48 wt% - about 52 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g), about 30 wt% - about 34 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 14 wt% - about 18 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 1.5 wt% - about 3.5 wt% of polyethylene glycol 100k, and about 0.01 wt% - about 0.1 wt% of a color-absorbing dye E172.

[0098] In another example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 44.95 wt% PCL, about 35 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 18 wt% of a copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% polyethylene glycol 100k and about 0.05 wt% of a color-absorbing dye E172. In one example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 44.95 wt% PCL (e.g., PCL having a viscosity midpoint of about 1.7 dl / g, e.g., Corbion PC 17), about 35 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 18 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% polyethylene glycol 100k and about 0.05 wt% of a color-absorbing dye E172. In one example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 44.95 wt% PCL (e.g., PCL having a viscosity midpoint of about 1.2 dl / g, e.g., Corbion PC 12), about 35 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 18 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% polyethylene glycol 100k and about 0.05 wt% of a color-absorbing dye E172. In one example of a time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 49.95 wt% PCL (e.g., PCL having a viscosity midpoint of about 1.2 dl / g, e.g., Corbion PC 12), about 32 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 16 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% polyethylene glycol 100k and about 0.05 wt% of a color-absorbing dye E172.In one example of the time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 49.95 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.2 dl / g, such as Corbion PC 12), about 38 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 10 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% of polyethylene glycol 100k, and about 0.05 wt% of a color-absorbing dye E172. In one example of the time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 49.95 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.2 dl / g, such as Corbion PC 12), about 35 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 13 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% of polyethylene glycol 100k, and about 0.05 wt% of a color-absorbing dye E172. In one example of the time-dependent disintegrating matrix, the time-dependent disintegrating matrix comprises about 49.95 wt% of PCL (e.g., PCL having a viscosity midpoint of about 1.2 dl / g, such as C0rbionPC 12), about 31.75 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 15.75 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2.5 wt% of polyethylene glycol 100k, and about 0.05 wt% of a color-absorbing dye E172.

[0099] In some embodiments, the dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 44.95 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 35.0 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), such as PDLG 5004A. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 18.0 wt% of a copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), such as PDLG 5004. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 2.0 wt% of polyethylene glycol, such as polyethylene glycol having an average molecular weight of 100,000, such as PEO 100K . In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 0.05 wt% of iron oxide, such as E172. In some embodiments, the dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 44.95 wt% of Corbion PC17, about 35.0 wt% of PDLG 5004A, about 18.0 wt% of PDLG 5004, about 2.0 wt% of PEO 100K and about 0.05 wt% of E172.

[0100] In some embodiments, a dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 44.95 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g, such as 1.2 dl / g, for example Corbion PC12. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 35.0 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), for example PDLG 5004A. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 18.0 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), for example PDLG 5004. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 2.0 wt% of polyethylene glycol, such as polyethylene glycol having an average molecular weight of 100,000, for example PEO 100K . In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 0.05 wt% of iron oxide, such as E172. In some embodiments, a dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 44.95 wt% of Corbion PC12, about 35.0 wt% of PDLG 5004A, about 18.0 wt% of PDLG 5004, about 2.0 wt% of PEO 100K and about 0.05 wt% of E172.

[0101] In some embodiments, the dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 49.95 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g, such as 1.2 dl / g, for example Corbion PC12. In some embodiments, the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 32.0 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), for example PDLG 5004A. In some embodiments, the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 16.0 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), for example PDLG 5004. In some embodiments, the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 2.0 wt% of polyethylene glycol, such as polyethylene glycol having an average molecular weight of 100,000, for example PEO 100K . In some embodiments, the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 0.05 wt% of iron oxide, such as E172. In some embodiments, the dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 49.95 wt% of Corbion PC12, about 32.0 wt% of PDLG 5004A, about 16.0 wt% of PDLG 5004, about 2.0 wt% of PEO 100K and about 0.05 wt% of E172.

[0102] In some embodiments, a dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 49.95 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g, such as 1.2 dl / g, e.g., Corbion PC12. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 38.0 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (e.g., about 0.4 dl / g), such as PDLG 5004A. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 10.0 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (e.g., about 0.4 dl / g), such as PDLG 5004. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 2.0 wt% of polyethylene glycol, such as polyethylene glycol having an average molecular weight of 100,000, e.g., PEO 100K . In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 0.05 wt% of iron oxide, such as E172. In some embodiments, a dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 49.95 wt% of Corbion PC12, about 38.0 wt% of PDLG 5004A, about 10.0 wt% of PDLG 5004, about 2.0 wt% of PEO 100K and about 0.05 wt% of E172.

[0103] In some embodiments, a dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 49.95 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g, such as 1.2 dl / g, for example Corbion PC12. In some embodiments, the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 35.0 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), for example PDLG 5004A. In some embodiments, the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 13.0 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), for example PDLG 5004. In some embodiments, the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 2.0 wt% of polyethylene glycol, such as polyethylene glycol having an average molecular weight of 100,000, for example PEO 100K . In some embodiments, the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 0.05 wt% of iron oxide, such as E172. In some embodiments, a dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegrating matrix, and the time-dependent disintegrating matrix comprises about 49.95 wt% of Corbion PC12, about 35.0 wt% of PDLG5004A, about 13.0 wt% of PDLG 5004, about 2.0 wt% of PEO 100K and about 0.05 wt% of E172.

[0104] In some embodiments, the dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 49.95 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.0 dl / g - about 1.4 dl / g, such as 1.2 dl / g, for example Corbion PC12. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 31.75 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), for example PDLG 5004A. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 15.75 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), for example PDLG 5004. In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 2.5 wt% of polyethylene glycol, such as polyethylene glycol having an average molecular weight of 100,000, for example PEO 100K . In some embodiments, the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 0.05 wt% of iron oxide, such as E172. In some embodiments, the dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 49.95 wt% of Corbion PC12, about 31.75 wt% of PDLG 5004A, about 15.75 wt% of PDLG 5004, about 2.5 wt% of PEO 100K and about 0.05 wt% of E172.

[0105] Exemplary amounts of the components for the time-dependent disintegration matrix are provided in the table below. The amounts are given in approximate weight percentages and it is understood that when ranges are provided, the amounts are selected such that the total is 100%.

[0106]

[0107]

[0108] Exemplary amounts of the components for the time-dependent disintegration matrix are provided in the table below. The amounts are given in approximate weight percentages and it is understood that when ranges are provided, the amounts are selected such that the total is 100%.

[0109] Time-dependent disintegration matrix (T-DM1) Formulation 1 Formulation 2 Formulation 3 PCL (midpoint viscosity 1.7 dl / g) 40-50 43-47 44.95 PDLG5004A 30-40 33-37 35 PDLG5004 10-25 15-20 18 PEO (100k) 0.5-5 1-3 2 Colorant (optional) 0.005-0.2 0.01-0.1 0.05 (e.g., E172)

[0110] Exemplary amounts of components for a time-dependent disintegration matrix are provided in the table below. The amounts are given as approximate weight percentages and it is understood that when ranges are provided, the amounts are selected so as to total 100%.

[0111] Time-dependent disintegration matrix (T-DM2) Formulation 1 Formulation 2 Formulation 3 PCL (midpoint viscosity 1.2 dl / g) 40-50 43-47 44.95 PDLG5004A 30-40 33-37 35 PDLG5004 10-25 15-20 18 PEO (100k) 0.5-5 1-3 2 Colorant (optional) 0.005-0.2 0.01-0.1 0.05 (e.g., E172)

[0112] Exemplary amounts of components for a time-dependent disintegration matrix are provided in the table below. The amounts are given as approximate weight percentages and it is understood that when ranges are provided, the amounts are selected so as to total 100%.

[0113]

[0114]

[0115] Exemplary amounts of components for a time-dependent disintegration matrix are provided in the table below. The amounts are given as approximate weight percentages and it is understood that when ranges are provided, the amounts are selected so as to total 100%.

[0116] Time-dependent disintegration matrix (T-DM4) Formulation 1 Formulation 2 Formulation 3 PCL (midpoint viscosity 1.2 dl / g) 45-55 48-52 49.95 PDLG5004A 33-43 36-40 38 PDLG5004 5-15 8-12 10 PEO (100k) 0.5-5 1-3 2 Colorant (optional) 0.005-0.2 0.01-0.1 0.05 (e.g., E172)

[0117] Exemplary amounts of components for a time-dependent disintegration matrix are provided in the table below. The amounts are given as approximate weight percentages and it is understood that when ranges are provided, the amounts are selected so as to total 100%.

[0118] Time-dependent disintegration matrix (T-DM5) Formulation 1 Formulation 2 Formulation 3 PCL (midpoint viscosity 1.2 dl / g) 45-55 48-52 49.95 PDLG5004A 30-40 33-37 35 PDLG5004 8-18 11-15 13 PEO (100k) 0.5-5 1-3 2 Colorant (optional) 0.005-0.2 0.01-0.1 0.05 (e.g., E172)

[0119] Exemplary amounts of components for a time-dependent disintegration matrix are provided in the table below. The amounts are given as approximate weight percentages and it is understood that when ranges are provided, the amounts are selected so as to total 100%.

[0120] Time-dependent disintegration matrix (T-DM6) Formulation 1 Formulation 2 Formulation 3 PCL (midpoint viscosity 1.2 dl / g) 45-55 48-52 49.95 PDLG5004A 27-37 30-34 31.75 PDLG5004 10-22 14-18 15.75 PEO (100k) 0.5-5 1.5-3.5 2.5 Colorant (optional) 0.005-0.2 0.01-0.1 0.05 (e.g., E172)

[0121] Gastric retention time

[0122] The gastric retention time of the system is controlled by the degradation or weakening or breaking rate of the time-dependent polymer linker in the gastric retention system. Faster degradation or weakening or breaking of the time-dependent polymer linker results in faster passage of the system from the stomach. The retention time of the gastric retention system is defined as the time between administration of the system to the stomach and the system leaving the stomach. In one embodiment, the gastric retention system has a retention time of about 24 hours or up to about 24 hours. In one embodiment, the gastric retention system has a retention time of about 48 hours or up to about 48 hours. In one embodiment, the gastric retention system has a retention time of about 72 hours or up to about 72 hours. In one embodiment, the gastric retention system has a retention time of about 96 hours or up to about 96 hours. In one embodiment, the gastric retention system has a retention time of about 5 days or up to about 5 days. In one embodiment, the gastric retention system has a retention time of about 6 days or up to about 6 days. In one embodiment, the gastric retention system has a retention time of about 7 days (about one week) or up to about 7 days (about one week). In one embodiment, the gastric retention system has a retention time of about 10 days or up to about 10 days. In one embodiment, the gastric retention system has a retention time of about 14 days (about two weeks) or up to about 14 days (about two weeks).

[0123] In one embodiment, the gastric retention system has a retention time of about 24 hours to about 7 days. In one embodiment, the gastric retention system has a retention time of about 48 hours to about 7 days. In one embodiment, the gastric retention system has a retention time of about 72 hours to about 7 days. In one embodiment, the gastric retention system has a retention time of about 96 hours to about 7 days. In one embodiment, the gastric retention system has a retention time of about 5 days to about 7 days. In one embodiment, the gastric retention system has a retention time of about 6 days to about 7 days.

[0124] In one embodiment, the gastric retention system has a retention time of about 24 hours to about 10 days. In one embodiment, the gastric retention system has a retention time of about 48 hours to about 10 days. In one embodiment, the gastric retention system has a retention time of about 72 hours to about 10 days. In one embodiment, the gastric retention system has a retention time of about 96 hours to about 10 days. In one embodiment, the gastric retention system has a retention time of about 5 days to about 10 days. In one embodiment, the gastric retention system has a retention time of about 6 days to about 10 days. In one embodiment, the gastric retention system has a retention time of about 7 days to about 10 days.

[0125] In one embodiment, the gastric retention system has a retention time of about 24 hours to about 14 days. In one embodiment, the gastric retention system has a retention time of about 48 hours to about 14 days. In one embodiment, the gastric retention system has a retention time of about 72 hours to about 14 days. In one embodiment, the gastric retention system has a retention time of about 96 hours to about 14 days. In one embodiment, the gastric retention system has a retention time of about 5 days to about 14 days. In one embodiment, the gastric retention system has a retention time of about 6 days to about 14 days. In one embodiment, the gastric retention system has a retention time of about 7 days to about 14 days. In one embodiment, the gastric retention system has a retention time of about 10 days to about 14 days.

[0126] The gastric retention system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least a portion of the retention time or during the residence of the system in the stomach. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 25% of the retention time. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 50% of the retention time. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 60% of the retention time. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 70% of the retention time. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 75% of the retention time. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 80% of the retention time. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 85% of the retention time. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 90% of the retention time. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 95% of the retention time. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 98% of the retention time. In one embodiment, the system releases a therapeutically effective amount of the active agent (or a salt thereof) during at least about 99% of the retention time.

[0127] Enteric disintegrating matrix (enteric junction)

[0128] The pH-dependent disintegration matrix provides a safety mechanism for the gastric retention system. If the system leaves the stomach prematurely, i.e., with all time-dependent disintegration matrices intact, the pH-dependent disintegration matrix will degrade, dissolve, dissociate, or mechanically weaken in the high-pH environment of the small intestine, allowing the gastric retention system to pass easily through the small intestine. Additionally, after the gastric retention system has passed, once the time-dependent disintegration matrix degrades, dissolves, dissociates, or mechanically weakens in the gastric environment, exposure of the pH-dependent disintegration matrix to the high pH of the small intestine provides further weakening and / or decomposition of the system to prepare for passage through the small intestine.

[0129] If the gastric retention system enters the small intestine prematurely in its intact form, the system can be designed to break down more quickly to avoid intestinal obstruction. This is easily achieved by using an enteric polymer linker that includes an enteric polymer in addition to another linker polymer (such as a carrier polymer) that weakens or degrades within the intestinal environment. The enteric polymer is relatively resistant to the acidic pH levels encountered in the stomach but dissolves rapidly at the higher pH levels found in the duodenum. Using the enteric polymer linker as a safety element prevents the intact gastric retention system from passing undesirably into the small intestine. The use of the enteric polymer linker also provides a means of removing the gastric retention system before its designed residence time; if removal of the system is required, the patient can drink a weakly alkaline solution such as sodium bicarbonate solution or take an antacid preparation such as magnesium hydroxide hydrate (milk of magnesia) or calcium carbonate, which will raise the pH level in the stomach and cause rapid degradation of the enteric polymer linker.

[0130] Weakening or degradation of the enteric polymer linker can be measured by reference to the loss of flexural modulus or breakage of the polymer linker under given conditions (such as enteric conditions or gastric conditions). The enteric linker weakens, degrades, or breaks relatively rapidly in the intestinal environment while retaining most of its flexural modulus in the gastric environment. Gastric conditions can be simulated using an aqueous solution with a pH of 1.6 and at 37 °C (such as fasting state simulated gastric fluid (FaSSGF)), and intestinal conditions can be simulated using an aqueous solution with a pH of 6.5 and at 37 °C (such as fasting state simulated intestinal fluid (FaSSIF)).

[0131] In some embodiments, the enteric disintegration matrix comprises hypromellose acetate succinate (HPMCAS). For example, in some embodiments, the enteric disintegration matrix comprises from about 60 wt% to about 70 wt% of HPMCAS. In some embodiments, the enteric disintegration matrix comprises from about 62 wt% to about 66 wt% of HPMCAS. In some embodiments, the enteric disintegration matrix comprises about 63.95 wt% of HPMCAS.

[0132] The enteric polymer is combined with one or more additional polymers in the enteric linker (such as one or more carrier polymers), preferably in a homogeneous mixture. For example, the enteric polymer and the additional linker polymer can be uniformly blended together before mixture extrusion, and the extruded material is cut into the desired size of the polymer linker. In some embodiments, one or more additional linker polymers are miscible with the enteric polymer. One or more additional linker polymers can be non-degradable polymers (i.e., non-degradable or in a gastric or intestinal environment, or an aqueous solution at pH 1.6 (representing the gastric environment) or pH 6.5 (representing the intestinal environment)).

[0133] If at least one polymer is common to the adjacent member and the enteric polymer linker, the connection between the polymer linker and the directly adjacent member can be improved. That is, one of the one or more additional linker polymers in the enteric linker can be the same (or the same polymer type) as at least one polymer in the directly adjacent component (or optionally two directly adjacent components) of the gastric retention system. For example, if the enteric polymer linker is directly connected to a structural member containing a carrier polymer, in some embodiments, one or more additional linker polymers also include the same or different concentrations of the carrier polymer (in addition to PLGA in the time-dependent polymer linker). Exemplary carrier polymers include but are not limited to polylactic acid (PLA), polycaprolactone (PCL), and thermoplastic polyurethane (TPU) as described herein.

[0134] In some embodiments, one or more additional linker polymers in the enteric linker contain PCL. The enteric polymer linker can be directly connected or bonded to another member of the gastric retention system (such as a structural member containing a drug and a carrier polymer, a coupling member, a time-dependent polymer linker, or a central structural member), which can also contain PCL, which can be the same PCL as the PCL in the enteric polymer linker or a different PCL from the PCL in the enteric polymer linker, and which can have the same concentration or a different concentration. The different PCLs in the enteric polymer linker and another member directly connected or bonded to the enteric linker can be different, for example, the weight average molecular weight of PCL, the intrinsic viscosity of PCL, or the ratio of PCL (for example, when using a blend of two or more PCL polymers). In some embodiments, the enteric disintegration matrix contains about 30 wt% - about 40 wt% of PCL. In some embodiments, the enteric disintegration matrix contains about 32 wt% - about 37 wt% of PCL. In some embodiments, the enteric disintegration matrix contains about 34 wt% of PCL. In some embodiments, the enteric disintegration matrix contains about 33.95 wt% of PCL.

[0135] The enteric disintegration matrix may also comprise one or more plasticizers, such as poloxamer (e.g., poloxamer 407 or "P407"). In some embodiments, the enteric disintegration matrix comprises from about 0.5 wt% to about 5 wt% of poloxamer. In some embodiments, the enteric disintegration matrix comprises from about 1 wt% to about 3 wt% of poloxamer. In some embodiments, the enteric disintegration matrix comprises about 2 wt% of poloxamer.

[0136] In some embodiments, the enteric disintegration matrix comprises a color-absorbing dye (also referred to as a colorant or pigment). A color-absorbing dye may be included to enhance the connection or attachment of the polymeric joint to other components of the gastric retention system. The color-absorbing dye may absorb heat during laser welding, infrared welding, or other heat-induced attachment, which increases the tensile strength of the resulting connection. Exemplary color-absorbing dyes include iron oxide and carbon black. The enteric polymer joint may comprise up to about 5%, such as up to about 4%, up to about 3%, up to about 2%, up to about 1%, up to about 0.5%, up to about 0.3%, up to about 0.2%, or up to about 0.1% by weight of the color-absorbing dye. In some embodiments, the enteric disintegration matrix comprises from about 0.01 wt% to about 0.2 wt% of the color-absorbing dye E172. In some embodiments, the enteric disintegration matrix comprises from about 0.05 wt% to about 0.15 wt% of the color-absorbing dye E172. In some embodiments, the enteric disintegration matrix comprises about 0.1 wt% of the color-absorbing dye E172.

[0137] In some embodiments, the enteric disintegration matrix comprises from about 59 wt% to about 69 wt% of HPMCAS, from about 29 wt% to about 39 wt% of PCL, and from about 0.5 wt% to about 5 wt% of poloxamer (e.g., P407). Optionally, the enteric disintegration matrix further comprises iron oxide, such as from about 0.01 wt% to about 0.2 wt% of iron oxide (e.g., E172).

[0138] In some embodiments, the enteric disintegration matrix comprises from about 62 wt% to about 66 wt% of HPMCAS, from about 32 wt% to about 36 wt% of PCL, and from about 1 wt% to about 3 wt% of poloxamer (e.g., P407). Optionally, the enteric disintegration matrix further comprises iron oxide, such as from about 0.05 wt% to about 0.15 wt% of iron oxide (e.g., E172).

[0139] In some embodiments, the enteric disintegration matrix comprises about 63.95 wt% of HPMCAS, about 33.95 wt% of PCL, and about 2 wt% of poloxamer (e.g., P407). Optionally, the enteric disintegration matrix further comprises iron oxide, such as about 0.1 wt% of iron oxide (e.g., E172).

[0140] In some embodiments, the enteric disintegrating matrix comprises from about 59 wt% to about 69 wt% HPMCAS, from about 29 wt% to about 39 wt% PCL, and from about 0.5 wt% to about 5 wt% poloxamer (e.g., P407).

[0141] In some embodiments, the enteric disintegrating matrix comprises from about 62 wt% to about 66 wt% HPMCAS, from about 32 wt% to about 36 wt% PCL, and from about 1 wt% to about 3 wt% poloxamer (e.g., P407).

[0142] In some embodiments, the enteric disintegrating matrix comprises about 64 wt% HPMCAS, about 34 wt% PCL, and about 2 wt% poloxamer (e.g., P407).

[0143] In some embodiments, the dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a pH-dependent disintegrating matrix, and the pH-dependent disintegrating matrix comprises about 33.95 wt% polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g to about 2.1 dl / g, such as Corbion PC17. In some embodiments, the gastric retention system comprises a pH-dependent disintegrating matrix, and the pH-dependent disintegrating matrix comprises about 63.95 wt% hydroxypropyl methylcellulose acetate succinate, such as HPMCAS-MG. In some embodiments, the gastric retention system comprises a pH-dependent disintegrating matrix, and the pH-dependent disintegrating matrix comprises about 2.0 wt% poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(O-CH(CH3)CH2)y-(OCH2CH2)z-OH, wherein x and z are about 101 and y is about 56, such as poloxamer 407 (P407, a poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer having a polyoxypropylene molecular weight of about 4000 and a polyoxyethylene content of about 70%). In some embodiments, the gastric retention system comprises a pH-dependent disintegrating matrix, and the pH-dependent disintegrating matrix comprises about 0.1 wt% iron oxide, such as E172. In some embodiments, the dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a pH-dependent disintegrating matrix, and the pH-dependent disintegrating matrix comprises about 33.95 wt% Corbion PC17, about 63.95 wt% HPMCAS-MG, about 2.0 wt% P407, and about 0.1 wt% E172.

[0144] Exemplary amounts of the components for the enteric disintegrating matrix are provided in the table below. The amounts are given as approximate weight percentages and it is understood that when ranges are provided, the amounts are selected so as to total 100%.

[0145]

[0146] In some embodiments, the dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a pH-dependent disintegrating matrix, and the pH-dependent disintegrating matrix comprises about 34 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g to about 2.1 dl / g, such as Corbion PC17. In some embodiments, the gastric retention system comprises a pH-dependent disintegrating matrix, and the pH-dependent disintegrating matrix comprises about 64 wt% of hypromellose acetate succinate, such as HPMCAS-MG. In some embodiments, the gastric retention system comprises a pH-dependent disintegrating matrix, and the pH-dependent disintegrating matrix comprises about 2.0 wt% of a poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(O-CH(CH3)CH2)y-(OCH2CH2)z-OH, where x and z are about 101 and y is about 56, such as poloxamer 407 (P407, a poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer having a polyoxypropylene molecular weight of about 4000 and a polyoxyethylene content of about 70%). In some embodiments, the dosage form for administering one or more active agents comprises a gastric retention system, wherein the gastric retention system comprises a pH-dependent disintegrating matrix, and the pH-dependent disintegrating matrix comprises about 34 wt% of Corbion PC17, about 64 wt% of HPMCAS-MG, and about 2.0 wt% of P407.

[0147] Exemplary amounts of components for enteric disintegrating matrices are provided in the table below. The amounts are given in approximate weight percentages and it is understood that when ranges are provided, the amounts are selected such that the total amounts to 100%.

[0148] Enteric disintegration matrix (E-DM2) Formulation 1 Formulation 2 Formulation 3 PCL (e.g., PC17 with midpoint viscosity 1.7 dl / g) 29-39 32-36 34 HPMCAS 59-69 62-66 64 P407 0.5-5 1-3 2

[0149] Disintegrating filament

[0150] In some embodiments, the gastric retention system comprises arms connected by one or more filaments. In some embodiments, the filaments are degradable filaments. In some embodiments, the gastric retention system comprises arms connected at the distal end by one or more filaments. In some embodiments, the filaments connect the arms in a circumferential direction. In some embodiments, the filaments are degradable filaments. In some embodiments, the filaments comprise one or more of poly(lactic-co-glycolic acid), polyglycolic acid, polylactic acid, polydioxanone, polycaprolactone, polytrimethylene carbonate, cellulose, or any blends and copolymers thereof. In some embodiments, the filaments comprise poly(lactic-co-glycolic acid). In some embodiments, the filaments comprise polyglycolic acid. In some embodiments, the thickness of the filaments is any one of about 0.05 mm, 0.1 mm, 0.15 mm, 0.20 mm, 0.25 mm, 0.30 mm, 0.35 mm, 0.40 mm, 0.45 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.0 mm, or any thickness therebetween. In some embodiments, the thickness of the filaments is about 0.20 mm. In some embodiments, the thickness of the filaments is about 0.30 mm. In some embodiments, the filaments are Bondek Suture 2-0. In some embodiments, the filaments are Bondek Suture 3-0.

[0151] Additional degradable matrix as the tip of the arm

[0152] In some embodiments, in addition to the time-dependent degradable matrix and enteric degradable matrix, the gastric retention system further comprises arms containing a third degradable matrix. In some embodiments, the third degradable matrix is the filament retention section (i.e., the section to which the filaments are attached). In some embodiments, the third degradable matrix is the distal section of the retention system arm, i.e., the tip of the arm. In some embodiments, the third degradable matrix is referred to as the outer degradable matrix tip enteric PCL (ODMTEP).

[0153] In some embodiments, the third degradable matrix comprises hydroxypropyl methylcellulose acetate succinate (HPMCAS). For example, in some embodiments, the third degradable matrix comprises about 60 wt% - about 70 wt% of HPMCAS. In some embodiments, the third degradable matrix comprises about 63 wt% - about 67 wt% of HPMCAS. In some embodiments, the third degradable matrix comprises about 64.9 wt% of HPMCAS.

[0154] In some embodiments, the third disintegration matrix comprises a polymer common to one or the other segment in the gastric retention system arm. In some embodiments, the third disintegration matrix comprises polycaprolactone (PCL). In some embodiments, the third disintegration matrix comprises from about 25 wt% to about 35 wt% of PCL. In some embodiments, the third disintegration matrix comprises from about 28 wt% to about 32 wt% of PCL. In some embodiments, the third disintegration matrix comprises about 30 wt% of PCL.

[0155] In some embodiments, the third disintegration matrix comprises one or more acids, such as stearic acid. In some embodiments, the third disintegration matrix comprises from about 1 wt% to about 5 wt% of stearic acid. In some embodiments, the third disintegration matrix comprises from about 2 wt% to about 3 wt% of stearic acid. In some embodiments, the third disintegration matrix comprises about 2.5 wt% of stearic acid.

[0156] In some embodiments, the third disintegration matrix may further comprise one or more plasticizers, such as propylene glycol. In some embodiments, the third disintegration matrix comprises from about 1 wt% to about 5 wt% of propylene glycol. In some embodiments, the third disintegration matrix comprises from about 2 wt% to about 3 wt% of propylene glycol. In some embodiments, the third disintegration matrix comprises about 2.5 wt% of propylene glycol.

[0157] In some embodiments, the third disintegration matrix includes a color-absorbing dye (also referred to as a colorant or pigment). A color-absorbing dye may be included to enhance the connection or attachment of the polymer joint to other gastric retention system components. The color-absorbing dye can absorb heat during laser welding, infrared welding, or other heat-induced attachment, which increases the tensile strength of the resulting connection. Exemplary color-absorbing dyes include iron oxide and carbon black. The third disintegration matrix may include a color-absorbing dye in an amount of up to about 5%, such as up to about 4%, up to about 3%, up to about 2%, up to about 1%, up to about 0.5%, up to about 0.3%, up to about 0.2%, or up to about 0.1%. In some embodiments, the third disintegration matrix comprises from about 0.01 wt% to about 0.5 wt% of a color-absorbing dye. In some embodiments, the third disintegration matrix comprises from about 0.05 wt% to about 0.15 wt% of a color-absorbing dye. In some embodiments, the third disintegration matrix comprises about 0.1 wt% of a color-absorbing dye. In some embodiments, the third disintegration matrix comprises about 0.025% iron oxide and about 0.075% FD&C Red 40. In some embodiments, the third disintegration matrix comprises about 0.025% iron oxide and about 0.075% FD&C Red 40.

[0158] In some embodiments, the third disintegration matrix comprises from about 60 wt% to about 70 wt% HPMCAS, from about 25 wt% to about 35 wt% PCL, from about 1 wt% to about 5 wt% propylene glycol, and from about 1 wt% to about 5 wt% stearic acid. Optionally, the third disintegration matrix further comprises from about 0.01 wt% to about 0.5 wt% iron oxide.

[0159] In some embodiments, the third disintegration matrix comprises from about 63 wt% to about 67 wt% HPMCAS, from about 28 wt% to about 32 wt% PCL, from about 2 wt% to about 3 wt% propylene glycol, and from about 2 wt% to about 3 wt% stearic acid. Optionally, the third disintegration matrix further comprises from about 0.05 wt% to about 0.15 wt% iron oxide.

[0160] In some embodiments, the third disintegration matrix comprises 64.9 wt% HPMCAS, about 30 wt% PCL, about 2.5 wt% propylene glycol, and about 2.5 wt% stearic acid. Optionally, the third disintegration matrix further comprises about 0.1 wt% iron oxide, such as about 0.025% iron oxide black and about 0.075% FD&C Red 40.

[0161] Exemplary amounts of the components for the third disintegration matrix are provided in the table below. The amounts are given as approximate percentages and it should be understood that when ranges are provided, the amounts are selected such that the total amounts to 100%.

[0162]

[0163] Inert segment

[0164] In some embodiments, the gastric retention system comprises one or more inert segments. In some embodiments, the inert segment comprises one or more radiopaque substances.

[0165] In some embodiments, the inert segment comprises a polymer common to other segments in the gastric retention system. In some embodiments, the inert segment comprises polycaprolactone (PCL). In some embodiments, the inert segment comprises from about 61 wt% to about 71 wt% PCL. In some embodiments, the inert segment comprises from about 64 wt% to about 69 wt% PCL. In some embodiments, the inert segment comprises about 66.5 wt% PCL. In some embodiments, the inert segment comprises about 66.45 wt% PCL.

[0166] In some embodiments, the inert segment comprises a vinylpyrrolidone-vinyl acetate copolymer in a mass ratio of 6:4 (i.e., copovidone, such as Kollidon VA64). In some embodiments, the inert segment comprises from about 27 wt% to about 37 wt% of copovidone. In some embodiments, the inert segment comprises from about 30 wt% to about 34 wt% of copovidone. In some embodiments, the inert segment comprises about 32 wt% of copovidone.

[0167] The inert segment may further include one or more plasticizers, such as poloxamer (e.g., poloxamer 407 or "P407"). In some embodiments, the inert segment comprises from about 0.2 wt% to about 4 wt% of poloxamer. In some embodiments, the inert segment comprises from about 0.5 wt% to about 2.5 wt% of poloxamer. In some embodiments, the inert segment comprises about 1.5 wt% of poloxamer.

[0168] In some embodiments, the inert segment includes a color-absorbing dye (also referred to as a colorant or pigment). The inert segment may include a color-absorbing dye in an amount of up to about 5%, such as up to about 4%, up to about 3%, up to about 2%, up to about 1%, up to about 0.5%, up to about 0.3%, up to about 0.2%, up to about 0.1%, or up to 0.05%. In some embodiments, the inert segment comprises from about 0.005 wt% to about 0.2 wt% of the color-absorbing dye. In some embodiments, the inert segment comprises from about 0.01 wt% to about 0.1 wt% of the color-absorbing dye. In some embodiments, the inert segment comprises about 0.05 wt% of the color-absorbing dye. In some embodiments, the color-absorbing dye is FD&C Blue #1.

[0169] In some embodiments, the inert segment comprises from about 61 wt% to about 71 wt% of PCL, from about 27 wt% to about 37 wt% of copovidone, and from about 0.2 wt% to about 4 wt% of poloxamer. Optionally, the inert segment further comprises a color-absorbing dye, such as from about 0.005 wt% to about 0.2 wt% of the color-absorbing dye FD&C Blue #1.

[0170] In some embodiments, the inert segment comprises from about 64 wt% to about 69 wt% of PCL, from about 30 wt% to about 34 wt% of copovidone, and from about 0.5 wt% to about 2.5 wt% of poloxamer. Optionally, the inert segment further comprises a color-absorbing dye, such as from about 0.01 wt% to about 0.1 wt% of the color-absorbing dye FD&C Blue #1.

[0171] In some embodiments, the inert segment comprises about 66.45 wt% PCL, about 32 wt% copovidone, and about 1.5 wt% poloxamer. Optionally, the inert segment further comprises a color-absorbing dye, such as about 0.05 wt% of the color-absorbing dye FD&C Blue #1.

[0172] The following table provides exemplary amounts of the components of one embodiment of an inert segment (e.g., an inactive spacer). The amounts are given in approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected so as to total 100%.

[0173]

[0174] In some embodiments, the inert segment comprises a polymer common to other segments in the gastric retention system. In some embodiments, the inert segment comprises polycaprolactone (PCL). In some embodiments, the inert segment comprises from about 35 wt% to about 45 wt% PCL. In some embodiments, the inert segment comprises from about 38 wt% to about 42 wt% PCL. In some embodiments, the inert segment comprises about 40 wt% PCL. In some embodiments, the inert segment comprises about 33.995 wt% PCL.

[0175] In some embodiments, the inert segment comprises a vinylpyrrolidone-vinyl acetate copolymer in a mass ratio of 6:4 (i.e., copovidone, such as Kollidon VA64). In some embodiments, the inert segment comprises from about 37 wt% to about 47 wt% copovidone. In some embodiments, the inert segment comprises from about 40 wt% to about 44 wt% copovidone. In some embodiments, the inert segment comprises about 42 wt% copovidone.

[0176] The inert segment may further include one or more plasticizers, such as poloxamer (e.g., poloxamer 407 or "P407"). In some embodiments, the inert segment comprises from about 1 wt% to about 5 wt% poloxamer. In some embodiments, the inert segment comprises from about 2 wt% to about 4 wt% poloxamer. In some embodiments, the inert segment comprises about 3 wt% poloxamer.

[0177] The inert segment may include one or more plasticizers, such as polyethylene glycol. The term "polyethylene glycol" may be used interchangeably with the terms "polyoxyethylene" and "PEO" herein. In some embodiments, the molecular weight of the polyethylene glycol is about 90K - about 110K, such as 100k (also referred to as 100K or 100 kDa). In some embodiments, the inert segment comprises polyethylene glycol having a molecular weight of about 100k (polyethylene glycol 100k). In some embodiments, the inert segment comprises about 10 wt% - about 20 wt% of polyethylene glycol 100k. In some embodiments, the inert segment comprises about 13 wt% - about 17 wt% of polyethylene glycol 100k. In some embodiments, the inert segment comprises about 15 wt% of polyethylene glycol 100k.

[0178] In some embodiments, the inert segment includes a color-absorbing dye (also referred to as a colorant or pigment). In some embodiments, the inert segment may include a color-absorbing dye in an amount of up to about 1%, such as up to about 0.5%, up to about 0.4%, up to about 0.3%, up to about 2%, up to about 1%, up to about 0.5%, up to about 0.3%, up to about 0.2%, up to about 0.1% or up to 0.005%. In some embodiments, the inert segment comprises about 0.0005 wt% - about 0.2 wt% of a color-absorbing dye. In some embodiments, the inert segment comprises about 0.001 wt% - about 0.01 wt% of a color-absorbing dye. In some embodiments, the inert segment comprises about 0.005 wt% of a color-absorbing dye. In some embodiments, the color-absorbing dye is iron oxide (such as E172).

[0179] In some embodiments, the inert segment comprises about 35 wt% - about 45 wt% of PCL, about 37 wt% - about 47 wt% of crospovidone, about 10 wt% - about 20 wt% of polyethylene glycol, such as polyethylene glycol having an average molecular weight of 100,000, such as PEO 100K and about 1 wt% - about 5 wt% of poloxamer. Optionally, the inert segment further comprises a color-absorbing dye, such as about 0.0005 wt% - about 0.02 wt% of the color-absorbing dye E172.

[0180] In some embodiments, the inert segment comprises about 38 wt% - about 42 wt% of PCL, about 40 wt% - about 44 wt% of crospovidone, about 13 wt% - about 17 wt% of polyethylene glycol, such as polyethylene glycol having an average molecular weight of 100,000, such as PEO 100K, about 2 wt% - about 4 wt% of poloxamer. Optionally, the inert segment further comprises a color-absorbing dye, such as about 0.001 wt% - about 0.01 wt% of the color-absorbing dye E172.

[0181] In some embodiments, the inert segment comprises about 39.995 wt% PCL, about 42 wt% copovidone, about 15 wt% PEO100K, and about 3 wt% poloxamer. Optionally, the inert segment further comprises a color-absorbing dye, such as about 0.005 wt% color-absorbing dye E172.

[0182] The following table provides exemplary amounts of the components of one embodiment of an inert segment (e.g., an inactive spacer). The amounts are given as approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected so as to total 100%.

[0183]

[0184] In some embodiments, the gastric retention system comprises one or more inert segments, wherein the inert segment comprises one or more radiopaque substances. In some embodiments, the gastric retention system comprises an inert segment, wherein the inert segment is a radiopaque segment.

[0185] In some embodiments, the inert segment comprises a polymer that is common with other segments in the gastric retention system. In some embodiments, the inert segment comprises polycaprolactone (PCL). In some embodiments, the inert segment comprises about 65 wt% - about 75 wt% PCL. In some embodiments, the inert segment comprises about 68 wt% - about 72 wt% PCL. In some embodiments, the inert segment comprises about 70 wt% PCL.

[0186] In some embodiments, the inert segment comprises a radiopaque substance. In some embodiments, the inert segment comprises a radiopaque substance, wherein the radiopaque substance is (BiO)2CO3. In some embodiments, the inert segment comprises (BiO)2CO3. In some embodiments, the inert segment comprises about 25 wt% - about 35 wt% (BiO)2CO3. In some embodiments, the inert segment comprises about 28 wt% - about 32 wt% (BiO)2Co3. In some embodiments, the inert segment comprises about 30 wt% (BiO)2Co3.

[0187] In some embodiments, the inert segment comprises about 65 wt% - about 75 wt% PCL and about 25 wt% - about 35 wt% (BiO)2Co3. In some embodiments, the inert segment comprises about 68 wt% - about 72 wt% PCL and about 28 wt% - about 32 wt% (BiO)2Co3. In some embodiments, the inert segment comprises about 70 wt% PCL and about 30 wt% (BiO)2Co3.

[0188] Exemplary amounts of the components of one embodiment of the inert segment (e.g., rPCL segment) are provided in the table below. The amounts are given as approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected so as to total 100%.

[0189] Inert segment - rPCL (radiopaque) IS-3 Formulation 1 Formulation 2 Formulation 3 PCL (e.g., PC17 with midpoint viscosity 1.7 dl / g) 65-75 68-72 70 <![CDATA[(BiO)2CO3]]> 25-35 28-32 30

[0190] Carrier polymer - active agent segment (drug - eluting segment)

[0191] During the time the gastric retention system resides in the stomach, the carrier polymer - active agent segment or drug - eluting segment releases the active agent in a controlled manner. The carrier polymer is blended with the active agent and a segment is formed, which is then assembled with other components herein to prepare the gastric retention system. Compositions of such carrier polymer - active agent blends are provided below for specific pharmaceutical formulations (including risperidone).

[0192] In some embodiments, the dosage form for administering risperidone comprises a gastric retention system that comprises from about 10 mg to about 35 mg of risperidone. In some embodiments, the dosage form for administering risperidone comprises a gastric retention system that comprises from about 10 mg to about 20 mg of risperidone. In some embodiments, the dosage form for administering risperidone comprises a gastric retention system that comprises about 14 mg of risperidone. In some embodiments, the dosage form for administering risperidone comprises a gastric retention system that comprises from about 20 mg to about 35 mg of risperidone. In some embodiments, the dosage form comprises a gastric retention system, wherein the gastric retention system comprises about 28 mg of risperidone.

[0193] In some embodiments, the dosage form comprises a gastric retention system, wherein the gastric retention system comprises a drug eluting segment, and the drug eluting segment comprises about 14 mg of risperidone. In some embodiments, the dosage form comprises a gastric retention system, wherein the gastric retention system comprises a drug eluting segment, and the drug eluting segment comprises about 28 mg of risperidone. In some embodiments, wherein the drug eluting segment comprises about 30 wt% - about 40 wt% of risperidone, the drug eluting segment comprises about 51 wt% - about 61 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the drug eluting segment comprises about 2 wt% - about 8 wt% of vinyl pyrrolidone-vinyl acetate copolymer, such as Kollidon VA64. In some embodiments, the drug eluting segment comprises about 1 wt% - about 5 wt% of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(O-CH(CH3)CH2)y-(OCH2CH2)z-OH, where x and z are about 101, and y is about 56, such as poloxamer 407. In some embodiments, the drug eluting segment comprises about 0.1 wt% - about 1 wt% of vitamin E succinate. In some embodiments, the drug eluting segment comprises about 0.1 wt% - about 1 wt% of colloidal silica (SiO2). In some embodiments, the drug eluting segment comprises about 0.01 wt% - about 0.5 wt% of pigment.

[0194] In some embodiments, wherein the drug eluting segment comprises about 33 wt% - about 37 wt% of risperidone, the drug eluting segment comprises about 54 wt% - about 58 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the drug eluting segment comprises about 4 wt% - about 6 wt% of vinyl pyrrolidone-vinyl acetate copolymer, such as Kollidon VA64. In some embodiments, the drug eluting segment comprises about 2 wt% - about 4 wt% of poly(ethylene glycol) block-poly(propylene glycol) block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(v-CH(CH3)CH2)y-(OCH2CH2)z-OH, where x and z are about 101, and y is about 56, such as poloxamer 407. In some embodiments, the drug eluting segment comprises about 0.2 wt% - about 0.8 wt% of vitamin E succinate. In some embodiments, the drug eluting segment comprises about 0.2 wt% - about 0.8 wt% of colloidal silica (SiO2). In some embodiments, the drug eluting segment comprises about 0.05 wt% - about 0.2 wt% of pigment.

[0195] In some embodiments, where the drug eluting segment comprises about 35 wt% risperidone, the drug eluting segment comprises about 55.9 wt% polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the drug eluting segment comprises about 5.0 wt% vinylpyrrolidone-vinyl acetate copolymer, such as Kollidon VA64. In some embodiments, the drug eluting segment comprises about 3.0 wt% poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(O-CH(CH3)CH2)y-(OCH2CH2)z-OH, where x and z are about 101, and y is about 56, such as poloxamer 407. In some embodiments, the drug eluting segment comprises about 0.5 wt% vitamin E succinate. In some embodiments, the drug eluting segment comprises about 0.5 wt% colloidal silica (SiO2). In some embodiments, the drug eluting segment comprises about 0.1 wt% pigment.

[0196] In some embodiments, the pigment comprises aluminum complex of 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-((4-sulfophenyl)azo)-1H-pyrazole-3-carboxylic acid, such as FD&C Yellow No. 5 Aluminum Lake, in an amount of about 0.05 wt% of the total weight of the drug eluting segment; and N-ethyl-N-(4-((4-(ethyl((3-sulfophenyl)methyl)amino)phenyl)(2-sulfophenyl)methylene)-2,5-cyclohexadien-1-ylidene)benzenemethanaminium, such as FD&C Blue No. 1 Aluminum Lake, in an amount of 0.05 wt% of the total weight of the drug eluting segment. FD&C Yellow No. 5 Aluminum Lake and FD&C Blue No. 1 Aluminum Lake are approved food coloring additives. In some embodiments, the amount of the dye in FD&C Yellow No. 5 Aluminum Lake is about 14 - 16% by weight. In some embodiments, the amount of the dye in FD&C Blue No. 1 Aluminum Lake is about 11 - 13% by weight.

[0197] In some embodiments, the drug eluting segment comprises about 30 wt% - about 40 wt% risperidone, about 51 wt% - about 61 wt% PCL, about 2 wt% - about 8 wt% VA64, about 1 wt% - about 5 wt% P407, about 0.1 wt% - about 1 wt% vitamin E succinate, about 0.1 wt% - about 1 wt% SiO2, and about 0.01 wt% - about 0.5 wt% pigment.

[0198] In some embodiments, the drug eluting segment comprises from about 33 wt% to about 37 wt% of risperidone, from about 54 wt% to about 58 wt% of PCL, from about 4 wt% to about 6 wt% of VA64, from about 2 wt% to about 4 wt% of P407, from about 0.2 wt% to about 0.8 wt% of vitamin E succinate, from about 0.2 wt% to about 0.8 wt% of Sio2 and from about 0.05 wt% to about 0.15 wt% of a pigment.

[0199] In some embodiments, the drug eluting segment comprises about 35.0 wt% of risperidone, about 55.9 wt% of PCL, about 5.0 wt% of VA64, about 3.0 wt% of P407, about 0.5 wt% of vitamin E succinate, about 0.5 wt% of Sio2 and about 0.1 wt% of a pigment. In some embodiments, the pigment comprises an amount of FD&C Yellow No. 5 Aluminum Lake of about 0.05 wt% of the total weight of the drug eluting segment and an amount of FD&C Blue No. 1 Aluminum Lake of about 0.05 wt% of the total weight of the drug eluting segment. FD&C Yellow No. 5 Aluminum Lake and FD&C Blue No. 1 Aluminum Lake are approved food coloring additives. In some embodiments, the amount of dye in FD&C Yellow No. 5 Aluminum Lake is about 14 - 16% by weight. In some embodiments, the amount of dye in FD&C Blue No. 1 Aluminum Lake is about 11 - 13% by weight. The following table provides exemplary amounts of the components of one embodiment of the carrier polymer - arm segment (drug eluting segment). The amounts are given as approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected so as to total 100%. "Pharm.accept.salt" means its pharmaceutically acceptable salt.

[0200]

[0201] The above drug eluting segment, although described as being risperidone formulated, is not so limited and can be used with other drugs by replacing some or all of the risperidone component and / or other components with other drugs.

[0202] In some embodiments, the dosage form for administering risperidone comprises a gastric retention system, and the gastric retention system comprises about 12 mg - about 60 mg of risperidone. In some embodiments, the dosage form for administering risperidone comprises a gastric retention system, and the gastric retention system comprises about 12 mg - about 36 mg of risperidone. In some embodiments, the dosage form for administering risperidone comprises a gastric retention system, and the gastric retention system comprises about 12 mg - about 20 mg of risperidone. In some embodiments, the dosage form for administering risperidone comprises a gastric retention system, and the gastric retention system comprises about 16 mg of risperidone. In some embodiments, the dosage form for administering risperidone comprises a gastric retention system, and the gastric retention system comprises about 28 mg - about 36 mg of risperidone. In some embodiments, the dosage form comprises a gastric retention system, wherein the gastric retention system comprises about 32 mg of risperidone. In some embodiments, the dosage form for administering risperidone comprises a gastric retention system, and the gastric retention system comprises about 44 mg - about 52 mg of risperidone. In some embodiments, the dosage form comprises a gastric retention system, wherein the gastric retention system comprises about 48 mg of risperidone.

[0203] In some embodiments, the dosage form comprises a gastric retention system, wherein the gastric retention system comprises a drug eluting segment, and the drug eluting segment comprises about 16 mg of risperidone. In some embodiments, the dosage form comprises a gastric retention system, wherein the gastric retention system comprises a drug eluting segment, and the drug eluting segment comprises about 32 mg of risperidone. In some embodiments, wherein the drug eluting segment comprises about 30 wt% - about 40 wt% of risperidone, the drug eluting segment comprises about 51 wt% - about 61 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the drug eluting segment comprises about 2 wt% - about 8 wt% of vinylpyrrolidone-vinyl acetate copolymer, such as Kollidon VA64. In some embodiments, the drug eluting segment comprises about 1 wt% - about 5 wt% of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(O-CH(CH3)CH2)y-(OCH2CH2)z-OH, wherein x and z are about 101, and y is about 56, such as poloxamer 407. In some embodiments, the drug eluting segment comprises about 0.1 wt% - about 1 wt% of vitamin E succinate. In some embodiments, the drug eluting segment comprises about 0.1 wt% - about 1 wt% of colloidal silica (SiO2). In some embodiments, the drug eluting segment comprises about 0.01 wt% - about 0.5 wt% of pigment.

[0204] In some embodiments, wherein the drug eluting segment comprises from about 33 wt% to about 37 wt% of risperidone, the drug eluting segment comprises from about 54 wt% to about 58 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of from about 1.5 dl / g to about 2.1 dl / g, such as Corbion PC17. In some embodiments, the drug eluting segment comprises from about 4 wt% to about 6 wt% of vinyl pyrrolidone - vinyl acetate copolymer. Such as Kollidon VA64. In some embodiments, the drug eluting segment comprises from about 2 wt% to about 4 wt% of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(O-CH(CH3)CH2)y-(OCH2CH2)z-OH, wherein x and z are about 101, and y is about 56, such as poloxamer 407. In some embodiments, the drug eluting segment comprises from about 0.2 wt% to about 0.8 wt% of vitamin E succinate. In some embodiments, the drug eluting segment comprises from about 0.2 wt% to about 0.8 wt% of colloidal silica (SiO2). In some embodiments, the drug eluting segment comprises from about 0.05 wt% to about 0.2 wt% of pigment.

[0205] In some embodiments, wherein the drug eluting segment comprises about 35 wt% of risperidone, the drug eluting segment comprises about 55.9 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of from about 1.5 dl / g to about 2.1 dl / g, such as Corbion PC17. In some embodiments, the drug eluting segment comprises about 5.0 wt% of vinyl pyrrolidone - vinyl acetate copolymer. Such as Kollidon VA64. In some embodiments, the drug eluting segment comprises about 3.0 wt% of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(O-CH(CH3)CH2)y-(OCH2CH2)z-OH, wherein x and z are about 101, and y is about 56, such as poloxamer 407. In some embodiments, the drug eluting segment comprises about 0.5 wt% of vitamin E succinate. In some embodiments, the drug eluting segment comprises about 0.5 wt% of colloidal silica (SiO2). In some embodiments, the drug eluting segment comprises about 0.1 wt% of pigment.

[0206] In some embodiments, the pigment comprises aluminum 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-((4-sulfophenyl)azo)-1H-pyrazole-3-carboxylate, such as FD&C Yellow 5 Aluminum Lake, in an amount of about 0.05 wt% of the total weight of the drug eluting segment; N-ethyl-N-(4-((4-(ethyl((3-sulfophenyl)methyl)amino)phenyl)(2-sulfophenyl)methylene)-2,5-cyclohexadien-1-ylidene)benzenemethanaminium, such as FD&C Blue 1 Aluminum Lake, in an amount of 0.05 wt% of the total weight of the drug eluting segment. FD&C Yellow 5 Aluminum Lake and FD&C Blue 1 Aluminum Lake are approved food coloring additives. In some embodiments, the amount of dye in FD&C Yellow 5 Aluminum Lake is about 14 - 16% by weight. In some embodiments, the amount of dye in FD&C Blue 1 Aluminum Lake is about 11 - 13% by weight.

[0207] In some embodiments, the drug eluting segment comprises about 30 wt% - about 40 wt% of risperidone, about 51 wt% - about 61 wt% of PCL, about 2 wt% - about 8 wt% of VA64, about 1 wt% - about 5 wt% of P407, about 0.1 wt% - about 1 wt% of vitamin E succinate, about 0.1 wt% - about 1 wt% of SiO2, and about 0.01 wt% - about 0.5 wt% of pigment.

[0208] In some embodiments, the drug eluting segment comprises about 33 wt% - about 37 wt% of risperidone, about 54 wt% - about 58 wt% of PCL, about 4 wt% - about 6 wt% of VA64, about 2 wt% - about 4 wt% of P407, about 0.2 wt% - about 0.8 wt% of vitamin E succinate, about 0.2 wt% - about 0.8 wt% of SiO2, and about 0.05 wt% - about 0.15 wt% of pigment.

[0209] In some embodiments, the drug eluting segment comprises about 35.0 wt% of risperidone, about 55.9 wt% of PCL, about 5.0 wt% of VA64, about 3.0 wt% of P407, about 0.5 wt% of vitamin E succinate, about 0.5 wt% of SiO2, and about 0.1 wt% of pigment. In some embodiments, the pigment comprises FD&C Yellow 5 Aluminum Lake in an amount of about 0.05 wt% of the total weight of the drug eluting segment and FD&C Blue 1 Aluminum Lake in an amount of 0.05 wt% of the total weight of the drug eluting segment. FD&C Yellow 5 Aluminum Lake and FD&C Blue 1 Aluminum Lake are approved food coloring additives. In some embodiments, the amount of dye in FD&C Yellow 5 Aluminum Lake is about 14 - 16% by weight. In some embodiments, the amount of dye in FD&C Blue 1 Aluminum Lake is about 11 - 13% by weight.

[0210] Exemplary amounts of the components of one embodiment of the carrier polymer-arm segment (drug eluting segment) are provided in the table below. The amounts are given as approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected so as to total 100%. “Pharm.accept.salt” means pharmaceutically acceptable salt.

[0211]

[0212]

[0213] Although the above drug eluting segment is described as being formulated with risperidone, it is not limited thereto and can be used with other drugs by replacing some or all of the risperidone components and / or other components with other drugs.

[0214] In some embodiments, the star-shaped dosage form for administering risperidone can include arms, which in turn include 1) a carrier polymer-active agent arm segment; 2) an inactive arm segment; 3) one or more enteric linkers; 4) one or more time-dependent linkers; 5) a rate-modulating release film; and / or 6) other optional spacers. The arms are connected to an elastomeric core in a star-shaped device arrangement. Typically, six arms are used for the star-shaped dosage form. In some embodiments, where six arms are used for the star-shaped dosage form, any one of 1, 2, 3, 4, 5, or 6 arms includes the carrier polymer-active agent arm segment. In some embodiments, where six arms are used for the star-shaped dosage form, 3 arms include the carrier polymer-active agent arm segment. In some embodiments, where six arms are used for the star-shaped dosage form, 6 arms include the carrier polymer-active agent arm segment.

[0215] The carrier polymer-active agent arm segment of the risperidone dosage form may comprise risperidone (or a pharmaceutically acceptable salt thereof), polycaprolactone, copovidone (VA64), poloxamer 407 (P407), silicon dioxide (SiO2), vitamin E succinate (vitE), and an optional colorant. The calcium salt of risperidone may be used for the carrier polymer-active agent arm segment. The viscosity of the polycaprolactone used may be from about 1.5 dl / g to about 1.9 dl / g, such as about 1.7 dl / g. Any pharmaceutically acceptable colorant may be used. Examples of colorants that may be used include FD&C Red No. 40 aluminum lake, FD&C Yellow No. 5 aluminum lake, or an approximately equal blend of both. In some embodiments, typically six arms are used for the star-shaped dosage form, and 1, 2, 3, 4, 5, or 6 arms comprise the carrier polymer-active agent arm segment. In some embodiments, 3 arms comprise the carrier polymer-active agent arm segment. In some embodiments, 6 arms comprise the carrier polymer-active agent arm segment. In some embodiments, the total amount of active agent contained in the dosage form is 1, 2, 3, 4, 5, or 6 times the amount of active agent contained in a single arm. In some embodiments, the total amount of active agent contained in the dosage form is 3 times the amount of active agent contained in a single arm. In some embodiments, the total amount of active agent contained in the dosage form is 6 times the amount of active agent contained in a single arm. The total weight of risperidone, a pharmaceutically acceptable salt of risperidone, or the calcium salt of risperidone in the star-shaped dosage form may be from about 2 mg to about 50 mg, such as from about 4 mg to about 30 mg, or from about 10 mg to about 20 mg, or from about 20 mg to about 30 mg, or from about 25 mg to about 35 mg, or from about 12 mg to about 16 mg, or from about 26 mg to about 30 mg, or from about 3 mg to about 5 mg, or from about 8 mg to about 10 mg, or from about 13 mg to about 15 mg, or from about 17 mg to about 20 mg, or from about 22 mg to about 24 mg, or from about 27 mg to about 29 mg. In some embodiments, the total amount of risperidone, a pharmaceutically acceptable salt of risperidone, or the calcium salt of risperidone in the star-shaped dosage form may be about 14 mg or about 28 mg.

[0216] The inactive arm segment of the dosage form may comprise polycaprolactone (PCL), a radiopaque substance, and an optional colorant. The viscosity of the polycaprolactone used may be from about 1.5 dL / g to about 1.9 dL / g, such as about 1.7 dl / g. The radiopaque substance may be (BiO)2CO3. Any pharmaceutically acceptable colorant may be used. Examples of colorants that may be used include FD&C Blue #5.

[0217] The enteric disintegration matrix of the risperidone dosage form may comprise polycaprolactone (PCL), hypromellose acetate succinate (HPMCAS), poloxamer 407 (P407), and an optional colorant. The viscosity of the polycaprolactone used may be from about 1.5 dL / g to about 1.9 dL / g, such as about 1.7 dL / g. The HPMCAS used may be of the MG grade (M grade: about 7-11% acetyl content, about 10-14% succinyl content, about 21-25% methoxy content, about 5-9% hydroxypropoxy content; G grade: granules). Any pharmaceutically acceptable colorant may be used. Examples of colorants that may be used include iron oxide.

[0218] The time-dependent disintegration matrix of the risperidone dosage form may comprise poly(D,L-lactide-co-glycolide) (PLGA), polyethylene oxide (PEO), and an optional colorant. The poly(D,L-lactide-co-glycolide) may have a lactide:glycolide molar ratio of about 75:25 and a viscosity range of about 0.32 - 0.44 dL / g. The polyethylene oxide used may be from about 60,000 MW to about 125,000 MW, such as from about 90,000 MW to 110,000 MW, or about 100,000 MW.

[0219] The time-dependent disintegration matrix of the risperidone dosage form may comprise polycaprolactone (PCL), poly(D,L-lactide-co-glycolide) (PLGA), polyethylene oxide (PE), and an optional colorant. The PCL may have a viscosity midpoint of about 1.5 dL / g to about 2.1 dL / g; such as 1.7 dL / g, for example Corbion PC17. The poly(D,L-lactide-co-glycolide) may have a lactide:glycolide molar ratio of about 50:50 and a viscosity range of about 0.32 - 0.44 dL / g. The polyethylene oxide used may be from about 60,000 MW to about 125,000 MW, such as from about 90,000 MW to 110,000 MW, or about 100,000 MW.

[0220] The film for regulating the release rate of the risperidone dosage form may comprise polycaprolactone (PCL), copovidone (such as VA64), and magnesium stearate. The viscosity of the polycaprolactone used may be from about 1.5 dL / g to about 1.9 dL / g, such as about 1.7 dL / g.

[0221] The central elastomer of the risperidone dosage form may have a hardness value of about 40A to about 60A, such as a hardness value of about 45A to about 55A, or about 50A. The central elastomer may be made of liquid silicone rubber; for example, the central elastomer may comprise cured liquid silicone rubber.

[0222] Exemplary dosages of the various components of the risperidone dosage forms are provided in the table below. The dosages are given as approximate weight percentages and it should be understood that when ranges are provided, the dosages are selected such that the total amounts to 100%.

[0223]

[0224]

[0225]

[0226]

[0227] Time-dependent disintegration matrix Formulation 1 Formulation 2 Formulation 3 PCL (midpoint viscosity 1.7 dl / g) 40-50 43-47 44.95 PDLG5004A 30-40 33-37 35 PDLG5004 10-25 15-20 18 PEO (100k) 0.5-5 1-3 2 Colorant (optional) 0.005-0.2 0.01-0.1 0.05 (e.g., E172)

[0228] ODMTEP disintegration matrix Formulation 1 Formulation 2 Formulation 3 PCL (e.g., PC17 with midpoint viscosity 1.7 dl / g) 25-35 28-32 30 HPMCAS 60-70 63-67 64.9 Stearic acid 1-5 2-3 2.5 Propylene glycol 1-5 2-3 2.5

[0229]

[0230] The assembled arm may comprise: 1) a first inert segment; 2) a first disintegrating matrix segment; 3) a second inert segment; 4) a second disintegrating matrix segment; 5) a third inert segment; 6) a fourth inert segment; 7) a drug eluting segment, wherein the drug eluting segment comprises a carrier polymer and risperidone or a salt thereof, and wherein the drug eluting segment further comprises a coating comprising a polymer film that modulates the release rate; 8) an optional fifth inert segment; and 9) a third disintegrating matrix segment, which may be arranged in a variety of orders. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(first disintegrating matrix segment)(second inert segment)(second disintegrating matrix segment)(third inert segment)(fourth inert segment)(drug eluting segment)(optional fifth inert segment)(third disintegrating matrix segment). In some embodiments, the fourth inert segment is an inactive spacer. In some embodiments, the first inert segment, the second inert segment, the third inert segment, and the optional fifth inert segment are rPCL spacers. An optional rPCL spacer (inert segment) having a length of about 0.2 - 2 mm, such as a length of about 0.5 mm, may be inserted between any two of the above components, or added to the outer tip of the assembled arm, or between the inner tip of the assembled arm and the elastomeric core.

[0231] Approximate dimensions of the lengths of the segments on the exemplary drug eluting arm are provided below.

[0232] Drug eluting arm

[0233] Component Dimension set 1 Dimension set 2 Dimension set 3 Carrier polymer - active agent segment 1 - 6 mm 2 - 3 mm 2.4 mm Inactive segment (fourth inert segment) 2 - 9 mm 4 - 7 mm 5.6 mm Inert segment (first, second, third, fifth) 0.1 - 2 mm 0.25 - 1 mm 0.5 mm Enteric disintegration matrix 0.5 - 5 mm 1 - 3 mm 1.85 mm Timed disintegration matrix 0.25 - 5 mm 0.5 - 2 mm 1.0 mm Third disintegration matrix 1 - 6 mm 3 - 5 mm 4 mm

[0234] Approximate dimensions of the lengths and thicknesses of the segments on an exemplary drug-eluting arm are provided below.

[0235] Drug-eluting arm

[0236]

[0237] Approximate dimensions of the lengths and thicknesses of the segments on an exemplary drug-eluting arm are provided below.

[0238] Drug-eluting arm

[0239]

[0240]

[0241] The assembled arm can include: 1) a first inert segment; 2) a first disintegrating matrix segment; 3) a second inert segment; 4) a second disintegrating matrix segment; 5) a third inert segment; 6) a fourth inert segment; 7) an optional fifth inert segment; and 8) a third disintegrating matrix segment, and can be arranged in a variety of orders. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(first disintegrating matrix segment)(second inert segment)(second disintegrating matrix segment)(third inert segment)(fourth inert segment)(optional fifth inert segment)(third disintegrating matrix segment). Approximate dimensions of the lengths of the segments on each arm are provided below. An optional rPCL spacer (inert segment) approximately 0.2 - 2 mm in length (e.g., approximately 0.5 mm in length) can be inserted between any two components of the arm, or added to the outer tip of the assembled arm, or between the inner tip of the assembled arm and the elastomeric core. It should be understood that this embodiment of the assembled arm lacks a drug-eluting segment and can be used when it is desired to use one or more non-drug-eluting arms for a risperidone dosage form.

[0242] Approximate dimensions of the lengths of the segments on an exemplary non-drug-eluting arm are provided below:

[0243] Non-drug-eluting arm

[0244] Component Dimension set 1 Dimension set 2 Dimension set 3 Inactive segment (fourth inert segment) 5 - 12 mm 7 - 9 mm 8 mm Inert segments (first, second, third, fifth) 0.1 - 2 mm 0.25 - 1 mm 0.5 mm Enteric disintegration matrix 0.5 - 5 mm 1 - 3 mm 1.85 mm Timed disintegration matrix 0.25 - 5 mm 0.5 - 2 mm 1.0 mm Third disintegration matrix 1 - 6 mm 3 - 5 mm 4 mm

[0245] Approximate dimensions of the lengths and thicknesses of the segments on an exemplary non-drug-eluting arm are provided below: Non-drug-eluting arm

[0246]

[0247] Approximate dimensions of the lengths and thicknesses of the segments on an exemplary non-drug-eluting arm are provided below: Non-drug-eluting arm

[0248]

[0249] Approximate dimensions of the lengths of the segments on an exemplary drug-eluting arm are provided below:

[0250] Drug-eluting arm

[0251] Component Size set 1 Size set 2 Size set 3 Carrier polymer - active agent segment 1 - 6 mm 2 - 3 mm 2.4 mm Inactive segment (fourth inert segment) 5 - 12 mm 7 - 9 mm 8 mm Inert segments (first, second, third, fifth) 0.1 - 2 mm 0.25 - 1 mm 0.5 mm Enteric disintegration matrix 0.5 - 5 mm 1 - 3 mm 1.85 mm Timed disintegration matrix 0.25 - 5 mm 0.5 - 2 mm 1.0 mm Third disintegration matrix 1 - 6 mm 3 - 5 mm 4 mm

[0252] Although the above gastric retention system or dosage form is described as being formulated with risperidone, it is not limited thereto and can be used with other drugs by replacing the segment containing risperidone with a segment containing other drugs and / or replacing the inert segments.

[0253] Exemplary amounts of the various components of the risperidone dosage form are provided in the table below. The amounts are given as approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected so as to total 100%.

[0254]

[0255]

[0256]

[0257] Time - dependent disintegration matrix Formulation 1 Formulation 2 Formulation 3 PCL (viscosity mid - point 1.7 dl / g) 40-50 43-47 44.95 PDLG5004A 30-40 33-37 35 PDLG5004 10-25 15-20 18 PEO (100k) 0.5-5 1-3 2 Colorant (optional) 0.005-0.2 0.01-0.1 0.05 (e.g., E172)

[0258]

[0259]

[0260] The assembled arm can comprise: 1) a first inert segment; 2) a first disintegrating matrix segment; 3) a second inert segment; 4) a second disintegrating matrix segment; 5) a third inert segment; 6) a fourth inert segment; 7) a drug-eluting segment, wherein the drug-eluting segment comprises a carrier polymer and risperidone or a salt thereof, and wherein the drug-eluting segment further comprises a coating comprising a polymer film that modulates the release rate; 8) an optional sixth inert segment; and 9) a fifth inert segment, which can be arranged in a variety of orders. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(first disintegrating matrix segment)(second inert segment)(second disintegrating matrix segment)(third inert segment)(fourth inert segment)(drug-eluting segment)(optional sixth inert segment)(fifth inert segment). In some embodiments, the fourth inert segment is an inactive spacer. In some embodiments, the first, second, third, and optional sixth inert segments are rPCL spacers. In some embodiments, the fifth inert segment is an inactive spacer. An optional rPCL spacer (inert segment) having a length of about 0.2 - 2 mm, such as about 0.5 mm, can be inserted between any two of the above components, or added to the outer tip of the assembled arm, or between the inner tip of the assembled arm and the elastomeric core.

[0261] Approximate dimensions of the lengths of the segments on an exemplary drug-eluting arm are provided below:

[0262] Drug-eluting arm

[0263]

[0264] Approximate dimensions of the lengths and thicknesses of the segments on an exemplary drug-eluting arm are provided below.

[0265] Drug-eluting arm

[0266]

[0267] Approximate dimensions of the lengths and thicknesses of the segments on an exemplary drug-eluting arm are provided below.

[0268] Drug-eluting arm

[0269]

[0270]

[0271] The assembled arm can include: 1) a first inert segment; 2) a first disintegrating matrix segment; 3) a second inert segment; 4) a second disintegrating matrix segment; 5) a third inert segment; 6) a fourth inert segment; 7) an optional sixth inert segment; and 8) a fifth inert segment, and can be arranged in a variety of orders. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(first disintegrating matrix segment)(second inert segment)(second disintegrating matrix segment)(third inert segment)(fourth inert segment)(optional sixth inert segment)(fifth inert segment). Approximate dimensions of the lengths of the segments on each arm are provided below. An optional rPCL spacer (inert segment) having a length of about 0.2 - 2 mm, such as about 0.5 mm, can be inserted between any two of the above components, or added to the outer tip of the assembled arm, or between the inner tip of the assembled arm and the elastomeric core. In some embodiments, the fourth inert segment is an inactive spacer. In some embodiments, the first inert segment, the second inert segment, the third inert segment, and the optional sixth inert segment are rPCL spacers. In some embodiments, the fifth inert segment is an inactive spacer. It should be understood that this embodiment of the assembled arm lacks a drug-eluting segment and can be used when it is desired to use one or more non-drug-eluting arms for a risperidone dosage form.

[0272] Approximate dimensions of the lengths of the segments on an exemplary non-drug-eluting arm are provided below:

[0273] Non-drug-eluting arm

[0274] Component Size set 1 Size set 2 Size set 3 Inactive segment (fourth inert segment) 5 - 12 mm 7 - 9 mm 8 mm Inert segments (first, second, third, sixth) 0.1 - 2 mm 0.25 - 1 mm 0.5 mm Enteric disintegration matrix 0.5 - 5 mm 1 - 3 mm 1.85 mm Timed disintegration matrix 0.25 - 5 mm 0.5 - 2 mm 1.0 mm Inactive segment (fifth inert segment) 1 - 6 mm 3 - 5 mm 4 mm

[0275] The gastric retention system or dosage form described above, although described as being formulated with risperidone, is not limited thereto and can be used with other drugs by replacing the risperidone-containing segment with a segment containing other drugs and / or replacing the inert segment.

[0276] In some embodiments, the star-shaped dosage form for administering risperidone can include arms, which in turn include 1) a carrier polymer-active agent arm segment; 2) an inactive arm segment; 3) one or more enteric linkers; 4) one or more time-dependent linkers; 5) a rate-modulating release film; and / or 6) other optional spacers. The arms are connected to an elastomeric core in a star-shaped device arrangement. Typically, six arms are used for the star-shaped dosage form. In some embodiments, where six arms are used for the star-shaped dosage form, any one of the 1, 2, 3, 4, 5, or 6 arms includes a carrier polymer-active agent arm segment. In some embodiments, where six arms are used for the star-shaped dosage form, 1 arm includes a carrier polymer-active agent arm segment. In some embodiments, where six arms are used for the star-shaped dosage form, 2 arms include a carrier polymer-active agent arm segment. In some embodiments, where six arms are used for the star-shaped dosage form, 3 arms include a carrier polymer-active agent arm segment. In some embodiments, where six arms are used for the star-shaped dosage form, 6 arms include a carrier polymer-active agent arm segment.

[0277] The carrier polymer-active agent arm segment of the risperidone dosage form may comprise risperidone (or a pharmaceutically acceptable salt thereof), polycaprolactone, copovidone (VA64), poloxamer 407 (P407), silica (SiO2), vitamin E succinate (vitE), and optionally a colorant. The calcium salt of risperidone may be used for the carrier polymer-active agent arm. The viscosity of the polycaprolactone used may be about 1.5 dl / g to about 1.9 dl / g, such as about 1.7 dl / g. Any pharmaceutically acceptable colorant may be used. Examples of colorants that may be used include FD&C Red No. 40 aluminum lake, FD&C Yellow No. 5 aluminum lake, or an approximately equal blend of both. In some embodiments, generally, six arms are used for the star-shaped dosage form, and 1, 2, 3, 4, 5, or 6 arms comprise the carrier polymer-active agent arm segment. In some embodiments, 1 arm comprises the carrier polymer-active agent arm segment. In some embodiments, 2 arms comprise the carrier polymer-active agent arm segment. In some embodiments, 3 arms comprise the carrier polymer-active agent arm segment. In some embodiments, 6 arms comprise the carrier polymer-active agent arm segment. In some embodiments, the total amount of active agent contained in the dosage form is 1, 2, 3, 4, 5, or 6 times the amount of active agent contained in a single arm. In some embodiments, the total amount of active agent contained in the dosage form is the same as the amount of active agent contained in a single arm. In some embodiments, the total amount of active agent contained in the dosage form is 3 times the amount of active agent contained in a single arm. In some embodiments, the total amount of active agent contained in the dosage form is 6 times the amount of active agent contained in a single arm. The total weight of risperidone, a pharmaceutically acceptable salt of risperidone, or the calcium salt of risperidone in the star-shaped dosage form may be about 2 mg to about 60 mg, such as about 4 mg to about 50 mg, or about 10 mg to about 20 mg, or about 20 mg to about 30 mg, or about 25 mg to about 35 mg, or about 14 mg to about 18 mg, or about 30 mg to about 34 mg, about 46 mg to about 50 mg, or about 3 mg to about 5 mg, or about 8 mg to about 10 mg, or about 13 mg to about 15 mg, or about 15 mg to about 17 mg, or about 17 mg to about 20 mg, or about 22 mg to about 24 mg, or about 27 mg to about 29 mg, or about 31 mg to about 33 mg, or about 47 mg to about 49 mg. In some embodiments, the total weight of risperidone, a pharmaceutically acceptable salt of risperidone, or the calcium salt of risperidone in the star-shaped dosage form may be about 16 mg, about 32 mg, or about 48 mg.

[0278] The inactive arm segment of the risperidone dosage form may comprise polycaprolactone (PCL), a radiopaque substance, and optionally a colorant. The viscosity of the polycaprolactone used may be from about 1.5 dl / g to about 1.9 dl / g, such as about 1.7 dl / g. The radiopaque substance may be (BiO)2CO3. Any pharmaceutically acceptable colorant may be used. Examples of colorants that may be used include FD&C Blue #5.

[0279] The enteric disintegration matrix of the risperidone dosage form may comprise polycaprolactone (PCL), hypromellose acetate succinate (HPMCAS), and poloxamer 407 (P407). The viscosity of the polycaprolactone used may be from about 1.5 dl / g to about 1.9 dl / g, such as about 1.7 dl / g. The HPMCAS used may be of the MG grade (M grade: about 7 - 11% acetyl content, about 10 - 14% succinyl content, about 21 - 25% methoxy content, about 5 - 9% hydroxypropoxy content; G grade: granular).

[0280] In some embodiments, the filaments surround the gastric retention system in a circumferential direction (e.g., by connecting the distal ends of each arm). The filaments that surround the gastric retention system in a circumferential direction and connect one or more arms of the dosage form may be disintegration filaments. In some embodiments, the filaments comprise poly(lactic - co - glycolic acid) and / or polyglycolic acid.

[0281] The time - dependent disintegration matrix of the risperidone dosage form may comprise polycaprolactone (PCL), poly(D,L - lactide - co - glycolide) (PLGA), poly(ethylene oxide) (PEO), and optionally a colorant. The PCL may have a viscosity mid - point of from about 1.0 dl / g to about 1.4 dl / g; such as 1.2 dl / g, for example Corbion PC12. The poly(D,L - lactide - co - glycolide) may be of a lactide:glycolide molar ratio of about 50:50, with a viscosity range of from about 0.32 - 0.44 dl / g. The poly(ethylene oxide) used may be from about 60,000 MW to about 125,000 MW, such as from about 90,000 MW to 110,000 MW or about 100,000 MW.

[0282] The rate - modulating release film of the risperidone dosage form may comprise polycaprolactone (PCL), copovidone (such as VA64), and magnesium stearate. The polycaprolactone used may have a viscosity of from about 1.5 dL / g to about 1.9 dL / g, such as about 1.7 dL / g.

[0283] The central elastomer of the risperidone dosage form may have a hardness value of from about 40A to about 60A, such as a hardness value of from about 45A to about 55A, or a hardness value of about 50A. The central elastomer may be made of liquid silicone rubber; for example, the central elastomer may comprise cured liquid silicone rubber.

[0284] In one embodiment, exemplary amounts of the various components for a risperidone dosage form are provided in the table below. The amounts are given as approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected such that the total is 100%.

[0285]

[0286]

[0287]

[0288] Enteric disintegration matrix (E - DM3) Formulation 1 Formulation 2 Formulation 3 PCL (e.g., PC17 with viscosity mid - point 1.7 dl / g) 30-40 32-37 34 HPMCAS 60-70 62-66 64 P407 0.5-5 1-3 2

[0289] Time - dependent disintegration matrix Formulation 1 Formulation 2 Formulation 3 PCL (viscosity mid - point 1.2 dl / g) 40-50 43-47 44.95 PDLG5004A 30-40 33-37 35 PDLG5004 10-25 15-20 18 PEO (100k) 0.5-5 1-3 2 Colorant (optional) 0.005-0.2 0.01-0.1 0.05 (e.g., E172)

[0290] Film for regulating release rate Formulation 1 Formulation 2 Formulation 3 PCL (e.g., PC17 with viscosity mid - point 1.7 dl / g) 67-77 71-76 73.5 VA64 20-30 22-27 24.5 Magnesium stearate 0.5-5 1-3 2.0

[0291] In one embodiment, exemplary amounts of the various components for a risperidone dosage form are provided in the table below. The amounts are given as approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected such that the total is 100%.

[0292]

[0293]

[0294]

[0295] Enteric disintegration matrix Formulation 1 Formulation 2 Formulation 3 PCL (e.g., PC17 with viscosity mid - point 1.7 dl / g) 30-40 32-37 34 HPMCAS 60-70 62-66 64 P407 0.5-5 1-3 2

[0296]

[0297]

[0298] In one embodiment, exemplary amounts of the various components for a risperidone dosage form are provided in the table below. The amounts are given as approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected such that the total is 100%.

[0299]

[0300]

[0301]

[0302] Time - dependent disintegration matrix Formulation 1 Formulation 2 Formulation 3 PCL (viscosity mid - point 1.2 dl / g) 45-55 48-52 49.95 PDLG5004A 33-43 36-40 38 PDLG5004 5-15 8-12 10 PEO (100k) 0.5-5 1-3 2 Colorant (optional) 0.005-0.2 0.01-0.1 0.05 (e.g., E172)

[0303] Film for regulating release rate Formulation 1 Formulation 2 Formulation 3 PCL (e.g., PC17 with viscosity mid - point 1.7 dl / g) 67-77 71-76 73.5 VA64 20-30 22-27 24.5 Magnesium stearate 0.5-5 1-3 2.0

[0304] In one embodiment, exemplary amounts of the various components for a risperidone dosage form are provided in the following table. The amounts are given as approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected such that they total 100%.

[0305]

[0306]

[0307]

[0308] Enteric disintegration matrix Formulation 1 Formulation 2 Formulation 3 PCL (e.g., PC17, viscosity mid - point 1.7 dl / g) 30-40 32-37 34 HPMCAS 60-70 62-66 64 P407 0.5-5 1-3 2

[0309]

[0310]

[0311] In one embodiment, exemplary amounts of the various components for a risperidone dosage form are provided in the following table. The amounts are given as approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected such that they total 100%.

[0312]

[0313]

[0314]

[0315] Time - dependent disintegration matrix Formulation 1 Formulation 2 Formulation 3 PCL (viscosity mid - point 1.2 dl / g) 45-55 48-52 49.95 PDLG5004A 27-37 30-34 31.75 PDLG5004 10-22 14-18 15.75 PEO (100k) 0.5-5 1.5-3.5 2.5 Colorant (optional) 0.005-0.2 0.01-0.1 0.05 (e.g., E172)

[0316] Film for regulating release rate Formulation 1 Formulation 2 Formulation 3 PCL (e.g., PC17 with viscosity midpoint of 1.7 dl / g) 67-77 71-76 73.5 VA64 20-30 22-27 24.5 Magnesium stearate 0.5-5 1-3 2.0

[0317] The assembled arm can comprise: 1) a first disintegration matrix; 2) a first inert segment; 3) a second disintegration matrix; 4) a second inert segment; 5) a drug eluting segment, wherein the drug eluting segment comprises a carrier polymer and risperidone or a salt thereof, and wherein the drug eluting segment further comprises a coating comprising a polymer film that modulates the release rate; and 6) a third inert segment, which can be arranged in a variety of sequences. One such sequence is, starting from the proximal end attached to the central elastomer and proceeding distally: (first disintegration matrix)(first inert segment)(second disintegration matrix)(second inert segment)(drug eluting segment)(third inert segment). In some embodiments, the third inert segment is an inactive spacer. In some embodiments, the first inert segment and the second inert segment are rPCL spacers. Optionally, rPCL spacers (inert segments) of about 0.2 - 2 mm in length, such as about 0.5 mm in length, can be inserted between any two of the above components, or added to the outer tip of the assembled arm, or between the inner tip of the assembled arm and the elastomeric core.

[0318] Approximate dimensions of the lengths of the segments on an exemplary drug-eluting arm are provided below:

[0319] Drug-eluting arm

[0320]

[0321] Approximate dimensions of the lengths and thicknesses of the segments on an exemplary drug-eluting arm are provided below.

[0322] Drug-eluting arm

[0323]

[0324] Approximate dimensions of the lengths and thicknesses of the segments on an exemplary drug-eluting arm are provided below.

[0325] Drug-eluting arm

[0326]

[0327] The assembled arm can include 1) a first disintegrating matrix; 2) a first inert segment; 3) a second disintegrating matrix; 4) a second inert segment; and 5) a third inert segment, which can be arranged in a variety of orders. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first disintegrating matrix)(first inert segment)(second disintegrating matrix)(second inert segment)(third inert segment). An optional rPCL spacer (inert segment) having a length of about 0.2 - 2 mm, such as about 0.5 mm, can be inserted between any two of the following components, or added to the outer tip of the assembled arm, or between the inner tip of the assembled arm and the elastomeric core. In some embodiments, the third inert segment is an inactive spacer. It should be understood that this embodiment of the assembled arm lacks a drug-eluting segment and can be used when it is desired to use one or more non-drug-eluting arms for a risperidone dosage form.

[0328] Approximate dimensions of the lengths of the segments on an exemplary non-drug-eluting arm are provided below:

[0329] Non-drug-eluting arm

[0330]

[0331] Approximate dimensions of the lengths and thicknesses of the segments on an exemplary non-drug-eluting arm are provided below.

[0332] Non-drug-eluting arm

[0333]

[0334] Approximate dimensions of the lengths and thicknesses of the segments on an exemplary non-drug-eluting arm are provided below.

[0335] Non-drug eluting arm

[0336]

[0337]

[0338] The above gastric retention system or dosage form, although described as formulated with risperidone, is not limited thereto and can be used with other drugs by replacing the segment containing risperidone with a segment containing other drugs and / or replacing the inert segment with other drugs.

[0339] Exemplary gastric retention system

[0340] The following gastric retention systems are exemplary to better illustrate certain embodiments of the systems described herein. Since these examples are merely exemplary, they are not intended to limit the gastric retention systems described herein. Given the disclosure provided, those skilled in the art can contemplate additional configurations of gastric retention systems. Any gastric retention system shown herein as formulated with risperidone is not limited thereto and can be used with other drugs by replacing the segment containing risperidone with a segment containing other drugs and / or replacing the inert segment. Any of the gastric retention systems disclosed herein can be used as the gastric retention system for administration to an individual in the methods disclosed herein.

[0341] In some embodiments, the gastric retention system comprises at least one arm that includes a drug eluting segment, wherein the arm comprises: (a) a first inert segment as described in any embodiment of the inert segments above, (b) a timed disintegrating matrix as described in any embodiment above, (c) a second inert segment as described in any embodiment of the inert segments above, (d) an enteric disintegrating matrix as described in any embodiment above, (e) a third inert segment as described in any embodiment of the inert segments above, (f) a drug eluting segment as described in any embodiment above, (g) a fourth inert segment as described in any embodiment of the inert segments above, and (h) a third disintegrating matrix as described in any embodiment above. The first inert segment can be attached to the central elastomer.

[0342] In some embodiments, the gastric retention system comprises at least one arm that includes a drug eluting segment, wherein the arm comprises: (a) a first inert segment as described in any of the embodiments of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), (b) a timed disintegrating matrix as described in any of the embodiments above (e.g., any one of T-DM1, T-DM2, T-DM3, T-DM4, T-DM5, T-DM6), (c) a second inert segment as described in any of the embodiments of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), (d) an enteric disintegrating matrix as described in any of the embodiments above (e.g., E-DM1 or E-DM2), (e) a third inert segment as described in any of the embodiments of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), (f) a drug eluting segment as described in any of the embodiments above (e.g., CP-1), (g) a fourth inert segment as described in any of the embodiments of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), and (h) a third disintegrating matrix as described in any of the embodiments above (e.g., ODMTEP). The drug eluting arm may comprise an optional fifth inert segment as described in any of the embodiments of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3). The segments may be arranged in any order. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(timed disintegrating matrix)(second inert segment)(enteric disintegrating matrix)(third inert segment)(fourth inert segment)(drug eluting segment)(third disintegrating matrix segment). Another such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(timed disintegrating matrix)(second inert segment)(enteric disintegrating matrix)(third inert segment)(fourth inert segment)(drug eluting segment)(fifth inert segment)(third disintegrating matrix segment). The first inert segment may be attached to the central elastomer.

[0343] In some embodiments, the gastric retention system comprises at least one arm that includes a drug eluting segment, wherein the arm may be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment, (b) a timed disintegrating matrix, (c) a second inert segment, (d) an enteric disintegrating matrix, (e) a third inert segment, (f) a drug eluting segment, (g) a fourth inert segment, and (h) a third disintegrating matrix, wherein:

[0344] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 40 - about 65 durometer;

[0345] (a) The first inert segment contains about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0346] (b) The timed disintegration matrix contains about 40 wt% - about 50 wt% of PCL, about 30 wt% - about 40 wt% of an acid - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) with a viscosity mid - point of about 0.4 dl / g, about 10 wt% - about 25 wt% of a copolymer of DL - lactide and glycolide (50 / 50 molar ratio) with a viscosity mid - point of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color - absorbing dye E172;

[0347] (c) The second inert segment contains about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0348] (d) The enteric - disintegration matrix contains about 59 wt% - about 69 wt% of HPMCAS, about 29 wt% - about 39 wt% of PCL, about 0.5 wt% - about 5 wt% of poloxamer (such as P407), and optionally about 0.01 wt% - about 0.2 wt% of iron oxide (such as E172);

[0349] (e) The third inert segment contains about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0350] (f) The drug - eluting segment contains about 30 wt% - about 40 wt% of risperidone, about 51 wt% - about 61 wt% of PCL, about 2 wt% - about 8 wt% of VA64, about 1 wt% - about 5 wt% of P407, about 0.1 wt% - about 1 wt% of vitamin E succinate, about 0.1 wt% - about 1 wt% of SiO2, and about 0.01 wt% - about 0.5 wt% of a pigment;

[0351] (g) The fourth inert segment contains about 61 wt% - about 71 wt% of PCL, about 27 wt% - about 37 wt% of copovidone, about 0.2 wt% - about 4 wt% of poloxamer, and optionally about 0.005 wt% - about 0.2 wt% of a color - absorbing dye FD&C blue #1; and / or

[0352] (h) The third disintegration matrix contains about 60 wt% - about 70 wt% of HPMCAS, about 25 wt% - about 35 wt% of PCL, about 1 wt% - about 5 wt% of propylene glycol, about 1 wt% - about 5 wt% of stearic acid, and optionally about 0.01 wt% - about 0.5 wt% of iron oxide.

[0353] In some embodiments, the gastric retention system comprises at least one arm, the arm comprising a drug eluting segment, wherein the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment, (b) a time-dependent disintegrating matrix, (c) a second inert segment, (d) an enteric disintegrating matrix, (e) a third inert segment, (f) a drug eluting segment, (g) a fourth inert segment, and (h) a third disintegrating matrix, wherein:

[0354] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 45 - about 55 Shore hardness;

[0355] (a) The first inert segment comprises about 68 wt% - about 72 wt% PCL and about 28 wt% - about 32 wt% (BiO)2CO3;

[0356] (b) The time-dependent disintegrating matrix comprises about 43 wt% - about 47 wt% PCL, about 33 wt% - about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 15 wt% - about 20 wt% of a copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 1 wt% - about 3 wt% polyethylene glycol 100k, and about 0.01 wt% - about 0.1 wt% of a color-absorbing dye E172;

[0357] (c) The second inert segment comprises about 68 wt% - about 72 wt% PCL and about 28 wt% - about 32 wt% (BiO)2CO3;

[0358] (d) The enteric disintegrating matrix comprises about 62 wt% - about 66 wt% HPMCAS, about 32 wt% - about 36 wt% PCL, about 1 wt% - about 3 wt% poloxamer (e.g., P407), and optionally about 0.05 wt% - about 0.15 wt% iron oxide (e.g., E172);

[0359] (e) The third inert segment comprises about 68 wt% - about 72 wt% PCL and about 28 wt% - about 32 wt% (BiO)2CO3;

[0360] (f) The drug eluting segment comprises about 33 wt% - about 37 wt% risperidone, about 54 wt% - about 58 wt% PCL, about 4 wt% - about 6 wt% VA64, about 2 wt% - about 4 wt% P407, about 0.2 wt% - about 0.8 wt% vitamin E succinate, about 0.2 wt% - about 0.8 wt% SiO2, and about 0.05 wt% - about 0.15 wt% pigment;

[0361] (g) The fourth inert segment comprises from about 64 wt% to about 69 wt% of PCL, from about 30 wt% to about 34 wt% of copovidone, from about 0.5 wt% to about 2.5 wt% of poloxamer, and optionally from about 0.01 wt% to about 0.1 wt% of the color-absorbing dye FD&C Blue #1; and / or

[0362] (h) The third disintegration matrix comprises from about 63 wt% to about 67 wt% of HPMCAS, from about 28 wt% to about 32 wt% of PCL, from about 2 wt% to about 3 wt% of propylene glycol, from about 2 wt% to about 3 wt% of stearic acid, and optionally from about 0.05 wt% to about 0.15 wt% of iron oxide.

[0363] In some embodiments, the gastric retention system comprises at least one arm that includes a drug eluting segment, wherein the arm may be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment, (b) a time-dependent disintegration matrix, (c) a second inert segment, (d) an enteric disintegration matrix, (e) a third inert segment, (f) a drug eluting segment, (g) a fourth inert segment, and (h) a third disintegration matrix, wherein:

[0364] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 50 Shore value;

[0365] (a) The first inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3;

[0366] (b) The time-dependent disintegration matrix comprises about 44.95 wt% of PCL, about 35 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 18 wt% of a copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% of polyethylene glycol 100k, and from about 0.005 wt% to about 0.2 wt%, such as about 0.05%, of the color-absorbing dye E172;

[0367] (c) The second inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3;

[0368] (d) The enteric disintegration matrix comprises about 63.95 wt% of HPMCAS, about 33.95 wt% of PCL, about 2 wt% of poloxamer (such as P407), and about 0.1 wt% of iron oxide (such as E172);

[0369] (e) The third inert segment comprises approximately 70 wt% of PCL and approximately 30 wt% of (BiO)2CO3;

[0370] (f) The drug eluting segment comprises approximately 35.0 wt% of risperidone, approximately 55.9 wt% of PCL, approximately 5.0 wt% of VA64, approximately 3.0 wt% of P407, approximately 0.5 wt% of vitamin E succinate, approximately 0.5 wt% of SiO2 and approximately 0.1 wt% of pigment;

[0371] (g) The fourth inert segment comprises approximately 66.45 wt% of PCL, approximately 32 wt% of copovidone, approximately 1.5 wt% of poloxamer and optionally approximately 0.05 wt% of FD&C Blue #1, an absorbent color dye; and / or

[0372] (h) The third disintegration matrix comprises 64.9 wt% of HPMCAS, approximately 30 wt% of PCL, approximately 2.5 wt% of propylene glycol and approximately 2.5 wt% of stearic acid and optionally approximately 0.1 wt% of iron oxide, such as approximately 0.025% of magnetite and approximately 0.075% of FD&C Red 40.

[0373] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, where the arm may be attached to a central elastomer and the arm may comprise one or more of the following: (a) a first inert segment as described in any embodiment of the inert segments above, (b) a timed disintegration matrix as described in any embodiment above, (c) a second inert segment as described in any embodiment of the inert segments above, (d) an enteric disintegration matrix as described in any embodiment above, (e) a third inert segment as described in any embodiment of the inert segments above, (f) a drug-free segment as described in any embodiment above, (g) a fourth inert segment as described in any embodiment of the inert segments above, and (h) a third disintegration matrix as described in any embodiment above.

[0374] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, where the drug-free arm may be attached to a central elastomer and the arm may comprise one or more of the following: (a) a first inert segment as described in any embodiment of the inert segments above, (b) a timed disintegration matrix as described in any embodiment above, (c) a second inert segment as described in any embodiment of the inert segments above, (d) an enteric disintegration matrix as described in any embodiment above, (e) a third inert segment as described in any embodiment of the inert segments above, (f) a fourth inert segment as described in any embodiment of the inert segments above, and (g) a third disintegration matrix as described in any embodiment above.

[0375] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, where the drug-free arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment as described in any of the embodiments of the inert segments above (e.g., any of IS-1, IS-2, or IS-3), (b) a timed disintegration matrix as described in any of the embodiments above (e.g., any of T-DM1, T-DM2, T-DM3, T-DM4, T-DM5, T-DM6), (c) a second inert segment as described in any of the embodiments of the inert segments above (e.g., any of IS-1, IS-2, or IS-3), (d) an enteric disintegration matrix as described in any of the embodiments above (e.g., E-DM1 or E-DM2), (e) a third inert segment as described in any of the embodiments of the inert segments above (e.g., any of IS-1, IS-2, or IS-3), (f) a fourth inert segment as described in any of the embodiments of the inert segments above (e.g., any of IS-1, IS-2, or IS-3), and (g) a third disintegration matrix as described in any of the embodiments above (e.g., ODMTEP). The drug-free arm can optionally comprise a fifth inert segment as described in any of the embodiments of the inert segments above (e.g., any of IS-1, IS-2, or IS-3). The segments can be arranged in any order. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(timed disintegration matrix)(second inert segment)(enteric disintegration matrix)(third inert segment)(fourth inert segment)(third disintegration matrix segment). Another such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(timed disintegration matrix)(second inert segment)(enteric disintegration matrix)(third inert segment)(fourth inert segment)(fifth inert segment)(third disintegration matrix segment). The first inert segment can be attached to the central elastomer.

[0376] In some embodiments that can be combined with any of the embodiments herein, a filament circumferentially surrounds the gastric retention system (e.g., by connecting the distal ends of each arm). The filament that circumferentially surrounds the gastric retention system and connects one or more arms of the risperidone dosage form can be a non-disintegrating filament. In some embodiments, the filament comprises thermoplastic polyurethane. In some embodiments, the filament comprises methylene bis(4-phenyl isocyanate), poly(tetramethylene oxide), and / or 1,4-butanediol.

[0377] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, where the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment, (b) a timed disintegration matrix, (c) a second inert segment, (d) an enteric disintegration matrix, (e) a third inert segment, (f) a fourth inert segment, and (g) a third disintegration matrix, where:

[0378] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 40 - about 65 shore hardness value;

[0379] (a) The first inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0380] (b) The timed disintegration matrix comprises about 40 wt% - about 50 wt% of PCL, about 30 wt% - about 40 wt% of an acid - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 10 wt% - about 25 wt% of a copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of an absorption color dye E172;

[0381] (c) The second inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0382] (d) The enteric disintegration matrix comprises about 59 wt% - about 69 wt% of HPMCAS, about 29 wt% - about 39 wt% of PCL, about 0.5 wt% - about 5 wt% of poloxamer (e.g., P407), and optionally about 0.01 wt% - about 0.2 wt% of iron oxide (e.g., E172);

[0383] (e) The third inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0384] (f) The fourth inert segment comprises about 61 wt% - about 71 wt% of PCL, about 27 wt% - about 37 wt% of copovidone, about 0.2 wt% - about 4 wt% of poloxamer, and optionally about 0.005 wt% - about 0.2 wt% of an absorption color dye FD&C blue #1; and / or

[0385] (g) The third disintegration matrix comprises about 60 wt% - about 70 wt% of HPMCAS, about 25 wt% - about 35 wt% of PCL, about 1 wt% - about 5 wt% of propylene glycol, about 1 wt% - about 5 wt% of stearic acid, and optionally about 0.01 wt% - about 0.5 wt% of iron oxide.

[0386] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, wherein the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment, (b) a time-dependent disintegration matrix, (c) a second inert segment, (d) an enteric disintegration matrix, (e) a third inert segment, (f) a fourth inert segment, and (g) a third disintegration matrix, wherein:

[0387] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 45 - about 55 Shore hardness;

[0388] (a) The first inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3;

[0389] (b) The time-dependent disintegration matrix comprises about 43 wt% - about 47 wt% of PCL, about 33 wt% - about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 15 wt% - about 20 wt% of a copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 1 wt% - about 3 wt% of polyethylene glycol 100k, and about 0.01 wt% - about 0.1 wt% of an absorption color dye E172;

[0390] (c) The second inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3;

[0391] (d) The enteric disintegration matrix comprises about 62 wt% - about 66 wt% of HPMCAS, about 32 wt% - about 36 wt% of PCL, about 1 wt% - about 3 wt% of poloxamer (e.g., P407), and optionally about 0.05 wt% - about 0.15 wt% of iron oxide (e.g., E172);

[0392] (e) The third inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3;

[0393] (f) The fourth inert segment comprises from about 64 wt% to about 69 wt% of PCL, from about 30 wt% to about 34 wt% of copovidone, from about 0.5 wt% to about 2.5 wt% of poloxamer, and optionally from about 0.01 wt% to about 0.1 wt% of the color-absorbing dye FD&C Blue #1; and / or

[0394] (g) The third disintegration matrix comprises from about 63 wt% to about 67 wt% of HPMCAS, from about 28 wt% to about 32 wt% of PCL, from about 2 wt% to about 3 wt% of propylene glycol, from about 2 wt% to about 3 wt% of stearic acid, and optionally from about 0.05 wt% to about 0.15 wt% of iron oxide.

[0395] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, where the arm can be attached to a central elastomer, and the arm comprises one or more of: (a) a first inert segment, (b) a timed disintegration matrix, (c) a second inert segment, (d) an enteric disintegration matrix, (e) a third inert segment, (f) a fourth inert segment, and (g) a third disintegration matrix, where:

[0396] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 50 Shore value;

[0397] (a) The first inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3;

[0398] (b) The time-dependent disintegration matrix comprises about 44.95 wt% of PCL, about 35 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 18 wt% of a copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% of polyethylene glycol 100k, and about 0.05 wt% of the color-absorbing dye E172;

[0399] (c) The second inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3;

[0400] (d) The enteric disintegration matrix comprises about 63.95 wt% of HPMCAS, about 33.95 wt% of PCL, about 2 wt% of poloxamer (such as P407), and about 0.1 wt% of iron oxide (such as E172);

[0401] (e) The third inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3;

[0402] (f) The fourth inert segment comprises about 66.45 wt% of PCL, about 32 wt% of copovidone, about 1.5 wt% of poloxamer, and optionally about 0.05 wt% of the color-absorbing dye FD&C Blue #1; and / or

[0403] (g) The third disintegration matrix comprises 64.9 wt% of HPMCAS, about 30 wt% of PCL, about 2.5 wt% of propylene glycol, and about 2.5 wt% of stearic acid, and optionally about 0.1 wt% of iron oxide, such as about 0.025% of magnetite and about 0.075% of FD&C Red 40.

[0404] In some embodiments of any of the gastric retention systems described herein, the gastric retention system comprises at least one arm that includes a drug eluting segment, wherein the arm further comprises a fifth optional inert segment, wherein the fifth optional inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3. In some embodiments, the fifth optional inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3. In some embodiments, the fifth optional inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3.

[0405] In any of the above embodiments, the arm can be attached to a central elastomer on the first inert segment. That is, the first inert segment is the proximal end of the arm.

[0406] The following table provides a list of the lengths of each segment of the gastric retention system. Each of the following ranges or values can be considered the indicated "approximate" range or value, or exactly the indicated range or value.

[0407] Segment Length Drug eluting segment 2.4 mm Fourth inert segment 8 mm First, second, third or fifth inert segment 0.5 mm Enteric disintegration matrix 1.85 mm Time-dependent disintegration matrix 1.00 mm Third disintegration matrix 4 mm

[0408] For further embodiments, the following table provides a list of the lengths of each segment in the drug eluting arm of the gastric retention system. Each of the following ranges or values can be considered the indicated "approximate" range or value, or exactly the indicated range or value.

[0409] Segment Length Drug eluting segment 2.4 mm Fourth inert segment 5.6 mm First, second, third or fifth inert segment 0.5 mm Enteric disintegration matrix 1.85 mm Time-dependent disintegration matrix 1.00 mm Third disintegration matrix 4 mm

[0410] The above gastric retention system, although described as formulated with risperidone, is not limited thereto and can be used with other drugs by replacing the segment containing risperidone and / or replacing the inert segment with segments containing other drugs.

[0411] The following gastric retention systems are exemplary to better illustrate certain embodiments of the systems described herein.

[0412] In some embodiments, the gastric retention system comprises at least one arm, the arm comprising a drug eluting segment, wherein the arm comprises: (a) a first inert segment as described in any embodiment of the inert segments above, (b) a timed disintegrating matrix as described in any of the embodiments above, (c) a second inert segment as described in any embodiment of the inert segments above, (d) an enteric disintegrating matrix as described in any of the embodiments above, (e) a third inert segment as described in any embodiment of the inert segments above, (f) a fourth inert segment as described in any embodiment of the inert segments above, (g) a drug eluting segment as described in any of the embodiments above, and (h) a fifth inert segment as described in any of the embodiments above. The first inert segment may be attached to a central elastomer.

[0413] In some embodiments, the gastric retention system comprises at least one arm, the arm comprising a drug eluting segment, wherein the arm comprises: (a) a first inert segment as described in any embodiment of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), (b) a timed disintegrating matrix as described in any of the embodiments above (e.g., any one of T-DM1, T-DM2, T-DM3, T-DM4, T-DM5, T-DM6), (c) a second inert segment as described in any embodiment of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), (d) an enteric disintegrating matrix as described in any of the embodiments above (e.g., E-DM1 or E-DM2), (e) a third inert segment as described in any embodiment of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), (f) a fourth inert segment as described in any embodiment of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), (g) a drug eluting segment as described in any of the embodiments above, and (h) a fifth inert segment as described in any of the embodiments above (e.g., any one of IS-1, IS-2, or IS-3). The drug eluting arm may optionally comprise a sixth inert segment as described in any embodiment of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3). The segments may be arranged in a variety of orders. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(timed disintegrating matrix)(second inert segment)(enteric disintegrating matrix)(third inert segment)(fourth inert segment)(drug eluting segment)(fifth inert segment). One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(timed disintegrating matrix)(second inert segment)(enteric disintegrating matrix)(third inert segment)(fourth inert segment)(drug eluting segment)(optional sixth inert segment)(fifth inert segment). The first inert segment may be attached to a central elastomer.

[0414] In some embodiments, the gastric retention system comprises at least one arm, the arm comprising a drug eluting segment, wherein the arm may be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment, (b) a timed disintegration matrix, (c) a second inert segment, (d) an enteric disintegration matrix, (e) a third inert segment, (f) a fourth inert segment, (g) a drug eluting segment, and (h) a fifth inert segment, wherein:

[0415] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 40 - about 65 shore hardness value;

[0416] (a) The first inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0417] (b) The timed disintegration matrix comprises about 40 wt% - about 50 wt% of PCL, about 30 wt% - about 40 wt% of an acid - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 10 wt% - about 25 wt% of an ester - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of an absorption color dye E172;

[0418] (c) The second inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0419] (d) The enteric disintegration matrix comprises about 59 wt% - about 69 wt% of HPMCAS, about 29 wt% - about 39 wt% of PCL, about 0.5 wt% - about 5 wt% of poloxamer (e.g., P407), and optionally about 0.01 wt% - about 0.2 wt% of iron oxide (e.g., E172);

[0420] (e) The third inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0421] (f) The fourth inert segment comprises about 61 wt% - about 71 wt% of PCL, about 27 wt% - about 37 wt% of copovidone, about 0.2 wt% - about 4 wt% of poloxamer, and optionally about 0.005 wt% - about 0.2 wt% of an absorption color dye FD&C blue #1;

[0422] (g) The drug eluting segment contains about 30 wt% - about 40 wt% of risperidone, about 51 wt% - about 61 wt% of PCL, about 2 wt% - about 8 wt% of VA64, about 1 wt% - about 5 wt% of P407, about 0.1 wt% - about 1 wt% of vitamin E succinate, about 0.1 wt% - about 1 wt% of SiO2, and about 0.01 wt% - about 0.5 wt% of pigment; and / or

[0423] (h) The fifth inert segment contains about 35 wt% - about 45 wt% of PCL, about 37 wt% - about 47 wt% of copovidone, about 10 wt% - about 20 wt% of polyethylene glycol, about 1 wt% - about 5 wt% of poloxamer, and optionally about 0.0005 wt% - about 0.02 wt% of the color absorbing dye E172.

[0424] In some embodiments, the gastric retention system comprises at least one arm that includes a drug eluting segment, where the arm can be attached to a central elastomer and the arm comprises one or more of the following: (a) a first inert segment, (b) a time-dependent disintegrating matrix, (c) a second inert segment, (d) an enteric disintegrating matrix, (e) a third inert segment, (f) a fourth inert segment, (g) a drug eluting segment, and (h) a fifth inert segment, wherein:

[0425] The central elastomer comprises liquid silicone rubber (LSR) having a hardness with a hardness value of about 45 - about 55;

[0426] (a) The first inert segment contains about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3;

[0427] (b) The time-dependent disintegrating matrix contains about 43 wt% - about 47 wt% of PCL, about 33 wt% - about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 15 wt% - about 20 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 1 wt% - about 3 wt% of polyethylene glycol 100k, and about 0.01 wt% - about 0.1 wt% of the color absorbing dye E172;

[0428] (c) The second inert segment contains about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3;

[0429] (d) The enteric disintegration matrix comprises about 62 wt% - about 66 wt% of HPMCAS, about 32 wt% - about 36 wt% of PCL, about 1 wt% - about 3 wt% of poloxamer (e.g., P407), and optionally about 0.05 wt% - about 0.15 wt% of iron oxide (e.g., E172);

[0430] (e) The third inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3;

[0431] (f) The fourth inert segment comprises about 64 wt% - about 69 wt% of PCL, about 30 wt% - about 34 wt% of copovidone, about 0.5 wt% - about 2.5 wt% of poloxamer, and optionally about 0.01 wt% - about 0.1 wt% of the color-absorbing dye FD&C Blue #1;

[0432] (g) The drug eluting segment comprises about 33 wt% - about 37 wt% of risperidone, about 54 wt% - about 58 wt% of PCL, about 4 wt% - about 6 wt% of VA64, about 2 wt% - about 4 wt% of P407, about 0.2 wt% - about 0.8 wt% of vitamin E succinate, about 0.2 wt% - about 0.8 wt% of SiO2, and about 0.05 wt% - about 0.15 wt% of pigment; and / or

[0433] (h) The fifth inert segment comprises about 38 wt% - about 42 wt% of PCL, about 40 wt% - about 44 wt% of copovidone, about 13 wt% - about 17 wt% of polyethylene glycol, about 2 wt% - about 4 wt% of poloxamer, and optionally about 0.001 wt% - about 0.01 wt% of the color-absorbing dye E172.

[0434] In some embodiments, the gastric retention system comprises at least one arm, the arm comprising a drug eluting segment, wherein the arm may be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment, (b) a timed disintegration matrix, (c) a second inert segment, (d) an enteric disintegration matrix, (e) a third inert segment, (f) a fourth inert segment, (g) a drug eluting segment, and (h) a fifth inert segment, wherein:

[0435] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 50 durometer;

[0436] (a) The first inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3;

[0437] (b) Time-dependent disintegration matrix, the time-dependent disintegration matrix comprising about 44.95 wt% PCL, about 35 wt% acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 18 wt% ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% polyethylene glycol 100k and about 0.005 wt% - about 0.2 wt%, such as about 0.05% of the color-absorbing dye E172;

[0438] (c) The second inert segment comprises about 70 wt% PCL and about 30 wt% (BiO)2CO3;

[0439] (d) Enteric disintegration matrix comprising about 63.95 wt% HPMCAS, about 33.95 wt% PCL, about 2 wt% poloxamer (such as P407) and about 0.1 wt% iron oxide (such as E172);

[0440] (e) The third inert segment comprises about 70 wt% PCL and about 30 wt% (BiO)2CO3;

[0441] (f) The fourth inert segment comprises about 66.45 wt% PCL, about 32 wt% copovidone, about 1.5 wt% poloxamer and optionally about 0.05 wt% of the color-absorbing dye FD&C Blue #1;

[0442] (g) Drug eluting segment comprising about 35.0 wt% risperidone, about 55.9 wt% PCL, about 5.0 wt% VA64, about 3.0 wt% P407, about 0.5 wt% vitamin E succinate, about 0.5 wt% SiO2 and about 0.1 wt% pigment; and / or

[0443] (h) The fifth inert segment comprises about 39.995 wt% PCL, about 42 wt% copovidone, about 15 wt% polyethylene glycol, about 3 wt% poloxamer and optionally about 0.05 wt% of the color-absorbing dye E172.

[0444] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, wherein the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment as described in any of the embodiments of the inert segments above, (b) a timed disintegrating matrix as described in any of the embodiments above, (c) a second inert segment as described in any of the embodiments of the inert segments above, (d) an enteric disintegrating matrix as described in any of the embodiments above, (e) a third inert segment as described in any of the embodiments of the inert segments above, (f) a fourth inert segment as described in any of the embodiments of the inert segments above, and (g) a fifth inert segment as described in any of the embodiments above.

[0445] In some embodiments, the gastric retention system comprises at least one arm that does not contain a drug eluting segment, wherein the arm comprises: (a) a first inert segment as described in any of the embodiments of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), (b) a timed disintegrating matrix as described in any of the embodiments above (e.g., any one of T-DM1, T-DM2, T-DM3, T-DM4, T-DM5, T-DM6), (c) a second inert segment as described in any of the embodiments of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), (d) an enteric disintegrating matrix as described in any of the embodiments above (e.g., E-DM1 or E-DM2), (e) a third inert segment as described in any of the embodiments of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), (f) a fourth inert segment as described in any of the embodiments of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3), and (g) a fifth inert segment as described in any of the embodiments above (e.g., any one of IS-1, IS-2, or IS-3). The drug-free arm can optionally comprise a sixth inert segment as described in any of the embodiments of the inert segments above (e.g., any one of IS-1, IS-2, or IS-3). The segments can be arranged in a variety of orders. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(timed disintegrating matrix)(second inert segment)(enteric disintegrating matrix)(third inert segment)(fourth inert segment)(fifth inert segment). One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (first inert segment)(timed disintegrating matrix)(second inert segment)(enteric disintegrating matrix)(third inert segment)(fourth inert segment)(optional sixth inert segment)(fifth inert segment). The first inert segment can be attached to the central elastomer.

[0446] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, where the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment, (b) a timed disintegration matrix, (c) a second inert segment, (d) an enteric disintegration matrix, (e) a third inert segment, (f) a fourth inert segment, and (g) a fifth inert segment, where:

[0447] The central elastomer comprises liquid silicone rubber (LSR) having a hardness value of about 40 - about 65;

[0448] (a) The first inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0449] (b) The timed disintegration matrix comprises about 40 wt% - about 50 wt% of PCL, about 30 wt% - about 40 wt% of an acid - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 10 wt% - about 25 wt% of an ester - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color - absorbing dye E172;

[0450] (c) The second inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0451] (d) The enteric disintegration matrix comprises about 59 wt% - about 69 wt% of HPMCAS, about 29 wt% - about 39 wt% of PCL, about 0.5 wt% - about 5 wt% of poloxamer (e.g., P407), and optionally about 0.01 wt% - about 0.2 wt% of iron oxide (e.g., E172);

[0452] (e) The third inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0453] (f) The fourth inert segment comprises about 61 wt% - about 71 wt% of PCL, about 27 wt% - about 37 wt% of copovidone, about 0.2 wt% - about 4 wt% of poloxamer, and optionally about 0.005 wt% - about 0.2 wt% of a color - absorbing dye FD&C blue #1; and / or

[0454] (g) The fifth inert segment comprises about 35 wt% - about 45 wt% of PCL, about 37 wt% - about 47 wt% of copovidone, about 10 wt% - about 20 wt% of polyethylene glycol, about 1 wt% - about 5 wt% of poloxamer, and optionally about 0.0005 wt% - about 0.02 wt% of color-absorbing dye E172.

[0455] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug-eluting segment, where the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment, (b) a time-dependent disintegrating matrix, (c) a second inert segment, (d) an enteric disintegrating matrix, (e) a third inert segment, (f) a fourth inert segment, and (g) a fifth inert segment, wherein:

[0456] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 45 - about 55 shore hardness value;

[0457] (a) The first inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3;

[0458] (b) The time-dependent disintegrating matrix comprises about 43 wt% - about 47 wt% of PCL, about 33 wt% - about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 15 wt% - about 20 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 1 wt% - about 3 wt% of polyethylene glycol 100k, and about 0.01 wt% - about 0.1 wt% of color-absorbing dye E172;

[0459] (c) The second inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3;

[0460] (d) The enteric disintegrating matrix comprises about 62 wt% - about 66 wt% of HPMCAS, about 32 wt% - about 36 wt% of PCL, about 1 wt% - about 3 wt% of poloxamer (e.g., P407), and optionally about 0.05 wt% - about 0.15 wt% of iron oxide (e.g., E172);

[0461] (e) The third inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3;

[0462] (f) The fourth inert segment comprises from about 64 wt% to about 69 wt% of PCL, from about 30 wt% to about 34 wt% of copovidone, from about 0.5 wt% to about 2.5 wt% of poloxamer, and optionally from about 0.01 wt% to about 0.1 wt% of the color-absorbing dye FD&C Blue #1; and / or

[0463] (g) The fifth inert segment comprises from about 38 wt% to about 42 wt% of PCL, from about 40 wt% to about 44 wt% of copovidone, from about 13 wt% to about 17 wt% of polyethylene glycol, from about 2 wt% to about 4 wt% of poloxamer, and optionally from about 0.001 wt% to about 0.01 wt% of the color-absorbing dye E172.

[0464] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, wherein the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a first inert segment, (b) a time-dependent disintegrating matrix, (c) a second inert segment, (d) an enteric disintegrating matrix, (e) a third inert segment, (f) a fourth inert segment, and (g) a fifth inert segment, wherein:

[0465] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 50 shore value;

[0466] (a) The first inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3;

[0467] (b) The time-dependent disintegrating matrix comprises about 44.95 wt% of PCL, about 35 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 18 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% of polyethylene glycol 100k, and about 0.05 wt% of the color-absorbing dye E172;

[0468] (c) The second inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3;

[0469] (d) The enteric disintegrating matrix comprises about 63.95 wt% of HPMCAS, about 33.95 wt% of PCL, about 2 wt% of poloxamer (e.g., P407), and about 0.1 wt% of iron oxide (e.g., E172);

[0470] (e) The third inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3;

[0471] (f) The fourth inert segment comprises about 66.45 wt% of PCL, about 32 wt% of copovidone, about 1.5 wt% of poloxamer, and optionally about 0.05 wt% of the color-absorbing dye FD&C Blue #1; and / or

[0472] (g) The fifth inert segment comprises about 39.995 wt% of PCL, about 42 wt% of copovidone, about 15 wt% of polyethylene glycol, about 3 wt% of poloxamer, and optionally about 0.05 wt% of the color-absorbing dye E172.

[0473] In some embodiments of any of the gastric retention systems described herein, the gastric retention system comprises at least one arm, the arm comprising a drug-eluting segment, wherein the arm further comprises a fifth optional inert segment, wherein the fifth optional inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3. In some embodiments, the fifth optional inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)2CO3. In some embodiments, the fifth optional inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)2CO3.

[0474] In any of the above embodiments, the arm may be attached to the central elastomer at the first inert segment. That is, the first inert segment is the proximal end of the arm.

[0475] The following table provides a list of the lengths of each segment in the drug-eluting arms of the gastric retention system. Each of the following ranges or values may be considered "approximate" the indicated range or value, or exactly the indicated range or value.

[0476] Segment Length Drug eluting segment 2.4 mm Fourth inert segment 5.6 mm First, second, third or fifth inert segment 0.5 mm Enteric disintegration matrix 1.85 mm Time-dependent disintegration matrix 1.00 mm Fifth inert segment 4 mm

[0477] The following table provides a list of the lengths of each segment in the drug-free arms of the gastric retention system. Each of the following ranges or values may be considered "approximate" the indicated range or value, or exactly the indicated range or value.

[0478] Segment Length Fourth inert segment 8 mm First, second, third or fifth inert segment 0.5 mm Enteric disintegration matrix 1.85 mm Time-dependent disintegration matrix 1.00 mm Fifth inert segment 4 mm

[0479] The above gastric retention system, although described as formulated with risperidone, is not limited thereto and may be used with other drugs by replacing the segment containing risperidone and / or replacing the inert segments with segments containing other drugs.

[0480] The following gastric retention systems are exemplary in order to better illustrate embodiments of the systems described herein.

[0481] In some embodiments, the gastric retention system comprises at least one arm, the arm including a drug eluting segment, wherein the arm comprises: (a) a timed disintegration matrix as described in any of the foregoing embodiments, (b) a first inert segment as described in any of the embodiments of the inert segment above, (c) an enteric disintegration matrix as described in any of the foregoing embodiments, (d) a second inert segment as described in any of the embodiments of the inert segment above, (e) a drug eluting segment as described in any of the foregoing embodiments, and (f) a third inert segment as described in any of the embodiments of the inert segment above. The timed disintegration matrix may be attached to the central elastomer.

[0482] In some embodiments, the gastric retention system comprises at least one arm, the arm including a drug eluting segment, wherein the arm comprises: (a) a timed disintegration matrix as described in any of the foregoing embodiments (e.g., any one of T-DM / , T-DM2, T-DM3, T-DM4, T-DM5, T-DM6), (b) a first inert segment as described in any of the embodiments of the inert segment above (e.g., any one of IS-1, IS-2 or IS-3), (c) an enteric disintegration matrix as described in any of the foregoing embodiments (e.g., E-DM1 or E-DM2), (d) a second inert segment as described in any of the embodiments of the inert segment above (e.g., any one of IS-1, IS-2 or IS-3), (e) a drug eluting segment as described in any of the foregoing embodiments (e.g., CP-1), and (f) a third inert segment as described in any of the embodiments of the inert segment above (e.g., any one of IS-1, IS-2 or IS-3). The drug eluting arm may comprise an optional fourth inert segment as described in any of the embodiments of the inert segment above (e.g., any one of IS-1, IS-2 or IS-3). The segments may be arranged in any order. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (timed disintegration matrix)(first inert segment)(enteric disintegration matrix)(second inert segment)(drug eluting segment)(third inert segment). Another such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (timed disintegration matrix)(first inert segment)(enteric disintegration matrix)(second inert segment)(drug eluting segment)(optional fourth inert segment)(third inert segment). The timed disintegration matrix may be attached to the central elastomer.

[0483] In some embodiments, the filament circumferentially surrounds the gastric retention system (e.g., by connecting the distal ends of each arm). The filament that circumferentially surrounds the gastric retention system and connects one or more arms of the risperidone dosage form may be a disintegrating filament. In some embodiments, the filament comprises poly(lactic-co-glycolic acid) and / or polyglycolic acid.

[0484] In some embodiments, the gastric retention system comprises at least one arm that includes a drug eluting segment, where the arm may be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegration matrix, (b) a first inert segment, (c) an enteric disintegration matrix, (d) a second inert segment, (e) a drug eluting segment, and (f) a third inert segment, where:

[0485] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 40 - about 65 shore hardness;

[0486] (a) The timed disintegration matrix comprises about 40 wt% - about 50 wt% PCL, about 30 wt% - about 40 wt% of an acid - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 10 wt% - about 25 wt% of an ester - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 0.5 wt% - about 5 wt% polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of an absorbent color dye E172;

[0487] (b) The first inert segment comprises about 65 wt% - about 75 wt% PCL and about 25 wt% - about 35 wt% (BiO)2CO3;

[0488] (c) The enteric disintegration matrix comprises about 59 wt% - about 69 wt% HPMCAS, about 29 wt% - about 39 wt% PCL, and about 0.5 wt% - about 5 wt% poloxamer (e.g., P407);

[0489] (d) The second inert segment comprises about 65 wt% - about 75 wt% PCL and about 25 wt% - about 35 wt% (BiO)2CO3;

[0490] (e) The drug eluting segment comprises about 30 wt% - about 40 wt% risperidone, about 51 wt% - about 61 wt% PCL, about 2 wt% - about 8 wt% VA64, about 1 wt% - about 5 wt% P407, about 0.1 wt% - about 1 wt% vitamin E succinate, about 0.1 wt% - about 1 wt% SiO2, and about 0.01 wt% - about 0.5 wt% pigment; and / or

[0491] (f) The third inert segment comprises about 61 wt% - about 71 wt% PCL, about 27 wt% - about 37 wt% copovidone, about 0.2 wt% - about 4 wt% poloxamer, and optionally about 0.005 wt% - about 0.2 wt% of an absorbent color dye FD&C blue #1.

[0492] In some embodiments, the gastric retention system comprises at least one arm, the arm comprising a drug eluting segment, wherein the arm may be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegrating matrix, (b) a first inert segment, (c) an enteric disintegrating matrix, (d) a second inert segment, (e) a drug eluting segment, and (f) a third inert segment, wherein:

[0493] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 40 - about 65 Shore hardness;

[0494] (a) The timed disintegrating matrix comprises about 45 wt% - about 55 wt% PCL, about 27 wt% - about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 10 wt% - about 22 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 0.5 wt% - about 5 wt% polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color-absorbing dye E172;

[0495] (b) The first inert segment comprises about 65 wt% - about 75 wt% PCL and about 25 wt% - about 35 wt% (BiO)2CO3;

[0496] (c) The enteric disintegrating matrix comprises about 59 wt% - about 69 wt% HPMCAS, about 29 wt% - about 39 wt% PCL, and about 0.5 wt% - about 5 wt% poloxamer (e.g., P407);

[0497] (d) The second inert segment comprises about 65 wt% - about 75 wt% PCL and about 25 wt% - about 35 wt% (BiO)2CO3;

[0498] (e) The drug eluting segment comprises about 30 wt% - about 40 wt% risperidone, about 51 wt% - about 61 wt% PCL, about 2 wt% - about 8 wt% VA64, about 1 wt% - about 5 wt% P407, about 0.1 wt% - about 1 wt% vitamin E succinate, about 0.1 wt% - about 1 wt% SiO2, and about 0.01 wt% - about 0.5 wt% pigment; and / or

[0499] (f) The third inert segment comprises about 61 wt% - about 71 wt% PCL, about 27 wt% - about 37 wt% crospovidone, about 0.2 wt% - about 4 wt% poloxamer, and optionally about 0.005 wt% - about 0.2 wt% of a color-absorbing dye FD&C blue #1.

[0500] In some embodiments, the gastric retention system comprises at least one arm that includes a drug eluting segment, where the arm may be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegration matrix, (b) a first inert segment, (c) an enteric disintegration matrix, (d) a second inert segment, (e) a drug eluting segment, and (f) a third inert segment, where:

[0501] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 45 - about 55 durometer;

[0502] (a) The time - dependent disintegration matrix comprises about 43 wt% - about 47 wt% PCL, about 33 wt% - about 37 wt% of an acid - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 15 wt% - about 20 wt% of an ester - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 1 wt% - about 3 wt% polyethylene glycol 100k, and about 0.01 wt% - about 0.1 wt% of an absorption color dye E172;

[0503] (b) The first inert segment comprises about 68 wt% - about 72 wt% PCL and about 28 wt% - about 32 wt% (BiO)2CO3;

[0504] (c) The enteric disintegration matrix comprises about 62 wt% - about 66 wt% HPMCAS, about 32 wt% - about 36 wt% PCL, and about 1 wt% - about 3 wt% poloxamer (e.g., P407);

[0505] (d) The second inert segment comprises about 68 wt% - about 72 wt% PCL and about 28 wt% - about 32 wt% (BiO)2CO3;

[0506] (e) The drug eluting segment comprises about 33 wt% - about 37 wt% risperidone, about 54 wt% - about 58 wt% PCL, about 4 wt% - about 6 wt% VA64, about 2 wt% - about 4 wt% P407, about 0.2 wt% - about 0.8 wt% vitamin E succinate, about 0.2 wt% - about 0.8 wt% SiO2, and about 0.05 wt% - about 0.15 wt% pigment; and / or

[0507] (f) The third inert segment comprises about 64 wt% - about 69 wt% PCL, about 30 wt% - about 34 wt% copovidone, about 0.5 wt% - about 2.5 wt% poloxamer, and optionally about 0.01 wt% - about 0.1 wt% of an absorption color dye FD&C blue #1.

[0508] In some embodiments, the gastric retention system comprises at least one arm, the arm comprising a drug eluting segment, wherein the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegrating matrix, (b) a first inert segment, (c) an enteric disintegrating matrix, (d) a second inert segment, (e) a drug eluting segment, and (f) a third inert segment, wherein:

[0509] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 45 - about 55 Shore hardness value;

[0510] (a) The time - dependent disintegrating matrix comprises about 48 wt% - about 52 wt% PCL, about 30 wt% - about 34 wt% of an acid - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 14 wt% - about 18 wt% of an ester - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 1 wt% - about 3 wt% polyethylene glycol 100k, and about 0.01 wt% - about 0.1 wt% of an absorption color dye E172;

[0511] (b) The first inert segment comprises about 68 wt% - about 72 wt% PCL and about 28 wt% - about 32 wt% (BiO)2CO3;

[0512] (c) The enteric disintegrating matrix comprises about 62 wt% - about 66 wt% HPMCAS, about 32 wt% - about 36 wt% PCL, and about 1 wt% - about 3 wt% poloxamer (e.g., P407);

[0513] (d) The second inert segment comprises about 68 wt% - about 72 wt% PCL and about 28 wt% - about 32 wt% (BiO)2CO3;

[0514] (e) The drug eluting segment comprises about 33 wt% - about 37 wt% risperidone, about 54 wt% - about 58 wt% PCL, about 4 wt% - about 6 wt% VA64, about 2 wt% - about 4 wt% P407, about 0.2 wt% - about 0.8 wt% vitamin E succinate, about 0.2 wt% - about 0.8 wt% SiO2, and about 0.05 wt% - about 0.15 wt% pigment; and / or

[0515] (f) The third inert segment comprises about 64 wt% - about 69 wt% PCL, about 30 wt% - about 34 wt% crospovidone, about 0.5 wt% - about 2.5 wt% poloxamer, and optionally about 0.01 wt% - about 0.1 wt% of an absorption color dye FD&C blue #1.

[0516] In some embodiments, the gastric retention system comprises at least one arm, the arm comprising a drug eluting segment, wherein the arm may be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegrating matrix, (b) a first inert segment, (c) an enteric disintegrating matrix, (d) a second inert segment, (e) a drug eluting segment, and (f) a third inert segment, wherein:

[0517] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 50 Shore value;

[0518] (a) The time-dependent disintegrating matrix comprises about 44.95 wt% PCL, about 35 wt% acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 18 wt% ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% polyethylene glycol 100k, and about 0.05 wt% color-absorbing dye E172;

[0519] (b) The second inert segment comprises about 70 wt% PCL and about 30 wt% (BiO)2CO3;

[0520] (c) The enteric disintegrating matrix comprises about 63.95 wt% HPMCAS, about 33.95 wt% PCL, and about 2 wt% poloxamer (e.g., P407);

[0521] (d) The second inert segment comprises about 70 wt% PCL and about 30 wt% (BiO)2CO3;

[0522] (e) The drug eluting segment comprises about 35.0 wt% risperidone, about 55.9 wt% PCL, about 5.0 wt% VA64, about 3.0 wt% P407, about 0.5 wt% vitamin E succinate, about 0.5 wt% SiO2, and about 0.1 wt% pigment; and / or

[0523] (f) The third inert segment comprises about 66.45 wt% PCL, about 32 wt% crospovidone, about 1.5 wt% poloxamer, and optionally about 0.05 wt% color-absorbing dye FD&C blue #1.

[0524] In some embodiments, the gastric retention system includes at least one arm, the arm including a drug eluting segment, where the arm can be attached to a central elastomer, and the arm includes one or more of the following: (a) a timed disintegration matrix, (b) a first inert segment, (c) an enteric disintegration matrix, (d) a second inert segment, (e) a drug eluting segment, and (f) a third inert segment, where:

[0525] The central elastomer includes liquid silicone rubber (LSR) having a hardness of about 50 shore value;

[0526] (a) The time-dependent disintegration matrix includes about 49.95 wt% PCL, about 32 wt% acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 16 wt% ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% polyethylene glycol 100k, and about 0.05 wt% color-absorbing dye E172;

[0527] (b) The second inert segment includes about 70 wt% PCL and about 30 wt% (BiO)2CO3;

[0528] (c) The enteric disintegration matrix includes about 63.95 wt% HPMCAS, about 33.95 wt% PCL, and about 2 wt% poloxamer (e.g., P407);

[0529] (d) The second inert segment includes about 70 wt% PCL and about 30 wt% (BiO)2CO3;

[0530] (e) The drug eluting segment includes about 35.0 wt% risperidone, about 55.9 wt% PCL, about 5.0 wt% VA64, about 3.0 wt% P407, about 0.5 wt% vitamin E succinate, about 0.5 wt% SiO2, and about 0.1 wt% pigment; and / or

[0531] (f) The third inert segment includes about 66.45 wt% PCL, about 32 wt% crospovidone, about 1.5 wt% poloxamer, and optionally about 0.05 wt% color-absorbing dye FD&C blue #1.

[0532] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, wherein the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegrating matrix as described in any of the above embodiments, (b) a first inert segment as described in any of the above embodiments of the inert segment, (c) an enteric disintegrating matrix as described in any of the above embodiments, (d) a second inert segment as described in any of the above embodiments of the inert segment, and (e) a third inert segment as described in any of the above embodiments of the inert segment. The timed disintegrating matrix can be attached to the central elastomer.

[0533] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, wherein the arm comprises: (a) a timed disintegrating matrix as described in any of the above embodiments (e.g., any one of T-DM / , T-DM2, T-DM3, T-DM4, T-DM5, T-DM6), (b) a first inert segment as described in any of the above embodiments of the inert segment (e.g., any one of IS-1, IS-2 or IS-3), (c) an enteric disintegrating matrix as described in any of the above embodiments (e.g., E-DM1 or E-DM2), (d) a second inert segment as described in any of the above embodiments of the inert segment (e.g., any one of IS-1, IS-2 or IS-3), and (e) a third inert segment as described in any of the above embodiments of the inert segment (e.g., any one of IS-1, IS-2 or IS-3). The drug-free arm can comprise an optional fourth inert segment as described in any of the above embodiments of the inert segment (e.g., any one of IS-1, IS-2 or IS-3). The segments can be arranged in any order. One such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (timed disintegrating matrix)(first inert segment)(enteric disintegrating matrix)(second inert segment)(third inert segment). Another such order is, starting from the proximal end attached to the central elastomer and proceeding distally: (timed disintegrating matrix)(first inert segment)(enteric disintegrating matrix)(second inert segment)(optional fourth inert segment)(third inert segment). The timed disintegrating matrix can be attached to the central elastomer.

[0534] In some embodiments, a filament circumferentially surrounds the gastric retention system (e.g., by connecting the distal ends of each arm). The filament that circumferentially surrounds the gastric retention system and connects one or more arms of the risperidone dosage form can be a disintegrating filament. In some embodiments, the filament comprises poly(lactic-co-glycolic acid) and / or polyglycolic acid.

[0535] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, wherein the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegration matrix, (b) a first inert segment, (c) an enteric disintegration matrix, (d) a second inert segment, (e) a drug eluting segment, and (f) a third inert segment, wherein:

[0536] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 40 - about 65 shore hardness;

[0537] (a) The timed disintegration matrix comprises about 40 wt% - about 50 wt% PCL, about 30 wt% - about 40 wt% of an acid - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 10 wt% - about 25 wt% of an ester - terminated copolymer of DL - lactide and glycolide (50 / 50 molar ratio) having a viscosity mid - point of about 0.4 dl / g, about 0.5 wt% - about 5 wt% polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of an absorption - color dye E172;

[0538] (b) The first inert segment comprises about 65 wt% - about 75 wt% PCL and about 25 wt% - about 35 wt% (BiO)₂CO₃;

[0539] (c) The enteric disintegration matrix comprises about 59 wt% - about 69 wt% HPMCAS, about 29 wt% - about 39 wt% PCL, and about 0.5 wt% - about 5 wt% poloxamer (e.g., P407);

[0540] (d) The second inert segment comprises about 65 wt% - about 75 wt% PCL and about 25 wt% - about 35 wt% (BiO)₂CO₃; and / or

[0541] (e) The third inert segment comprises about 61 wt% - about 71 wt% PCL, about 27 wt% - about 37 wt% copovidone, about 0.2 wt% - about 4 wt% poloxamer, and optionally about 0.005 wt% - about 0.2 wt% of an absorption - color dye FD&C blue #1.

[0542] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, wherein the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegration matrix, (b) a first inert segment, (c) an enteric disintegration matrix, (d) a second inert segment, and (e) a third inert segment, wherein:

[0543] The central elastomer comprises a liquid silicone rubber (LSR) having a hardness value of about 40 - about 65;

[0544] (a) The timed disintegration matrix comprises about 45 wt% - about 55 wt% of PCL, about 27 wt% - about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 10 wt% - about 22 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 0.5 wt% - about 5 wt% of polyethylene glycol 100k, and about 0.005 wt% - about 0.2 wt% of a color-absorbing dye E172;

[0545] (b) The first inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3;

[0546] (c) The enteric disintegration matrix comprises about 59 wt% - about 69 wt% of HPMCAS, about 29 wt% - about 39 wt% of PCL, and about 0.5 wt% - about 5 wt% of poloxamer (e.g., P407);

[0547] (d) The second inert segment comprises about 65 wt% - about 75 wt% of PCL and about 25 wt% - about 35 wt% of (BiO)2CO3; and / or

[0548] (e) The third inert segment comprises about 61 wt% - about 71 wt% of PCL, about 27 wt% - about 37 wt% of copovidone, about 0.2 wt% - about 4 wt% of poloxamer, and optionally about 0.005 wt% - about 0.2 wt% of a color-absorbing dye FD&C blue #1.

[0549] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug eluting segment, wherein the arm can be attached to the central elastomer, and the arm comprises one or more of the following: (a) a timed disintegration matrix, (b) a first inert segment, (c) an enteric disintegration matrix, (d) a second inert segment, and (e) a third inert segment, wherein:

[0550] The central elastomer comprises a liquid silicone rubber (LSR) having a hardness value of about 45 - about 55;

[0551] (a) The time-dependent disintegration matrix comprises from about 43 wt% to about 47 wt% of PCL, from about 33 wt% to about 37 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, from about 15 wt% to about 20 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, from about 1 wt% to about 3 wt% of polyethylene glycol 100k, and from about 0.01 wt% to about 0.1 wt% of a color-absorbing dye E172;

[0552] (b) The first inert segment comprises from about 68 wt% to about 72 wt% of PCL and from about 28 wt% to about 32 wt% of (BiO)2CO3;

[0553] (c) The enteric disintegration matrix comprises from about 62 wt% to about 66 wt% of HPMCAS, from about 32 wt% to about 36 wt% of PCL, and from about 1 wt% to about 3 wt% of poloxamer (e.g., P407);

[0554] (d) The second inert segment comprises from about 68 wt% to about 72 wt% of PCL and from about 28 wt% to about 32 wt% of (BiO)2CO3; and / or

[0555] (e) The third inert segment comprises from about 64 wt% to about 69 wt% of PCL, from about 30 wt% to about 34 wt% of copovidone, from about 0.5 wt% to about 2.5 wt% of poloxamer, and optionally from about 0.01 wt% to about 0.1 wt% of a color-absorbing dye FD&C blue #1.

[0556] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug-eluting segment, wherein the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegration matrix, (b) a first inert segment, (c) an enteric disintegration matrix, (d) a second inert segment, and (e) a third inert segment, wherein:

[0557] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 45 - about 55 shore hardness;

[0558] (a) The time-dependent disintegration matrix comprises about 48 wt% - about 52 wt% of PCL, about 30 wt% - about 34 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 14 wt% - about 18 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 1 wt% - about 3 wt% of polyethylene glycol 100k, and about 0.01 wt% - about 0.1 wt% of a color-absorbing dye E172;

[0559] (b) The first inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)₂CO₃;

[0560] (c) The enteric disintegration matrix comprises about 62 wt% - about 66 wt% of HPMCAS, about 32 wt% - about 36 wt% of PCL, and about 1 wt% - about 3 wt% of poloxamer (e.g., P407);

[0561] (d) The second inert segment comprises about 68 wt% - about 72 wt% of PCL and about 28 wt% - about 32 wt% of (BiO)₂CO₃; and / or

[0562] (e) The third inert segment comprises about 64 wt% - about 69 wt% of PCL, about 30 wt% - about 34 wt% of copovidone, about 0.5 wt% - about 2.5 wt% of poloxamer, and optionally about 0.01 wt% - about 0.1 wt% of a color-absorbing dye FD&C Blue #1.

[0563] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug-eluting segment, where the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegration matrix, (b) a first inert segment, (c) an enteric disintegration matrix, (d) a second inert segment, and (e) a third inert segment, where:

[0564] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 50 Shore value;

[0565] (a) The time-dependent disintegration matrix, the time-dependent disintegration matrix comprises about 44.95 wt% of PCL, about 35 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 18 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% of polyethylene glycol 100k, and about 0.05 wt% of a color-absorbing dye E172;

[0566] (b) The second inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)₂CO₃;

[0567] (c) The enteric disintegration matrix comprises about 63.95 wt% of HPMCAS, about 33.95 wt% of PCL, and about 2 wt% of poloxamer (e.g., P407);

[0568] (d) The second inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)₂CO₃; and / or

[0569] (e) The third inert segment comprises about 66.45 wt% of PCL, about 32 wt% of copovidone, about 1.5 wt% of poloxamer, and optionally about 0.05 wt% of the color-absorbing dye FD&C Blue #1.

[0570] In some embodiments, the gastric retention system comprises at least one arm that does not include a drug-eluting segment, wherein the arm can be attached to a central elastomer, and the arm comprises one or more of the following: (a) a timed disintegration matrix, (b) a first inert segment, (c) an enteric disintegration matrix, (d) a second inert segment, and (e) a third inert segment, wherein:

[0571] The central elastomer comprises liquid silicone rubber (LSR) having a hardness of about 50 Shore value;

[0572] (a) A time-dependent disintegration matrix that comprises about 49.95 wt% of PCL, about 32 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 16 wt% of an ester-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.4 dl / g, about 2 wt% of polyethylene glycol 100k, and about 0.05 wt% of the color-absorbing dye E172;

[0573] (b) The second inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)₂CO₃;

[0574] (c) The enteric disintegration matrix comprises about 63.95 wt% of HPMCAS, about 33.95 wt% of PCL, and about 2 wt% of poloxamer (e.g., P407);

[0575] (d) The second inert segment comprises about 70 wt% of PCL and about 30 wt% of (BiO)₂CO₃; and / or

[0576] (e) The third inert segment comprises about 66.45 wt% PCL, about 32 wt% copovidone, about 1.5 wt% poloxamer, and optionally about 0.05 wt% of the color-absorbing dye FD&C Blue #1.

[0577] In some embodiments of any of the gastric retention systems described herein, the gastric retention system comprises at least one arm, the arm comprising a drug eluting segment, wherein the arm may further comprise a fourth optional inert segment, wherein the fourth optional inert segment comprises about 65 wt% - about 75 wt% PCL and about 25 wt% - about 35 wt% (BiO)2CO3. In some embodiments, the fourth optional inert segment comprises about 68 wt% - about 72 wt% PCL and about 28 wt% - about 32 wt% (BiO)2CO3. In some embodiments, the fourth optional inert segment comprises about 70 wt% PCL and about 30 wt% (BiO)2CO3.

[0578] In any of the above embodiments, the arm may be attached to the central elastomer at the first inert segment. That is, the first inert segment is the proximal end of the arm.

[0579] The following table provides a list of the lengths of each segment in the drug eluting arm of the gastric retention system. Each of the following ranges or values may be considered "approximate" the indicated range or value, or exactly the indicated range or value.

[0580] Segment Length Drug eluting segment 7.8 mm Third inert segment 5.3 mm First, second or fourth inert segment 0.5 mm Enteric disintegration matrix 1.85 mm Time-dependent disintegration matrix 1.00 mm

[0581] The following table provides a list of the lengths and thicknesses of each segment in the drug eluting arm of the gastric retention system. Each of the following ranges or values may be considered "approximate" the indicated range or value, or exactly the indicated range or value.

[0582]

[0583]

[0584] The following table provides a list of the lengths and thicknesses of each segment in the drug eluting arm of the gastric retention system. Each of the following ranges or values may be considered "approximate" the indicated range or value, or exactly the indicated range or value.

[0585] Segment Length Thickness Drug eluting segment 7.8 mm 3.3 mm Third inert segment 5.3 mm 3.1 mm First, second or fourth inert segment 0.5 mm 3.3 mm Enteric disintegration matrix 1.85 mm 3.3 mm Time-dependent disintegration matrix 1.00 mm 3.3 mm

[0586] The following table provides a list of the lengths of each segment in the drug-free arm of the gastric retention system. Each of the following ranges or values may be considered "approximate" the indicated range or value, or exactly the indicated range or value.

[0587] Segment Length Third inert segment 13.1 mm First, second or fourth inert segment 0.5 mm Enteric disintegration matrix 1.85 mm Time-dependent disintegration matrix 1.00 mm

[0588] The following table provides a list of the lengths and thicknesses of each section in the drug-free arm of the gastric retention system. Each of the following ranges or values can be considered to be "approximate" the indicated range or value, or exactly the indicated range or value.

[0589] Segment Length Thickness Third inert segment 13.1 mm 3.3 mm First, second or fourth inert segment 0.5 mm 3.3 mm Enteric disintegration matrix 1.85 mm 3.3 mm Time-dependent disintegration matrix 1.00 mm 3.3 mm

[0590] The following table provides a list of the lengths and thicknesses of each section in the drug-free arm of the gastric retention system. Each of the following ranges or values can be considered to be "approximate" the indicated range or value, or exactly the indicated range or value.

[0591] Segment Length Thickness Third inert segment 13.1 mm 3.1 mm First, second or fourth inert segment 0.5 mm 3.3 mm Enteric disintegration matrix 1.85 mm 3.3 mm Time-dependent disintegration matrix 1.00 mm 3.3 mm

[0592] In some embodiments of any of the systems described herein, the thickness of a section is determined by the longest straight line within the cross-section of the section. In some embodiments in which the cross-section of the section is circular, the thickness is defined by the diameter of the circle. In some embodiments in which the cross-section of the section is square or rectangular, the thickness is defined by the diagonal of the square or rectangle. In some embodiments in which the cross-section of the section is an equilateral triangle, the thickness is defined by the side of the equilateral triangle.

[0593] The above gastric retention system, although described as formulated with risperidone, is not limited thereto and can be used with other drugs by replacing the section containing risperidone with a section containing other drugs and / or replacing the inert section.

[0594] In some embodiments, the dosage form for administering risperidone comprises a gastric retention system, wherein the gastric retention system comprises one or two inactive segments. In some embodiments, the gastric retention system comprises a first inactive segment that comprises about 66.495 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the gastric retention system comprises a first inactive segment that comprises about 32.0 wt% of copovidone, such as VA64. In some embodiments, the gastric retention system comprises a first inactive segment that comprises about 1.5 wt% of a poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(O-CH(CH3)CH2)y-(OCH2CH2)z-OH, where x and z are about 101 and y is about 56, such as poloxamer 407 (P407). In some embodiments, the gastric retention system comprises a first inactive segment that comprises about 0.005 wt% of iron oxide, such as E172. In some embodiments, the gastric retention system comprises a second inactive segment that comprises about 39.995 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the gastric retention system comprises a second inactive segment that comprises about 42.0 wt% of copovidone, such as VA64. In some embodiments, the gastric retention system comprises a second inactive segment that comprises about 15.0 wt% of polyethylene glycol, such as polyethylene glycol having an average molecular weight of 100,000, such as PEO 100K. In some embodiments, the gastric retention system comprises a second inactive segment that comprises about 3.0 wt% of a poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(O-CH(CH3)CH2)y-(OCH2CH2)z-OH, where x and z are about 101 and y is about 56, such as poloxamer 407 (P407). In some embodiments, the gastric retention system comprises a second inactive segment that comprises about 0.005 wt% of iron oxide, such as E172. In some embodiments, the dosage form for administering risperidone comprises a gastric retention system, wherein the gastric retention system comprises one or two inactive segments. In some embodiments, the gastric retention system comprises a first inactive segment that comprises about 66.45 wt% of Corbion PC17, about 32.0 wt% of VA64, about 1.5 wt% of P407, and about 0.05 wt% of FD&C Blue 1 Aluminum Lake. In some embodiments, the gastric retention system comprises a second inactive segment that comprises about 39.995 wt% of Corbion PC17, about 42.0 wt% of VA64, about 15.0 wt% of PEO 100K , about 3.0 wt% of P407, and about 0.005 wt% of E172.

[0595] . In some embodiments, the gastric retention system dosage form for administering one or more active agents may comprise a radiopaque segment, wherein the segment comprises about 70 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the gastric retention system comprises a radiopaque segment that comprises about 30 wt% of (BiO)2CO3. In some embodiments, the gastric retention system comprises a radiopaque segment that comprises about 70 wt% of Corbion PC17 and about 30 wt% of (BiO)2CO3.

[0596] In some embodiments, the gastric retention system dosage form for administering risperidone comprises a central elastomer and a drug eluting segment, and the drug eluting segment comprises about 14 mg of risperidone. In some embodiments, the dosage form comprises a gastric retention system, wherein the gastric retention system comprises a drug eluting segment, and the drug eluting segment comprises about 28 mg of risperidone. In some embodiments, the gastric retention system further comprises a rate-modulating film which comprises about 73.5 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the rate-modulating film further comprises about 24.5 wt% of copovidone, such as VA64. In some embodiments, the rate-modulating film further comprises about 2.0 wt% of magnesium stearate. In some embodiments, the gastric retention system further comprises a time-dependent disintegration matrix, and the time-dependent disintegration matrix comprises about 44.95 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the time-dependent disintegration matrix further comprises about 35.0 wt% of an acid-terminated copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), such as PDLG 5004A. In some embodiments, the time-dependent disintegration matrix further comprises about 18.0 wt% of a copolymer of DL-lactide and glycolide (50 / 50 molar ratio) having a viscosity midpoint of about 0.32 dl / g - about 0.48 dl / g (such as about 0.4 dl / g), such as PDLG 5004. In some embodiments, the time-dependent disintegration matrix further comprises about 2.0 wt% of polyethylene glycol, such as polyethylene glycol having an average molecular weight of 100,000, such as PEO 100K. In some embodiments, the time-dependent disintegration matrix further comprises about 0.05 wt% of iron oxide, such as E172. In some embodiments, the gastric retention system further comprises a pH-dependent disintegration matrix, which comprises about 33.95 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the pH-dependent disintegration matrix further comprises about 63.95 wt% of hypromellose acetate succinate, such as HPMCAS-MG. In some embodiments, the pH-dependent disintegration matrix further comprises about 2.0 wt% of a poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer, such as H-(OCH2CH2)x-(O-CH(CH3)CH2)y-(OCH2CH2)z-OH, where x and z are about 101 and y is about 56, such as poloxamer 407 (P407). In some embodiments, the pH-dependent disintegration matrix further comprises about 0.1 wt% of iron oxide, such as E172. In some embodiments, the gastric retention system further comprises one or more inactive segments. In some embodiments, the gastric retention system further comprises a radiopaque segment, which comprises about 70 wt% of polycaprolactone (PCL), such as PCL having a viscosity midpoint of about 1.5 dl / g - about 2.1 dl / g, such as Corbion PC17. In some embodiments, the radiopaque segment comprises about 30 wt% of (BiO)2CO3. In some embodiments, the dosage form for administering risperidone comprises a gastric retention system, wherein the gastric retention system comprises a central elastomer and a drug eluting segment, which comprises about 14 mg of risperidone. In some embodiments, the dosage form comprises a gastric retention system, wherein the gastric retention system comprises a drug eluting segment, and the drug eluting segment comprises about 28 mg of risperidone. In some embodiments, the gastric retention system further comprises a rate-regulating release film, which comprises about 73.5 wt% of Corbion PC17, about 24.5 wt% of VA64 and about 2.0 wt% of magnesium stearate. In some embodiments, the gastric retention system further comprises a time-dependent disintegration matrix, which comprises about 44.95 wt% of Corbion PC17, about 35.0 wt% of PDLG 5004A, about 18.0 wt% of PDLG 5004, about 2.0 wt% of PEO 100KIn some embodiments, the gastric resident system further comprises a pH-dependent disintegrating matrix comprising about 33.95wt% Corbion PC17, about 63.95wt% PMCAS-MG, about 2.0wt% P407, and about 0.1wt% E172. In some embodiments, the gastric resident system further comprises one or more inactive segments. In some embodiments, the gastric resident system further comprises a radiopaque segment comprising about 70wt% Corbion PC17 and about 30wt% (BiO)2CO3.

[0597] In some embodiments, the gastric resident system has three arms that contain a drug eluting segment and three arms that do not contain a drug eluting segment. In some embodiments, the gastric resident system has six arms that contain a drug eluting segment.

[0598] In some embodiments of any of the systems described herein, the thickness of a segment is determined by the longest straight line within the cross section of the segment. In some embodiments where the cross section of the segment is circular, the thickness is defined by the diameter of the circle. In some embodiments where the cross section of the segment is square or rectangular, the thickness is defined by the diagonal of the square or rectangle. In some embodiments where the cross section of the segment is an equilateral triangle, the thickness is defined by the sides of the equilateral triangle.

[0599] In some embodiments of any system described herein, the thickness of the segment of the entire star arm is uniform. In some embodiments of any system described herein, the thickness of the segment of the entire star arm is about 2.8mm-about 3.7mm, optionally about 3.1mm-3.5mm, and more optionally about 3.3mm.

[0600] In some embodiments of any of the systems described herein, the thickness of one or more segments at the distal end of the arm (furthest from the star core) is less than the thickness of the remaining proximal segments in the arm, where optionally, the thickness of the proximal segments can be uniform. In some embodiments of any of the systems described herein, the thickness of the furthest segment is from about 2.4 mm to about 3.4 mm, where the thickness of the remaining segments in the arm is from about 2.8 mm to about 3.7 mm. In some embodiments, the thickness of the furthest segment is from about 2.8 mm to about 3.1 mm, where the thickness of the remaining segments in the arm is from 3.1 mm to about 3.5 mm. In some embodiments of any of the systems described herein, the thickness of the furthest segment is from about 2.9 mm to about 3.2 mm, where the thickness of the remaining segments in the arm is from about 3.2 mm to about 3.5 mm. In some embodiments, the thickness of the furthest segment is from about 2.9 mm to about 3.15 mm, where the thickness of the remaining segments in the arm is from about 3.2 mm to about 3.4 mm. In some embodiments, the thickness of the furthest segment is about 3.1 mm, where the thickness of the remaining segments in the arm is about 3.3 mm.

[0601] Central elastomer

[0602] The central elastomer provides the gastric retention system with the ability to be compacted into a compressed configuration, which can be placed in a capsule or other suitable containment structure for administration to an individual.

[0603] In some embodiments, a dosage form for administering one or more active agents comprises a gastric retention system, where the gastric retention system comprises a central elastomer, which comprises liquid silicone rubber (LSR). In some embodiments, the LSR has a hardness with a hardness value of about 45 - about 60.

[0604] In some embodiments, a dosage form for administering one or more active agents comprises a gastric retention system, where the gastric retention system comprises a central elastomer, which comprises liquid silicone rubber (LSR). In some embodiments, the LSR has a hardness with a hardness value of about 45 - about 55.

[0605] In some embodiments, a dosage form for administering one or more active agents comprises a gastric retention system, where the gastric retention system comprises a central elastomer, which comprises liquid silicone rubber (LSR). In some embodiments, the LSR has a hardness with a hardness value of about 60.

[0606] In some embodiments, a dosage form for administering one or more active agents comprises a gastric retention system, where the gastric retention system comprises a central elastomer, which comprises liquid silicone rubber (LSR). In some embodiments, the LSR has a hardness with a hardness value of about 50.

[0607] Rate - modulating polymer film

[0608] A polymer film that modulates the release rate can be coated on components of a gastric retention system that releases an active agent such as a drug. The components coated with the polymer film that modulates the release rate disclosed herein have substantially the same release rate properties before and after exposure to heating, which occurs during the heat-assisted assembly of the gastric retention system. The composition, parameters, advantages, features, applications, and release characteristics of the polymer film that modulates the release rate are disclosed in International Patent Application PCT / US2020 / 059541 (WO 2021 / 092491), the entire content of which is incorporated herein by reference. In some embodiments, one or more segments of the composite arm (such as a composite arm that includes a drug eluting segment or a composite arm that does not include a drug eluting segment) are coated with a film that modulates the release rate. In some embodiments, the drug eluting segment is coated with a film that modulates the release rate. In some embodiments, one or more inert segments are coated with a film that modulates the release rate. In some embodiments, the film that modulates the release rate is applied in an amount of about 0.5% - about 10% or about 1% - about 5%, such as about 2% - about 4%, of the pre-coated weight of the segment (such as the drug eluting segment and / or the inert segment). In some embodiments, the film that modulates the release rate is applied in an amount of about 2.3% - about 3%, such as about 2.6%, of the pre-coated weight of the segment (such as the drug eluting segment and / or the inert segment). In some embodiments, the film that modulates the release rate is applied in an amount of about 2.4% - about 3.2, such as about 2.8%, of the pre-coated weight of the segment (such as the drug eluting segment and / or the inert segment).

[0609] A variety of polymers can be used to form the polymer film that modulates the release rate, including PCL. In some embodiments, the polymer film that modulates the release rate comprises about 68 wt% - about 78 wt% of PCL. In some embodiments, the polymer film that modulates the release rate comprises about 71 wt% - about 76 wt% of PCL. In some embodiments, the polymer film that modulates the release rate comprises about 73.5 wt% of PCL.

[0610] Other excipients can be added to the carrier polymer to modulate the release of the active agent, such as copovidone (VA64). In some embodiments, the polymer film that modulates the release rate comprises about 20 wt% - about 30 wt% of VA64. In some embodiments, the polymer film that modulates the release rate comprises about 22 wt% - about 27 wt% of VA64. In some embodiments, the polymer film that modulates the release rate comprises about 24.5 wt% of VA64.

[0611] The film for adjusting the release rate may contain one or more dispersants, such as magnesium stearate. In some embodiments, the polymer film for adjusting the release rate contains about 0.5 wt% - about 5 wt% of magnesium stearate. In some embodiments, the polymer film for adjusting the release rate contains about 1 wt% - about 3 wt% of magnesium stearate. In some embodiments, the polymer film for adjusting the release rate contains about 2 wt% of magnesium stearate.

[0612] In some embodiments, the polymer film for adjusting the release rate contains about 68 wt% - about 78 wt% of PCL, about 20 wt% - about 30 wt% of VA64 and about 0.5 wt% - about 5 wt% of magnesium stearate. In some embodiments, the polymer film for adjusting the release rate contains about 71 wt% - about 76 wt% of PCL, about 22 wt% - about 27 wt% of VA64 and about 1 wt% - about 3 wt% of magnesium stearate. In some embodiments, the polymer film for adjusting the release rate contains about 73.5 wt% of PCL, about 24.5 wt% of VA64 and about 2 wt% of magnesium stearate.

[0613] The following table provides exemplary amounts of the components of the film for adjusting the release rate. The amounts are given in approximate weight percentages and it should be understood that when ranges are provided, the amounts are selected so as to total 100%.

[0614] Film for regulating release rate Formulation 1 Formulation 2 Formulation 3 PCL 67-77 71-76 73.5 VA64 20-30 22-27 24.5 Magnesium stearate 0.5-5 1-3 2.0

[0615] Encapsulation of the gastric retention system in a capsule

[0616] As described above, in Figure 1A an example of the star-shaped system 100 is schematically shown and the construction allows the system to be folded or compacted at the central elastomer. Figure IB shows the Figure 1A folded configuration 190 of the gastric retention system (for clarity, Figure 1B only two arms are illustrated in

[0617] In some embodiments, the capsule comprises a narrower portion (hereinafter referred to as the "capsule bottom") and a wider portion (hereinafter referred to as the "capsule cap", "capsule top", or "capsule sleeve"), wherein the capsule is closed by fitting the wider capsule top over the narrower capsule bottom. In some embodiments, the system is oriented within the capsule such that the star core is positioned closer to the capsule bottom, and wherein the distal tips of the star arms (and any circumferential filaments) are positioned closer to the capsule top, i.e., the capsule sleeve covers the distal tips of the star arms. In some embodiments, the system is oriented within the capsule such that the star core is positioned closer to the capsule top, and wherein the distal tips of the star arms (and any circumferential filaments) are positioned closer to the capsule bottom, i.e., the capsule sleeve covers the star core. In some embodiments, the core side sleeve provides a better fit with the disintegration filament stabilizing ring and ensures proper alignment of the stabilizing ring filaments within the capsule for full deployment.

[0618] In some embodiments, the capsule is sized 000, 00, 0, 1, 2, 3, 4, or 5. In some embodiments, the capsule size is 00EL. In some embodiments, the capsule is an HPMC capsule. In some embodiments, the capsule comprises any one of about 1%, 2%, 3%, 4%, or 5% titanium oxide. In some embodiments, the capsule is a white opaque HPMC capsule (size 00EL) with 2% titanium oxide. In some embodiments, the capsule is a white opaque HPMC capsule (size 00EL) with 3% titanium oxide.

[0619] In some embodiments, as described in Example 1 of International Patent Application PCT / US2020 / 059541 (WO 2021 / 092491), the gastric retention system is assembled and then placed in a capsule of appropriate size.

[0620] In some embodiments, as described in International Patent Application PCT / US2020 / 023704 (WO 2020 / 191229), the gastric retention system is assembled and then placed in a capsule of appropriate size.

[0621] In some embodiments, as described in International Patent Application PCT / US2020 / 023710 (WO 2020 / 191231), the gastric retention system is assembled and then placed in a capsule of appropriate size.

[0622] The entire contents of International Applications PCT / US2020 / 059541 (WO 2021 / 092491), PCT / US2020 / 023704 (WO 2020 / 191229), and PCT / US2020 / 023710 (WO 2020 / 191231) are incorporated herein by reference.

[0623] Extended Release of Pharmaceutical Dosage Forms

[0624] In some embodiments of any of the risperidone dosage forms described herein, the gastric retention system allows for extended release of risperidone (e.g., including risperidone and any of its metabolite forms).

[0625] In the dosing regimens disclosed herein, any gastric retention system containing an appropriate amount of risperidone or its salt can be used, including but not limited to the gastric retention systems for administering risperidone disclosed in International Patent Application Nos. WO 2021 / 092491 and WO 2022 / 159529. The entire contents of these patent applications are incorporated herein by reference.

[0626] In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of at least about 7.0 ng / mL at about 24 hours. In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of at least about 6.5 ng / mL at about 48 hours. In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of at least about 4.5 ng / mL at about 72 hours. In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of at least about 3.0 ng / mL at about 96 hours. In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of at least about 2.5 ng / mL at about 120 hours. In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of at least about 2.0 ng / mL at about 144 hours.

[0627] In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of no more than about 27.0 ng / mL at about 24 hours. In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of no more than about 22.5 ng / mL at about 48 hours. In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of no more than about 21.5 ng / mL at about 72 hours. In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of no more than about 21.0 ng / mL at about 96 hours. In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of no more than about 20.0 ng / mL at about 120 hours. In one embodiment, administering to a human a gastric retention dosage form containing about 14 mg of risperidone results in a plasma level of no more than about 17.0 ng / mL at about 144 hours.

[0628] In one embodiment, administration of a gastric retention dosage form comprising about 14 mg of risperidone to a human produces plasma levels of about 7.0 ng / mL - about 27.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric retention dosage form comprising about 14 mg of risperidone to a human produces plasma levels of about 6.5 ng / mL - about 22.5 ng / mL at about 48 hours. In one embodiment, administration of a gastric retention dosage form comprising about 14 mg of risperidone to a human produces plasma levels of about 4.5 ng / mL - about 21.5 ng / mL at about 72 hours. In one embodiment, administration of a gastric retention dosage form comprising about 14 mg of risperidone to a human produces plasma levels of about 3.0 ng / mL - about 21.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric retention dosage form comprising about 14 mg of risperidone to a human produces plasma levels of about 2.5 ng / mL - about 20.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric retention dosage form comprising about 14 mg of risperidone to a human produces plasma levels of about 2.0 ng / mL - about 17.0 ng / mL at about 144 hours.

[0629] In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human produces plasma levels of at least about 20.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human produces plasma levels of at least about 16.0 ng / mL at about 48 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human produces plasma levels of at least about 14.5 ng / mL at about 72 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human produces plasma levels of at least about 12.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human produces plasma levels of at least about 9.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human produces plasma levels of at least about 6.0 ng / mL at about 144 hours.

[0630] In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of no more than about 39.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of no more than about 39.0 ng / mL at about 48 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of no more than about 38.0 ng / mL at about 72 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of no more than about 35.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of no more than about 30.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of no more than about 25.0 ng / mL at about 144 hours.

[0631] In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of about 20.0 ng / mL - about 39.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of about 16.0 ng / mL - about 39.0 ng / mL at about 48 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of about 14.5 ng / mL - about 38.0 ng / mL at about 72 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of about 12.0 ng / mL - about 35.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of about 9.0 ng / mL - about 30.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric retention dosage form comprising about 28 mg of risperidone to a human results in a plasma level of about 6.0 ng / mL - about 25.0 ng / mL at about 144 hours.

[0632] In any of these embodiments, administration of the gastric retention dosage form can be carried out at least 7 days after administration of immediate-release risperidone, for example, using about 2 mg of immediate-release risperidone for at least about 7 days, or using about 4 mg of immediate-release risperidone for at least about 7 days, or using about 6 mg of immediate-release risperidone for at least about 7 days.

[0633] In some embodiments of any of the risperidone dosage forms described herein, the gastric retention system permits extended release of risperidone (e.g., including risperidone and any active metabolite forms thereof).

[0634] In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of at least about 7.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of at least about 6.5 ng / mL at about 48 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of at least about 4.5 ng / mL at about 72 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of at least about 3.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of at least about 2.5 ng / mL at about 120 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of at least about 2.0 ng / mL at about 144 hours.

[0635] In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of not more than about 27.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of not more than about 22.5 ng / mL at about 48 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of not more than about 21.5 ng / mL at about 72 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of not more than about 21.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of not more than about 20.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 15 mg of risperidone to a human results in a plasma level of not more than about 17.0 ng / mL at about 144 hours.

[0636] In one embodiment, administration of a gastric retention dosage form comprising about 15 mg of risperidone to a human produces plasma levels of about 7.0 ng / mL to about 27.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric retention dosage form comprising about 15 mg of risperidone to a human produces plasma levels of about 6.5 ng / mL to about 22.5 ng / mL at about 48 hours. In one embodiment, administration of a gastric retention dosage form comprising about 15 mg of risperidone to a human produces plasma levels of about 4.5 ng / mL to about 21.5 ng / mL at about 72 hours. In one embodiment, administration of a gastric retention dosage form comprising about 15 mg of risperidone to a human produces plasma levels of about 3.0 ng / mL to about 21.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric retention dosage form comprising about 15 mg of risperidone to a human produces plasma levels of about 2.5 ng / mL to about 20.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric retention dosage form comprising about 15 mg of risperidone to a human produces plasma levels of about 2.0 ng / mL to about 17.0 ng / mL at about 144 hours.

[0637] In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human produces plasma levels of at least about 20.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human produces plasma levels of at least about 16.0 ng / mL at about 48 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human produces plasma levels of at least about 14.5 ng / mL at about 72 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human produces plasma levels of at least about 12.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human produces plasma levels of at least about 9.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human produces plasma levels of at least about 6.0 ng / mL at about 144 hours.

[0638] In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of no more than about 39.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of no more than about 39.0 ng / mL at about 48 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of no more than about 38.0 ng / mL at about 72 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of no more than about 35.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of no more than about 30.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of no more than about 25.0 ng / mL at about 144 hours.

[0639] In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of about 20.0 ng / mL to about 39.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of about 16.0 ng / mL to about 39.0 ng / mL at about 48 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of about 14.5 ng / mL to about 38.0 ng / mL at about 72 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of about 12.0 ng / mL to about 35.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of about 9.0 ng / mL to about 30.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric retention dosage form comprising about 30 mg of risperidone to a human results in a plasma level of about 6.0 ng / mL to about 25.0 ng / mL at about 144 hours.

[0640] In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of at least about 20.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of at least about 16.0 ng / mL at about 48 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of at least about 14.5 ng / mL at about 72 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of at least about 12.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of at least about 9.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of at least about 6.0 ng / mL at about 144 hours.

[0641] In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of no more than about 39.0 ng / mL at about 24 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of no more than about 39.0 ng / mL at about 48 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of no more than about 38.0 ng / mL at about 72 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of no more than about 35.0 ng / mL at about 96 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of no more than about 30.0 ng / mL at about 120 hours. In one embodiment, administration of a gastric-retentive dosage form comprising about 45 mg of risperidone to a human produces a plasma level of no more than about 25.0 ng / mL at about 144 hours.

[0642] In one embodiment, administration to a human of a gastric retention dosage form comprising about 45 mg of risperidone produces plasma levels of about 20.0 ng / mL to about 39.0 ng / mL at about 24 hours. In one embodiment, administration to a human of a gastric retention dosage form comprising about 45 mg of risperidone produces plasma levels of about 16.0 ng / mL to about 39.0 ng / mL at about 48 hours. In one embodiment, administration to a human of a gastric retention dosage form comprising about 45 mg of risperidone produces plasma levels of about 14.5 ng / mL to about 38.0 ng / mL at about 72 hours. In one embodiment, administration to a human of a gastric retention dosage form comprising about 45 mg of risperidone produces plasma levels of about 12.0 ng / mL to about 35.0 ng / mL at about 96 hours. In one embodiment, administration to a human of a gastric retention dosage form comprising about 45 mg of risperidone produces plasma levels of about 9.0 ng / mL to about 30.0 ng / mL at about 120 hours. In one embodiment, administration to a human of a gastric retention dosage form comprising about 45 mg of risperidone produces plasma levels of about 6.0 ng / mL to about 25.0 ng / mL at about 144 hours.

[0643] In any of these embodiments, administration of the gastric retention dosage form can be carried out at least 7 days after administration of immediate-release risperidone, such as administration of about 2 mg of immediate-release risperidone for at least about 7 days, or administration of about 4 mg of immediate-release risperidone for at least about 7 days, or administration of about 6 mg of immediate-release risperidone for at least about 7 days.

[0644] In additional embodiments, an immediate-release dosage form of risperidone can be administered to an individual for a first period, then an immediate-release dosage form of risperidone and one or more gastric retention systems comprising risperidone can be administered to the individual for a second period, and subsequently one or more gastric retention systems comprising risperidone can be administered to the individual for a third period. The first period can be between about one day and about four weeks, such as about three days to about four weeks, about one week, about two weeks, about three weeks, or about four weeks, or between any two of those periods, such as between about one day and about one week, between about one week and about two weeks, between about one week and about three weeks, or between about one week and about four weeks.

[0645] After the first period, there is a second period in which an immediate-release dosage form of risperidone and one or more gastric retention systems comprising risperidone are co-administered to the individual. The second period can be about one day, about three days, about one week, about two weeks, about three weeks, about four weeks, about five weeks, or about six weeks, or between any two of those periods, such as between about one day and about three days, between about one day and about one week, between about three days and about one week, between about one week and about two weeks, between about one week and about three weeks, between about one week and about four weeks, between about one week and about five weeks, or between one week and about six weeks.

[0646] After the second period, there is a third period during which one or more gastric retention systems are administered to the individual. The third period can vary widely, depending on the length of time the individual needs treatment. Since many mental and / or neurological disorders may require lifelong treatment, the third period can be indefinite. Alternatively, the third period can be about one week, about one month, about three months, about six months, about nine months, about one year, about two years, about three years, about five years, or about ten years, or between any two of those periods, such as between about one week and one year, about one month and one year, about three months and about six months, about three years and about one year, about one year and about two years, or about one year and about five years.

[0647] The immediate-release dosage form of risperidone administered to the individual during the first period contains from about 1 mg to about 10 mg of risperidone, such as about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, or about 10 mg, or an amount between any two of those dosages.

[0648] The immediate-release dosage form of risperidone administered to the individual during the second period contains from about 1 mg to about 10 mg of risperidone, such as about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, or about 10 mg, or an amount between any two of those dosages.

[0649] One or more gastric retention systems containing risperidone can contain from about 10 mg to about 60 mg of risperidone, such as about 10 mg of risperidone, about 15 mg of risperidone, about 20 mg of risperidone, about 25 mg of risperidone, about 30 mg of risperidone, about 35 mg of risperidone, about 40 mg of risperidone, about 45 mg of risperidone, about 50 mg of risperidone, about 55 mg of risperidone, about 60 mg of risperidone, or an amount between any two of the above amounts.

[0650] The immediate-release dosage form of risperidone can be administered to the individual once daily.

[0651] Based on the retention period of the gastric retention system, or the period for releasing sufficient drug from the gastric retention system, a gastric retention system containing risperidone can be administered to an individual regularly within a second period. In one embodiment, the gastric retention system is administered once a week within the second period. In one embodiment, the gastric retention system contains about 15 mg of risperidone and is administered once a week during the second period. In one embodiment, the gastric retention system contains about 15 mg of risperidone and is administered once a week during the second period, and immediate-release risperidone is administered at a dose of 1 mg per day during the second period. In one embodiment, the gastric retention system contains about 30 mg of risperidone and is administered once a week during the second period. In one embodiment, the gastric retention system contains about 30 mg of risperidone and is administered once a week during the second period, and immediate-release risperidone is administered at a dose of 2 mg per day during the second period. In one embodiment, the gastric retention system contains about 45 mg of risperidone and is administered once a week during the second period. In one embodiment, the gastric retention system contains about 45 mg of risperidone and is administered once a week during the second period, and immediate-release risperidone is administered at a dose of 3 mg per day during the second period.

[0652] Based on the retention period of the gastric retention system, or the period for releasing sufficient drug from the gastric retention system, a gastric retention system containing risperidone can be administered to an individual regularly within a third period. In one embodiment, the gastric retention system is administered once a week within the third period. In one embodiment, the gastric retention system contains about 15 mg of risperidone and is administered once a week during the third period. In one embodiment, the gastric retention system contains about 30 mg of risperidone and is administered once a week during the third period. In one embodiment, the gastric retention system contains about 45 mg of risperidone and is administered once a week during the third period.

[0653] In one embodiment, during the first period, immediate-release risperidone is administered at a dose of about 2 mg per day; during the second period, immediate-release risperidone is administered at a dose of about 1 mg per day, and the gastric retention system contains about 15 mg of risperidone and is administered once a week during the second period; and the gastric retention system contains about 15 mg of risperidone and is administered once a week during the third period.

[0654] In one embodiment, during the first period, immediate-release risperidone is administered at a dose of about 4 mg per day; during the second period, immediate-release risperidone is administered at a dose of about 2 mg per day, and the gastric retention system contains about 30 mg of risperidone and is administered once a week during the second period; and the gastric retention system contains about 30 mg of risperidone and is administered once a week during the third period.

[0655] In one embodiment, during a first period, immediate-release risperidone is administered at a daily dose of about 6 mg; during a second period, immediate-release risperidone is administered at a daily dose of about 3 mg, and the gastric retention system contains about 45 mg of risperidone and is administered once a week during the second period; and the gastric retention system contains about 45 mg of risperidone and is administered once a week during a third period.

[0656] In additional embodiments, risperidone can be administered to an individual by a method that includes: administering to the individual an immediate-release dosage form of risperidone and one or more gastric retention systems that contain risperidone during a co-administration period, and then administering to the individual one or more gastric retention systems that contain risperidone during a subsequent period.

[0657] The co-administration period can be about one day, about three days, about one week, about two weeks, about three weeks, about four weeks, about five weeks, or about six weeks, or between any two of those periods, such as about one day to about three days, about one day to about one week, about three days to about one week, about one week to about two weeks, about one week - about three weeks, about one week to about four weeks, about one week to about five weeks, or one week to about six weeks.

[0658] After the co-administration period, there is a subsequent period during which one or more gastric retention systems are administered to the individual. The subsequent period can vary widely depending on the individual's need for treatment. Since many mental and / or neurological disorders may require lifelong treatment, the subsequent period can be indefinite. Alternatively, the subsequent period can last about one week, about one month, about three months, about six months, about nine months, about one year, about two years, about three years, about five years, or about ten years, or between any two of those periods, such as about one week to about one year, about one month to about one year, about three months to about 6 months, about three months to about one year, about one year to about two years, or about one year to about five years.

[0659] The immediate-release dosage form of risperidone that can be administered to the individual during the co-administration period contains about 1 mg - about 10 mg of risperidone, such as about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, or about 10 mg, or an amount between any two of those doses.

[0660] One or more gastric retention systems that contain risperidone can contain about 10 mg - about 60 mg of risperidone, such as about 10 mg of risperidone, about 15 mg of risperidone, about 20 mg of risperidone, about 25 mg of risperidone, about 30 mg of risperidone, about 35 mg of risperidone, about 40 mg of risperidone, about 45 mg of risperidone, about 50 mg of risperidone, about 55 mg of risperidone, about 60 mg of risperidone, or an amount between any two of the above dosages.

[0661] The immediate-release dosage form of risperidone can be administered to an individual once daily.

[0662] Depending on the residence period of the gastric retention system, or the period for releasing sufficient drug from the gastric retention system, a gastric retention system containing risperidone can be administered to an individual regularly within the co-administration period. In one embodiment, the gastric retention system is administered once a week during the co-administration period. In one embodiment, the gastric retention system contains about 15 mg of risperidone and is administered once a week during the co-administration period. In one embodiment, the gastric retention system contains about 15 mg of risperidone and is administered once a week during the co-administration period, and immediate-release risperidone is administered at a dose of 1 mg per day during the co-administration period. In one embodiment, the gastric retention system contains about 30 mg of risperidone and is administered once a week during the co-administration period. In one embodiment, the gastric retention system contains about 30 mg of risperidone and is administered once a week during the co-administration period, and immediate-release risperidone is administered at a dose of 2 mg per day during the co-administration period. In one embodiment, the gastric retention system contains about 45 mg of risperidone and is administered once a week during the co-administration period. In one embodiment, the gastric retention system contains about 45 mg of risperidone and is administered once a week during the co-administration period, and immediate-release risperidone is administered at a dose of 3 mg per day during the co-administration period.

[0663] Depending on the residence period of the gastric retention system, or the period for releasing sufficient drug from the gastric retention system, a gastric retention system containing risperidone can be administered to an individual regularly within a subsequent period. In one embodiment, the gastric retention system is administered once a week during the subsequent period. In one embodiment, the gastric retention system contains about 15 mg of risperidone and is administered once a week during the subsequent period. In one embodiment, the gastric retention system contains about 30 mg of risperidone and is administered once a week during the subsequent period. In one embodiment, the gastric retention system contains about 45 mg of risperidone and is administered once a week during the subsequent period.

[0664] In one embodiment, immediate-release risperidone is administered at a dose of about 1 mg per day during the co-administration period, and the gastric retention system contains about 15 mg of risperidone and is administered once a week during the co-administration period, and the gastric retention system contains about 15 mg of risperidone and is administered once a week during the subsequent period.

[0665] In one embodiment, immediate-release risperidone is administered at a dose of about 2 mg per day during the co-administration period, and the gastric retention system contains about 30 mg of risperidone and is administered once a week during the co-administration period, and the gastric retention system contains about 30 mg of risperidone and is administered once a week during the subsequent period.

[0666] In one embodiment, immediate-release risperidone is administered daily in an amount of about 3 mg during a co-administration period, and the gastric retention system contains about 45 mg of risperidone and is administered once a week during the co-administration period, and the gastric retention system contains about 45 mg of risperidone and is administered once a week during a subsequent period.

[0667] Individuals to whom risperidone is administered may have a mental or neurological disorder. The mental or neurological disorder can be schizophrenia. The mental or neurological disorder can be bipolar disorder. The mental or neurological disorder can be irritability associated with autism.

[0668] Immediate-release dosage form co-administered with a gastric retention system

[0669] During any co-administration period, if an immediate-release dosage form of risperidone or a salt thereof and one or more gastric retention systems containing risperidone or a salt thereof are administered to an individual, the immediate-release dosage form can be combined with the gastric retention system to form a combined immediate-release - gastric retention system dosage form. The immediate-release dosage form can be combined with the gastric retention system in various configurations. In a first configuration, a capsule containing the gastric retention system can be externally coated with a coating containing risperidone or a salt thereof, wherein the coating containing risperidone or a salt thereof is in immediate-release form of risperidone or a salt thereof. Once the drug-coated capsule reaches the stomach, the coating containing risperidone or a salt thereof dissolves and can be absorbed. In a second configuration, immediate-release form of risperidone or a salt thereof can be placed in a capsule containing the gastric retention system, for example, in powder, gel, tablet, or any other form compatible with the container in the capsule; when the capsule dissolves in the stomach, the immediate-release form of risperidone or a salt thereof is released together with the gastric retention system. Then the immediate-release risperidone or a salt thereof can be absorbed. In a third configuration, in addition to the extended-release risperidone or a salt thereof contained in the gastric retention system, the gastric retention system can also have a layer, section, or attached portion of immediate-release risperidone or a salt thereof. When the gastric retention system is released in the stomach, the portion of immediate-release risperidone or a salt thereof dissolves and then can be absorbed.

[0670] The immediate-release dosage form of risperidone or a salt thereof administered to an individual during the co-administration period can contain from about 1 mg to about 10 mg of risperidone or a salt thereof, such as about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, or about 10 mg, or an amount between any two of those doses.

[0671] Enumerated embodiments

[0672] The following enumerated embodiments represent some aspects of the present disclosure and can be combined with any other features disclosed herein where feasible.

[0673] Embodiment 1. A gastric retention system, comprising:

[0674] Six arms attached to a central elastomer, with at least one arm containing a drug eluting segment;

[0675] Each arm includes a proximal end, a distal end, and an intermediate outer surface; wherein the proximal end of each arm is attached to the elastomeric component and projects radially from the elastomeric component, and the distal end of each arm is not attached to the central elastomeric component and is located at a greater radial distance from the central elastomeric component than the proximal end;

[0676] At least one arm containing the drug eluting segment includes:

[0677] A first inert segment;

[0678] A first disintegrating matrix segment attached to the first inert segment;

[0679] A second inert segment attached to the first disintegrating matrix segment;

[0680] A second disintegrating matrix segment attached to the second inert segment;

[0681] A third inert segment attached to the second disintegrating matrix segment;

[0682] A fourth inert segment attached to the third inert segment;

[0683] A drug eluting segment attached to the fourth inert segment, wherein the drug eluting segment contains a carrier polymer and risperidone or a salt thereof, and wherein the drug eluting segment further contains a coating that includes a polymer film for regulating the release rate;

[0684] An optional fifth inert segment attached to the drug eluting segment; and

[0685] A third disintegrating matrix segment, which is attached to the optional fifth inert segment when the optional fifth inert segment is present, or which is attached to the drug eluting segment when the optional fifth inert segment is not present; and filaments connecting each arm in a circumferential direction.

[0686] Embodiment 2. A gastric retention system, comprising:

[0687] Six arms attached to a central elastomer, with at least one arm containing a drug eluting segment;

[0688] Each arm includes a proximal end, a distal end, and an intermediate outer surface; wherein the proximal end of each arm is attached to the elastomeric component and projects radially from the elastomeric component, and the distal end of each arm is not attached to the elastomeric component and is located at a greater radial distance from the elastomeric component than the proximal end;

[0689] At least one arm containing the drug eluting segment includes:

[0690] A first inert segment;

[0691] A first disintegrating matrix section attached to the first inert section;

[0692] A second inert section attached to the first disintegrating matrix section;

[0693] A second disintegrating matrix section attached to the second inert section;

[0694] A third inert section att...

Claims

1. A method of administering risperidone or a salt thereof to an individual, comprising: administering to the individual, during a first period, an immediate-release - gastric retention system dosage form of a combination of one or more risperidone or a salt thereof; administering to the individual, during a second period, one or more gastric retention systems comprising risperidone or a salt thereof.

2. The method of claim 1, wherein the first period is from about one day to about four weeks.

3. The method of claim 1, wherein the first period is from about one week to about two weeks.

4. The method of claim 1, wherein the first period is from about one day to about one week.

5. The method of claim 1, wherein the first period is about one week.

6. The method of any one of claims 1 - 5, wherein the second period is from about one week to about one year.

7. The method of any one of claims 1 - 5, wherein the second period is from about three months to about one year.

8. The method of any one of claims 1 - 5, wherein the second period continues indefinitely.

9. The method of any one of claims 1 - 8, wherein the gastric retention system is contained within a capsule, and the capsule comprises a coating that comprises immediate-release risperidone or a salt thereof.

10. The method of any one of claims 1 - 8, wherein the gastric retention system is contained within a capsule, and the capsule further comprises an immediate-release dosage form of risperidone or a salt thereof.

11. The method of any one of claims 1 - 8, wherein the gastric retention system has a layer, section, or attachment portion of immediate-release risperidone or a salt thereof.

12. The method of any one of claims 1 - 11, wherein the immediate-release dosage form of risperidone or a salt thereof administered to the individual during the first period comprises from about 1 mg to about 10 mg of risperidone or a salt thereof.

13. The method of claim 12, wherein the immediate-release dosage form of risperidone or a salt thereof administered to the individual during the first period comprises about 2 mg, about 4 mg, or about 6 mg of risperidone or a salt thereof.

14. The method of any one of claims 1 - 13, wherein one or more gastric retention systems comprising risperidone or a salt thereof comprise from about 10 mg to about 60 mg of risperidone or a salt thereof.

15. The method of claim 14, wherein one or more gastric retention systems comprising risperidone or a salt thereof comprise about 15 mg, about 30 mg, or about 45 mg of risperidone or a salt thereof.

16. The method of any one of claims 1 - 15, wherein one or more gastric retention systems comprising risperidone or a salt thereof are administered to the individual weekly during the second period.

17. A method of administering risperidone or a salt thereof to an individual, comprising: administering to the individual, during a first period, an immediate-release dosage form of risperidone or a salt thereof; administering to the individual, during a second period, an immediate-release dosage form of risperidone or a salt thereof and one or more gastric retention systems comprising risperidone or a salt thereof; and administering to the individual, during a third period, one or more gastric retention systems comprising risperidone or a salt thereof.

18. The method of claim 17, wherein the first period is from about one day to about four weeks.

19. The method of claim 18, wherein the first period is from about one week to about two weeks.

20. The method of claim 18, wherein the first period is from about one day to about one week.

21. The method of claim 18, wherein the first period is about one week.

22. The method of any one of claims 17 - 21, wherein the second period is from about one day to about six weeks.

23. The method of claim 22, wherein the second period is from about one week to about three weeks.

24. The method of claim 22, wherein the second period is about one week.

25. The method of any one of claims 17 - 24, wherein the third period is from about one week to about one year.

26. The method of any one of claims 17 - 24, wherein the third period is from about three months to about one year.

27. The method of any one of claims 17 - 24, wherein the third period continues indefinitely.

28. The method of any one of claims 17 - 27, wherein the immediate - release dosage form of risperidone or a salt thereof administered to the individual during the first period comprises from about 1 mg to about 10 mg of risperidone or a salt thereof.

29. The method of claim 28, wherein the immediate - release dosage form of risperidone or a salt thereof administered to the individual during the first period comprises about 2 mg, about 4 mg, or about 6 mg of risperidone or a salt thereof.

30. The method of any one of claims 17 - 29, wherein the immediate - release dosage form of risperidone or a salt thereof administered to the individual during the second period comprises from about 1 mg to about 10 mg of risperidone or a salt thereof.

31. The method of claim 30, wherein the immediate - release dosage form of risperidone or a salt thereof administered to the individual during the second period comprises about 1 mg, about 2 mg, or about 3 mg of risperidone or a salt thereof.

32. The method of any one of claims 17 - 31, wherein the immediate - release dosage form of risperidone or a salt thereof is administered to the individual daily during the first period, daily during the second period, or daily during the first and second periods.

33. The method of any one of claims 17 - 32, wherein one or more gastric - retention systems comprising risperidone or a salt thereof comprise from about 10 mg to about 60 mg of risperidone or a salt thereof.

34. The method of claim 33, wherein one or more gastric - retention systems comprising risperidone or a salt thereof comprise about 15 mg, about 30 mg, or about 45 mg of risperidone or a salt thereof.

35. The method of any one of claims 17 - 34, wherein one or more gastric - retention systems comprising risperidone or a salt thereof are administered to the individual weekly during the second period, weekly during the third period, or weekly during the second and third periods.

36. The method of any one of claims 17 - 27, wherein during the first period, immediate - release risperidone or a salt thereof is administered in an amount of about 2 mg per day; during the second period, immediate - release risperidone or a salt thereof is administered in an amount of about 1 mg per day, and the gastric - retention system comprises about 15 mg of risperidone or a salt thereof and is administered once a week during the second period; and the gastric - retention system comprises about 15 mg of risperidone or a salt thereof and is administered once a week during the third period.

37. The method of any one of claims 17 - 27, wherein during the first period, immediate - release risperidone or a salt thereof is administered in an amount of about 4 mg per day; during the second period, immediate - release risperidone or a salt thereof is administered in an amount of about 2 mg per day, and the gastric - retention system comprises about 30 mg of risperidone or a salt thereof and is administered once a week during the second period; and the gastric - retention system comprises about 30 mg of risperidone or a salt thereof and is administered once a week during the third period. The method of any one of claims 17 - 27, wherein during a first period, immediate - release risperidone or a salt thereof is administered at a daily amount of about 6 mg; during a second period, immediate - release risperidone or a salt thereof is administered at a daily amount of about 3 mg, and the gastric - retention system contains about 45 mg of risperidone or a salt thereof and is administered once a week during the second period; and the gastric - retention system contains about 45 mg of risperidone or a salt thereof and is administered once a week during a third period.

39. A method of administering risperidone or a salt thereof to an individual, comprising: administering to the individual during a co - administration period a risperidone or a salt thereof and an immediate - release dosage form of one or more gastric - retention systems comprising risperidone or a salt thereof; and administering to the individual during a subsequent period one or more gastric - retention systems comprising risperidone or a salt thereof.

40. The method of claim 39, wherein the co - administration period is from about one day to about six weeks.

41. The method of claim 40, wherein the co - administration period is from about one week to about three weeks.

42. The method of claim 40, wherein the co - administration period is about one week.

43. The method of any one of claims 39 - 42, wherein the subsequent period is from about one week to about one year.

44. The method of any one of claims 39 - 42, wherein the subsequent period is from about three months to about one year.

45. The method of any one of claims 39 - 42, wherein the subsequent period continues indefinitely.

46. The method of any one of claims 39 - 45, wherein the immediate - release dosage form of risperidone or a salt thereof administered to the individual during the co - administration period contains from about 1 mg to about 10 mg of risperidone or a salt thereof.

47. The method of claim 46, wherein the immediate - release dosage form of risperidone or a salt thereof administered to the individual during the co - administration period contains about 1 mg, about 2 mg, or about 3 mg of risperidone or a salt thereof.

48. The method of any one of claims 39 - 47, wherein during the co - administration period, the immediate - release dosage form of risperidone or a salt thereof is administered to the individual daily.

49. The method of any one of claims 39 - 48, wherein one or more gastric - retention systems comprising risperidone or a salt thereof contain from about 10 mg to about 60 mg of risperidone or a salt thereof.

50. The method of claim 49, wherein one or more gastric - retention systems comprising risperidone or a salt thereof contain about 15 mg, about 30 mg, or about 45 mg of risperidone or a salt thereof.

51. The method of any one of claims 39 - 50, wherein one or more gastric - retention systems comprising risperidone or a salt thereof are administered to the individual weekly during the co - administration period, weekly during the subsequent period, or weekly during both the co - administration period and the subsequent period.

52. The method of any one of claims 39 - 45, wherein during the co - administration period, immediate - release risperidone or a salt thereof is administered at a daily amount of about 1 mg, and the gastric - retention system contains about 15 mg of risperidone or a salt thereof and is administered once a week during the co - administration period; and the gastric - retention system contains about 15 mg of risperidone or a salt thereof and is administered once a week during the subsequent period. The method according to any one of claims 39 - 45, wherein during co - administration, immediate - release risperidone or a salt thereof is administered at a daily dose of about 2 mg, and the gastric - retention system contains about 30 mg of risperidone or a salt thereof and is administered once a week during co - administration; and the gastric - retention system contains about 30 mg of risperidone or a salt thereof and is administered once a week during a subsequent period. The method according to any one of claims 39 - 45, wherein during co - administration, immediate - release risperidone or a salt thereof is administered at a daily dose of about 3 mg, and the gastric - retention system contains about 45 mg of risperidone or a salt thereof and is administered once a week during co - administration; and the gastric - retention system contains about 45 mg of risperidone or a salt thereof and is administered once a week during a subsequent period. A method of administering risperidone or a salt thereof to an individual, comprising: administering to the individual an immediate - release dosage form of risperidone or a salt thereof during a first period; and administering to the individual one or more gastric - retention systems comprising risperidone or a salt thereof during a second period. The method of claim 55, wherein the first period is from about one day to about four weeks. The method of claim 56, wherein the first period is from about one week to about two weeks. The method of claim 56, wherein the first period is from about one day to about one week. The method of claim 56, wherein the first period is about one week. The method according to any one of claims 55 - 59, wherein the second period is from about one week to about one year. The method according to any one of claims 55 - 60, wherein the second period is from about three months to about one year. The method according to any one of claims 55 - 59, wherein the second period continues indefinitely. The method according to any one of claims 55 - 62, wherein the immediate - release dosage form of risperidone or a salt thereof administered to the individual during the first period contains from about 1 mg to about 10 mg of risperidone or a salt thereof. The method of claim 63, wherein the immediate - release dosage form of risperidone or a salt thereof administered to the individual during the first period contains about 2 mg, about 4 mg, or about 6 mg of risperidone or a salt thereof. The method according to any one of claims 55 - 64, wherein an immediate - release dosage form of risperidone or a salt thereof is administered to the individual during the first period. The method according to any one of claims 55 - 65, wherein one or more gastric - retention systems comprising risperidone or a salt thereof contain from about 10 mg to about 60 mg of risperidone or a salt thereof. The method of claim 66, wherein one or more gastric - retention systems comprising risperidone or a salt thereof contain about 15 mg, about 30 mg, or about 45 mg of risperidone or a salt thereof. The method according to any one of claims 55 - 67, wherein one or more gastric - retention systems comprising risperidone or a salt thereof are administered to the individual during the second period. The method according to any one of claims 55 - 62, wherein during the first period, immediate - release risperidone or a salt thereof is administered at a daily dose of about 2 mg; and the gastric - retention system contains about 15 mg of risperidone or a salt thereof and is administered once a week during the second period.

70. The method of any one of claims 55 - 62, wherein during a first period, risperidone or a salt thereof is administered daily in an amount of about 4 mg; and the gastric retention system comprises about 30 mg of risperidone or a salt thereof and is administered once a week during a second period.

71. The method of any one of claims 55 - 62, wherein during a first period, risperidone or a salt thereof is administered daily in an amount of about 6 mg; and the gastric retention system comprises about 45 mg of risperidone or a salt thereof and is administered once a week during a second period.

72. A gastric retention system for once-weekly oral administration to a patient, comprising an extended-release formulation, the extended-release formulation comprising an amount of risperidone or a salt thereof and a carrier polymer, the extended-release formulation further comprising one or more excipients and a polymer film that regulates the release rate, wherein: a) The amount of risperidone or a salt thereof is about 15 - 45 mg, and the plasma Cmax from once - weekly oral administration of the gastric retention system (risperidone + 9 - hydroxyrisperidone) at steady state is less than or equal to about 80 ng / mL; or b) The amount of risperidone or a salt thereof is about 15 - 45 mg, and the plasma Cavg from once - weekly oral administration of the gastric retention system (risperidone + 9 - hydroxyrisperidone) at steady state is greater than or approximately equal to 15 ng / mL; or c) The amount of risperidone or a salt thereof is about 15 - 45 mg, and the plasma concentration from once - weekly oral administration of the gastric retention system (risperidone + 9 - hydroxyrisperidone) at 168 hours after administration at steady state is greater than or approximately equal to 8 ng / mL.

73. A gastric retention system for once-weekly oral administration to a patient, comprising an extended-release formulation, the extended-release formulation comprising an amount of risperidone or a salt thereof and a carrier polymer, the extended-release formulation further comprising one or more excipients and a polymer film for regulating the release rate, wherein: a) The amount of risperidone or a salt thereof is about 15 mg, and the plasma Cmax from once - weekly oral administration of the gastric retention system (risperidone + 9 - hydroxyrisperidone) at steady state is less than or equal to about 30 ng / mL; or b) The amount of risperidone or a salt thereof is about 15 mg, and the plasma Cavg from once - weekly oral administration of the gastric retention system (risperidone + 9 - hydroxyrisperidone) at steady state is greater than or approximately equal to 15 ng / mL; or c) The amount of risperidone or a salt thereof is about 15 mg, and the plasma concentration from once - weekly oral administration of the gastric retention system (risperidone + 9 - hydroxyrisperidone) at 168 hours after administration at steady state is greater than or approximately equal to 8 ng / mL.

74. A gastric retention system for once-weekly oral administration to a patient, comprising an extended-release formulation, the extended-release formulation comprising an amount of risperidone or a salt thereof and a carrier polymer, the extended-release formulation further comprising one or more excipients and a polymer film that regulates the release rate, wherein: a) The amount of risperidone or a salt thereof is about 45 mg, and the plasma Cmax from once - weekly oral administration of the gastric retention system (risperidone + 9 - hydroxyrisperidone) at steady state is less than or equal to about 80 ng / mL; or b) The amount of risperidone or a salt thereof is about 45 mg, and the plasma Cavg from once - weekly oral administration of the gastric retention system (risperidone + 9 - hydroxyrisperidone) at steady state is greater than or approximately equal to 30 ng / mL; or c) The amount of risperidone or a salt thereof is about 45 mg, and the plasma concentration from once - weekly oral administration of the gastric retention system (risperidone + 9 - hydroxyrisperidone) at 168 hours after administration at steady state is greater than or approximately equal to 20 ng / mL.

75. A gastric retention system for administration to a patient's stomach, comprising: An elastomeric component; At least one carrier polymer - active agent component comprising a carrier polymer and risperidone or a pharmaceutically acceptable salt thereof, Wherein at least one carrier polymer - active agent component comprises a polymer film that regulates the release rate, and wherein the carrier polymer - active agent component comprises an elongate member that comprises a proximal end, a distal end, and an outer surface therebetween; wherein the proximal end of the elongate member is attached to the elastomeric component and projects radially therefrom, and the distal end of the elongate member is not attached to the elastomeric component and is located at a greater radial distance from the elastomeric component than the proximal end, wherein the gastric retention system is configured to be in a compacted form suitable for oral administration or administration through a feeding tube in a container; and to be in an uncompacted form when released from the container into a patient's stomach.

76. The gastric retention system of claim 75, wherein the polymer film that regulates the release rate comprises a polyester material having one or more repeating units of the form -R1-O-C(=O)-, wherein R1 is selected from C1-C12 alkylene, ethers containing 2 to 12 carbon atoms, and polyethers containing 3 to 12 carbon atoms.

77. The gastric retention system of claim 75 or 76, wherein the polymer film that regulates the release rate is polycaprolactone.

78. The gastric retention system of claim 75 or 76, wherein the polymer film that regulates the release rate is polydioxanone.

79. The gastric retention system of any one of claims 75-78, wherein the elastomer is concave-convex, single-concave, double-concave or annular.

80. The gastric retention system of any one of claims 75-79, wherein the elastomer comprises a material selected from silicone rubber, polysiloxane, polydimethylsiloxane, silicone rubber mixed with silica, polysiloxane mixed with silica, and polydimethylsiloxane mixed with silica.

81. The gastric retention system of any one of claims 75-80, wherein the carrier polymer comprises polycaprolactone.

82. The gastric retention system of any one of claims 75-81, wherein the elongate member further comprises a disintegrating matrix.

83. The gastric retention system of any one of claims 75-82, wherein each of the plurality of carrier polymer-active agent assemblies is an arm, and one or more of the arms comprise two or more segments.

84. The gastric retention system of claim 83, wherein each of the two or more segments is attached to an adjacent segment through a junction region.

85. The gastric retention system of claim 83, wherein each of the two or more segments is directly attached to an adjacent segment without using a junction region.

86. The gastric retention system of claim 84, wherein the junction region comprises a coupling polymer or a disintegrating matrix.

87. The gastric retention system of claim 83 or 84, wherein one or more arms are attached to the central elastomer through a coupling polymer or a disintegrating matrix.

88. The gastric retention system of claim 87, wherein one or more arms attached to the central elastomer through a coupling polymer or a disintegrating matrix further comprise an intermediate portion containing an interfacial polymer.

89. The method of any one of claims 1-88, wherein the individual has a mental or neurological disorder.

90. The method of claim 89, wherein the mental or neurological disorder is schizophrenia.

91. The method of claim 89, wherein the mental or neurological disorder is bipolar disorder.

92. The method of claim 89, wherein the mental or neurological disorder is irritability associated with autism.

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