Capsule device and procuding method thereof, pharmaceutical dosage form having the capsule device and procuding method thereof, and kit having the pharmaceutical dosage form

Abstract

This invention relates to a capsule device for use on mucous membranes, particularly for the mucous membranes of the mouth, intestine, rectum, or vagina, and to a pharmaceutical dosage form using this capsule device, comprising at least one linear or strip-shaped formulation with an active pharmaceutical ingredient. The dosage form comprises first and second hemicapsule shells and a hollow cylindrical wall structure, which together determine the size of the pore for releasing the formulation. The invention also relates to a method for producing this pharmaceutical dosage form.

Description

Technical Field

[0001] This invention relates to a capsule device and a pharmaceutical dosage form for use on mucous membranes, particularly oral or gastrointestinal mucosa. The invention also relates to a method of manufacturing the capsule device and pharmaceutical dosage forms comprising the capsule device. Prior Technology

[0002] Such capsule devices are known from WO 2020 / 183005 or WO 2016 / 102067 A1. The capsule device of WO 2016 / 102067 A1 is designed to include at least one tablet, particularly film, foil or sheet formulation containing an active pharmaceutical ingredient, a release mechanism and a triggering mechanism, wherein the triggering mechanism is designed to engage at a predetermined site of action, particularly the gastrointestinal tract, rectum or vagina, to trigger the release mechanism to release the tablet formulation. According to the embodiments in Figures 8a, 8b and 8c of WO 2016 / 102067 A1, a dosage form is known to have an elongated strip-shaped formulation containing an active pharmaceutical ingredient, which can be configured in a compressed state and an elongated state. This dosage form includes a capsule comprising a hollow space for containing the compressed formulation. The capsule device has a small hole and a first end extending from the formulation. In the compressed state, the formulation can be pulled out from the hollow space to the surrounding area of ​​the capsule through the small hole, thereby changing the formulation from a compressed state to an elongated state.

[0003] It is further known in the art to apply active ingredients to local surfaces using catheters or stent-like devices, particularly in the treatment of gastrointestinal membranes and especially esophageal membranes. Another approach involves using liquid or gel-like media with relatively high viscosity. Summary of the Invention

[0004] The present invention aims to provide a capsule device that can be efficiently manufactured, a method for efficiently manufacturing the capsule device, a pharmaceutical dosage form, and a method for manufacturing the pharmaceutical dosage form, the method including the method of manufacturing the capsule device.

[0005] The problem is solved by the capsule device of claim 1 and the method of manufacturing the capsule device for a pharmaceutical dosage form of claim 10. Preferred embodiments of the invention are the subject of the appended claims.

[0006] According to the present invention, the capsule device includes a first half-capsule shell and a second half-capsule shell, which are joined by overlapping of the first half-capsule shell and the second half-capsule shell at a joint position, wherein the first half-capsule shell has a hollow cylindrical wall including an opening, and a further provided hollow cylindrical wall part overlaps with the cross-section of the opening, thereby forming an aperture of the capsule device at the joint position.

[0007] Therefore, the engagement position refers to the location where the first and second half-capsule shells are nested or slid into each other to form the capsule device. By partially pushing them into each other, the two half-capsule shells are mechanically connected and effectively stabilized. The engagement position is defined by pushing the two half-capsule shells together to a degree that allows the compressed (i.e., wound) formulation to be easily inserted into the opening of the first half-capsule shell. If necessary, the engagement position can also be defined by further pushing the two half-capsule shells together after the compressed formulation has been inserted, so that the compressed formulation no longer falls out of the opening. Alternatively, the engagement position can be defined by pushing the two half-capsule shells together, facilitating the winding of the formulation within the cavity of the capsule device. The engagement position can also be understood as the blunt abutment of the first and second half-capsules. In this case, the two half-capsule shells are held together by a connecting mechanism. This can be achieved through a band, such as tape, through grooves in the two half-capsule shells or at least partially through a mechanical clamping mechanism of a hollow cylindrical wall structure.

[0008] The hollow cylindrical wall structure can be provided in the form of a film or sheet, which can be made of the same material as one of the two hemicapsule shells. For example, the hollow cylindrical wall structure can be stamped from the outer surface of a cylinder, and the curvature of the hollow cylindrical wall structure can be matched with the curvature of the capsule device in the opening region, thus being configured to partially cover the opening like a patch. Alternatively, for example, tape can be used as a hollow cylindrical wall structure suitable for pharmaceutical dosage forms, for example, tape that degrades in the patient's body.

[0009] The first half-capsule shell, having an opening, serves as a container, allowing the pharmaceutical preparation to be easily filled through the opening or through the open end of the first half-capsule shell. The second half-capsule shell serves as a further container and can also mechanically stabilize the capsule assembly. Therefore, the pharmaceutical dosage form of the present invention has excellent mechanical stability, which is beneficial when the patient swallows the capsule. Furthermore, it can be efficiently produced according to the method of the present invention.

[0010] "Half-capsule shell" refers to a capsule device preferably composed of two parts, referred to as "half". The dimensions, for example, the size of the two halves, may differ from each other; however, in a preferred embodiment, the two halves are designed to have substantially the same dimensions, i.e., the same size. The first and / or second half-capsule shells each have hollow cylindrical walls, preferably covered by a cap, which is preferably circular in shape, particularly having a hollow hemispherical shape. In addition to the first and / or second half-capsule shells, at least one third part may be used to form the capsule device, this third part being, for example, a cylindrical or annular element. At the joint position, the first and / or second half-capsule shells can be joined to each other by a force-fit connection and / or a positive-fit connection and / or gluing or welding.

[0011] The first half-capsule shell has a hollow cylindrical wall, preferably closed at the first end and open at the second end, wherein, more preferably, the opening is completely surrounded by the material of the hollow cylindrical wall. In this way, the first half-capsule shell, especially the wall around the opening, maintains mechanical stability and provides strength to the capsule device.

[0012] As an alternative and a better option, the hollow cylindrical wall of the first hemicapsule shell is closed at the first end and open at the second end, wherein a groove extending from the second end toward the first end forms an opening. This maximizes the opening size to facilitate the assembly of the drug dosage form.

[0013] Preferably, in the engagement position, the first capsule shell is inserted into the second capsule shell. More preferably, in the engagement position, the second capsule shell is inserted into the first capsule shell.

[0014] Preferably, the cross-sectional dimensions of the opening are designed to receive a compressed formulation before the first and second capsule shells are joined. Preferably, at the joining position, the orifice defined by the opening and a hollow cylindrical wall structure has a cross-sectional dimension designed to prevent compressed formulation from passing through the orifice. The term "cross-sectional area of ​​the opening" refers to the area occupied by the opening within the wall of the first capsule shell. The term "cross-sectional area of ​​the orifice" refers to the area occupied by the orifice when it intersects with or overlaps with the hollow cylindrical wall.

[0015] In particular, the second half capsule shell may include a second opening or a second groove that overlaps with the opening or groove of the first half capsule shell at the joining position. Thus, there is greater flexibility in positioning this hollow cylindrical wall structure along the length of the capsule - the length being measured along the axis A passing through the capsule device, particularly the cylindrical axis A, to obtain a small hole.

[0016] Preferably, the size A_o of the cross-section of the small hole is a fraction f of the size A_a of the cross-section of the opening, where A_o = f * A_a, and where preferably 0.0010 < f < 0.7500, preferably 0.0100 < f < 0.5000, preferably 0.0100 < f < 0.2500, preferably 0.0500 < f < 0.15000. The area A_o is preferably suitable for pulling out a strip-shaped elongated formulation from the small hole.

[0017] Preferably, the small hole is a slit-shaped hole that is configured to permit a strip-shaped formulation to pass through the small hole when the strip-shaped formulation extends through the small hole, and the cross-section (CS) of the hole is larger than the cross-section of the strip-shaped formulation.

[0018] Preferably, the capsule device is configured to be suitable for being swallowed by a patient.

[0019] Preferably, the capsule device includes a sinker device that occupies a part of the hollow space and provides additional weight to the drug dosage form. In one embodiment, a sinker is placed in one of the half capsule shells. Preferably, the sinker is located in the second half capsule shell. Thus, the second half capsule shell includes a holding device, such as a notch, to generally position the sinker in the hollow space of the second half capsule shell so that when the capsule is inverted, the sinker remains in the hollow space of the second half capsule and does not slip out. For example, it will not slide into the first half capsule shell due to gravity, such as preventing the sinker from sliding onto the formulation. The notch can be produced by compressing the outer part of the capsule and bending the inner part.

[0020] The shape of the orifice preferably corresponds to the outer contour of the elongated dosage form in a plane perpendicular to its long axis. For example, in the case of a strip-shaped dosage form, a slit-shaped orifice is preferred, while in the case of a linear dosage form, a circular orifice can be provided. Here, the orifice essentially provides a rectangular channel cross-section, and the cross-section of a strip-shaped dosage form is also essentially rectangular. In the case of a linear dosage form, the orifice can provide a circular channel cross-section, and the cross-section of a strip-shaped dosage form can also be essentially circular. In this way, the movement of the elongated dosage form relative to the capsule device is guided by the relative position of the orifice and the capsule device, and the dosage form is stabilized while being pulled out of the capsule device.

[0021] Preferably, the orifice is a slit-shaped orifice configured to allow a strip-shaped formulation to pass through it, wherein, preferably, the cross-sectional area (CS) of the orifice is larger than the cross-sectional area of ​​the strip-shaped formulation as it passes through the orifice. Here, the cross-sectional area of ​​the orifice defines a surface, and the cross-sectional area of ​​the strip-shaped formulation is preferably measured within said surface, and most preferably located in the middle of the orifice.

[0022] When the cross-sections of the orifice and the elongated formulation are centered on a virtual axis A, which runs longitudinally through the capsule device, the distance S between the orifice surfaces defined by the elongated formulation and the capsule device can be well measured. The orifice size causing the distance S is preferably calculated using dimension a, where dimension a is the diameter or width of the orifice, and t is the diameter of a linear article or the thickness of a strip article, where a = t + 2 * S. Referring to Figure 1c, S is preferably 10 to 2000, or 20 to 1500, or 50 to 1000, or 100 to 750, or 200 to 500, or 300 to 400 micrometers (μm). S is greater than zero and preferably greater than the value of t, especially S = f * t, where f is from 1 to 20, preferably 2 to 15, and more preferably 3 to 12. The size of a is preferably chosen to be in the range of 100 to 4000, 100 to 2000, or 200 to 1500, or 300 to 1000, or 400 to 800, or 500 to 700, or 600 micrometers (μm).

[0023] In the case of strip-shaped formulations and slit-like orifices, the length c of the channel cross-section through which the formulation passes when pulled outward is greater than the width w of the strip-shaped formulation. The channel cross-section is larger than the cross-section of a slender formulation in the same plane.

[0024] Capsule devices are typically configured as containers for oral or gastrointestinal administration. In particular, capsule devices are swallowable objects, meaning their size and shape are suitable for swallowing. This size specifically relates to the geometry of the capsule.

[0025] The first half-capsule shell may further include a sliding surface configured to guide the second half-capsule shell when the first half-capsule shell and the second half-capsule shell are nested together to form the capsule device, wherein the opening of the first half-capsule shell may extend additionally into the sliding surface such that when the first half-capsule shell and the second half-capsule shell are nested together, the opening is partially covered by the second half-capsule shell.

[0026] The capsule device can have an elongated shape, meaning that its length measured along the virtual central axis A is greater than its lateral external dimension. Without considering the orifice, the capsule device can be rotationally symmetric about the central axis A.

[0027] The capsule device may have more than one hole, particularly two holes, or more than two holes.

[0028] The present invention also relates to a method of manufacturing a capsule device as defined in any of the preceding claims, comprising at least the following steps: a) providing a first half-capsule shell (11; 11') and a second half-capsule shell (12; 12') having a hollow cylindrical wall (11c; 11c') including an opening (16; 16'); b) sliding the second half-capsule shell (12; 12') and the first half-capsule shell (11; 11') to an engagement position, and providing a hollow cylindrical wall structure that overlaps with the cross-section of the opening, thereby forming a small hole (15) of the capsule device at the engagement position.

[0029] The term "sliding" refers to engaging or overlapping a first half-capsule shell into a second half-capsule shell, or vice versa, so that the two halves reach an overlapping position. This can also include locking mechanisms, such as mechanical friction of sliding surfaces comprising one or both halves, which holds the two halves together, thus eliminating the need for further manufacturing steps to join the two halves in a manner suitable for dosage form application. However, process steps preferably performed by machine may also require joining the halves in a manner suitable for application, such as by heating or by welding, especially by material bonding.

[0030] Preferably, the method of manufacturing the capsule device includes one or both of the following steps: a) providing material for forming the capsule device, particularly first and second half-capsule shells; b) creating openings, particularly rectangular openings, in the material of the first and / or second half-capsule shells.

[0031] For example, in the case of a circular opening, the first and second halves of the capsule can each have an arc-shaped opening, so that by sliding the two halves together to the joining position, a circular or elliptical shape can be formed. This is advantageous if a formulation with a circular cross-sectional area is used.

[0032] After the step of creating an opening in the material of the first half-capsule shell, the step of forming a capsule device using the material for forming a capsule device can be performed. The step of forming a capsule device using the material for forming a capsule device can also be performed before the step of creating an opening in the material of the first half-capsule device.

[0033] Openings or grooves can be created using a workpiece of a suitable shape, such as a punching tool. The material used to form the capsule device can be the workpiece. In a corresponding preferred embodiment, the workpiece can be in the shape of a cuboid, foil, hollow cylinder, capsule, or semi-capsule.

[0034] Preferably, the method includes the step of creating an opening in the hollow cylindrical wall material of the first and / or second semi-capsule shell.

[0035] In other words, before forming the actual shell shape, an opening can be created in the wall material of the first and / or second half-capsule shell; that is, the opening is created in a two-dimensional material shape that forms the shell in a further step. Alternatively, the opening is created in the half-capsule shell, meaning that the opening is created in the wall material of the first and / or second half-capsule shell after the actual shell shape has been formed; that is, the opening is created in a three-dimensional material shape that forms the shell during the molding process.

[0036] Openings can be created by cutting or ablating the capsule material using a laser. Alternatively, punching can be used to create openings through the capsule material, producing rectangular holes through shearing. However, openings can also be better formed by injection molding of a suitable material (e.g., plastic) to form the capsule device. The opening preferably has the shape of a planar curved slit. The planar nature of the curved slit offers advantages such as facilitating the passage of strip-shaped formulations through the slit in the pull direction P, thus further improving the reliability of the mechanical process of changing the formulation from a compressed to an elongated state. If an opening is formed in the capsule wall material using a punching tool, the punched material can be transported out of the capsule using a suction device, ideally integrated into the punching tool, for example, using negative pressure suction.

[0037] The capsule is preferably formed such that a formulation having an elongated shape and containing an active pharmaceutical ingredient is inserted in a compressed state into the hollow space of the capsule device, with one end of the formulation extending through a small hole, and the formulation being able to be pulled out from the small hole in the orifice cross-section (CS) of the small hole, and a space being provided between the formulation and the hollow cylindrical wall structure defining the small hole. The capsule device is preferably configured to be swallowable by a patient.

[0038] The steps of forming an opening may include at least one of the following features: ● using a milling tool, such as a planar saw blade, or by other tools to create a plate-like cutting volume, such as a cylindrical milling head that performs lateral movement; ● using a waterjet propeller that moves laterally during abrasive waterjet cutting; ● using a laser to cut or melt material from the capsule material; ● forming a hole by shearing through perforation in the semi-capsule shell material; ● forming the semi-capsule shell by injection molding with a suitable material, such as plastic.

[0039] The steps of forming a capsule device may include applying a dip molding process to produce two half-capsule shells of the capsule device, which are joined together to form a capsule, as generally described in EP0102832A2. The steps of forming a capsule device may include applying an additive manufacturing process to form a capsule from a suitable material, particularly a 3D printing process for forming a capsule from a suitable material. The steps of forming a capsule device may include injection molding into a capsule using a suitable material.

[0040] The capsule device can be a capsule comprising a hollow cylinder covered on both sides by curved cap members. The cap members can have a substantially hemispherical shape. The cap members can be manufactured as a single piece together with the cylindrical portion. The two portions of the capsule device can be joined to form the capsule device—this facilitates the assembly of dosage forms, where the formulation is first placed in one of the two portions, and then secured by joining the two portions of the capsule device. The capsule can also be shaped to have an elliptical or oval cross-section, giving it, for example, an olive shape.

[0041] In a preferred embodiment, the capsule device is configured such that the orifice is offset from the central axis A, meaning that the central axis A does not intersect the cross-section of the orifice, or that the central axis A does not intersect the center point of the cross-section of the orifice. One advantage of this embodiment is that the force acting on the capsule device wall is reduced when the formulation is pulled from the capsule device and applied to the patient, and the risk of damage to the capsule device is decreased. In the inventors' experiments, it was found that, particularly for strip-shaped formulations, unfolding the rolled-up formulation through the orifice—set off from the central axis A—is easier than when the orifice is in a central position, meaning the central axis A of the capsule device passes through the center of the orifice.

[0042] In the case of a slit-like aperture, the aperture is preferably positioned offset from the central axis A of the capsule device. The slit is preferably formed by opposing surfaces of the walls, which form the capsule device and the hollow cylindrical wall structure.

[0043] For example, the preferred shape of the slit can be achieved initially by milling the cylindrical wall of the first semi-capsule, which forms the first semi-capsule shell and / or the hollow cylindrical wall structure, such that a plate-like volume is subtracted from the wall—when the capsule shell and the cut volume are considered as three-dimensional mathematical objects. The orientation of the plate-like volume subtracted from the capsule material is characterized by the direction of the principal plane of the plate-like volume, particularly the direction relative to the virtual central axis A of the capsule device.

[0044] The hollow space inside the capsule device is defined by at least one inner wall of the capsule device, particularly the first and second half-capsule shells.

[0045] In a preferred embodiment, the capsule device is defined by at least one wall having an outer side facing the periphery of the capsule device and an inner side facing the inner side of the hollow space. Preferably, the inner side (inner surface) and the outer side (outer surface) are parallel to each other, meaning that the outer contour surface of the hollow space is similar to the outer contour surface of the capsule device. However, it is also possible and preferred that the inner surface of the capsule device is at least partially not parallel to the outer contour surface of the capsule device. This configuration allows for the definition of auxiliary structures within the capsule device that facilitate the guidance of the formulation's movement within the capsule device or other functions.

[0046] Preferably, the auxiliary structure is an inner guide wall of the capsule device for guiding the uncoiling and / or unwinding of the formulation within the capsule device. The guide wall is configured to guide the positioning of the formulation during uncoiling and / or unwinding. The guide wall may be configured parallel to the direction of movement P, thereby allowing the formulation to move toward the orifice within the capsule device. More preferably, the guide wall may be configured aligned with the orifice, for example, preferably parallel to the longitudinal direction of the orifice, i.e., parallel to the Y direction defined in Figure 1a. The guide wall may also be implemented by protrusions in the inner wall region of the capsule device, where the formulation is placed in a position that allows it to unwind through the orifice. Such protrusions in the capsule device wall, or recesses viewed from the outside of the capsule device, can be used to guide the formulation during unwinding, for example, through the internal portion, i.e., the core of the rolled-up formulation is mechanically supported by the protrusions so that it can rotate, especially during the formulation unwinding movement.

[0047] Preferably, one or more inner walls of the capsule device are configured to form guide compartments within the capsule device. The guide compartments are configured to support the formulation in its compressed state and facilitate formulation unfolding. More preferably, one or more inner walls of the capsule device are configured to form sidewalls of a rectangular hollow space that accommodates the compressed formulation.

[0048] Preferably, the capsule device includes a guide member disposed within the internal space of the capsule device to guide the movement of a linear or tablet-shaped formulation toward a small opening in the capsule device. The guide member may be part of the inner wall of the capsule device, or may be supported by or connected to a part of the inner wall of the capsule device, particularly a wall member. This guide member may, for example, be a guiding lip or guiding spout disposed on one side of the edge of the small opening, or it may be mounted around the small opening or opening.

[0049] Preferably, the capsule device may include an auxiliary structure configured to guide the coiling and / or uncoiling of linear formulations or the coiling and / or uncoiling of strip formulations, particularly through one or more rods or cylinders around which the formulation is coiled or wound. The rods or cylinders are rotatably disposed within the capsule device to facilitate uncoiling or unfolding.

[0050] In another preferred embodiment, both the capsule device and the pharmaceutical dosage form include a sinker device. The sinker device is configured to provide negative buoyancy to the capsule device. In experiments conducted by the inventors who discovered this preferred embodiment, it was found that reducing buoyancy (e.g., by increasing the mass of the capsule device) contributes to improved swallowability of the capsule device, i.e., improved reliability of the mechanical process of the formulation from a compressed state to an elongated state. In the case of strip-shaped formulations, unfolding from a compressed state, i.e., when the strip-shaped formulation is wound on a spool, to an elongated state becomes significantly easier and more efficient. For example, such a sinker device is described in WO 2020 / 183005 A1.

[0051] In another preferred embodiment of the capsule device, when the first and second hemicapsule shells are engaged at the engagement position, the cross-section of the hollow cylindrical wall structure completely overlaps with the opening of the first hemicapsule shell. In this case, the hollow cylindrical wall structure includes a perforation and the formulation partially extends through the perforation of the hollow cylindrical wall structure.

[0052] In another preferred embodiment of the capsule device, when the first and second hemicapsule shells are engaged at the engagement position, the hollow cylindrical wall structure completely overlaps with the cross-section of the opening of the first hemicapsule shell and the cross-section of the other opening of the second hemicapsule shell. In this case, the hollow cylindrical wall structure includes a small hole, and the formulation partially extends through the small hole of the hollow cylindrical wall structure.

[0053] In another preferred embodiment of the capsule device, when the first and second capsule shells are engaged at the mating position, the hollow cylindrical wall structure completely overlaps with the cross-section of the opening of the first capsule shell and optionally the cross-section of another opening of the second capsule shell, wherein the hollow cylindrical wall structure further secures the two halves together to form the capsule device. For example, the hollow cylindrical wall structure is glued to the first capsule shell and optionally also glued to the second capsule shell, thereby mechanically securing the two halves together.

[0054] In another preferred embodiment of the capsule device, the hollow cylindrical wall structure is made of a flexible and / or elastic material and includes a small hole. In this case, the material properties of the hollow cylindrical wall structure are selected such that the formulation is not obstructed by the edges of the capsule device wall during unfolding from the capsule device. Optionally, the material properties of the hollow cylindrical wall portion are selected to support a seal inside the capsule, such as moisture protection. Further optionally, the size of the small hole in the hollow cylindrical wall structure is designed such that, due to the elastic material properties of the hollow cylindrical wall structure, the small hole can conform to the contour of the formulation and thereby further support the seal of the capsule device. When the formulation is pulled out, the pressure applied to the small hole expands or widens the small hole, so that the formulation can exit the capsule device through the small hole when the capsule device is swallowed by the patient.

[0055] The present invention also relates to a pharmaceutical dosage form comprising a capsule device as defined herein, and further comprising a pharmaceutical preparation having an elongated shape, comprising one or more active pharmaceutical ingredients, and capable of being configured in a compressed state and an elongated state.

[0056] The present invention also relates to a method for preparing a pharmaceutical dosage form, wherein the method includes the steps of preparing a capsule device, and the following further steps: a) providing a formulation having an elongated shape and comprising one or more active pharmaceutical ingredients; b) providing a first and a second half-capsule shell having a hollow cylindrical wall with an opening; c) preferably containing the formulation in a compressed state, with the formulation entering the first half-capsule shell through the opening such that a portion or one end of the formulation extends through the opening; d) sliding the second half-capsule shell (12; 12') and the first half-capsule shell (11; 11') to a mating position, and providing a hollow cylindrical wall structure overlapping the cross-section of the opening, thereby forming a small hole (15) of the capsule device at the mating position.

[0057] Preferably, the method includes the following steps: after step a) or b) of the method for preparing the drug dosage form, providing a rotating shaft (X), and preferably, placing it in front of or within the cross-section of the opening, and winding the formulation in its elongated state by rotating the rotating shaft, thereby preferably using the opening to guide and / or align the formulation until the formulation reaches a wound and compressed state. This reduces or eliminates any problems related to formulation loosening before reaching the inside of the capsule, because this compressed state is formed within and around the opening of the first semi-capsule device.

[0058] Better still, the method for preparing a drug dosage form includes the following steps: after step b) or c) of the method for preparing the drug dosage form, placing a settling device within at least a portion of the hollow space of the first and / or second semi-capsule shell, the settling device providing additional weight to the drug dosage form. This particularly facilitates the swallowing of the drug dosage form.

[0059] Ideally, any process step, particularly loading the compressed formulation into the first capsule shell, is performed automatically by machine to better produce multiple drug dosage forms simultaneously. This increases the yield per period of producing large quantities of drug dosage forms.

[0060] The step of placing or containing a formulation having an elongated shape and containing an active pharmaceutical ingredient in a compressed state within the hollow space of a capsule device, and allowing one end of the formulation to extend through a small hole, includes: the small hole and the formulation being configured such that when the formulation is pulled out of the small hole, a gap is provided between the formulation and the surface of the capsule device defining the small hole in the cross-sectional area (CS) of the small hole.

[0061] The placement of the formulation is preferably achieved by placing the formulation in the first portion or first half-capsule shell, and preferably by subsequently allowing the end of the formulation to extend through a small hole and connecting the second portion or second half-capsule shell to the first portion or first half-capsule shell. The first portion or first half-capsule shell or the second portion or second half-capsule shell can be a tubular element or a capped tubular element, or it can be a cylindrical segment, particularly a semi-cylindrical element.

[0062] The present invention also relates to a kit comprising a pharmaceutical dosage form as described in claim 13, a drinking cup, and an applicator for administering the pharmaceutical dosage form to a patient, wherein the applicator and the drinking cup are in a fluid connection and the applicator includes the pharmaceutical dosage form, wherein the formulation of the pharmaceutical dosage form is connected to the applicator through a retainer for removing the formulation from the capsule device after administration to the patient.

[0063] The capsule device and pharmaceutical dosage form containing a pharmaceutical preparation according to the invention are particularly suitable for mucous membranes, especially buccal or gastrointestinal mucosa, particularly the mucosa within the upper gastrointestinal tract, such as the pharynx, esophagus, cardia, and / or stomach. Pharmaceutical dosage forms containing pharmaceutical preparations and their applications are described in WO2016 / 102067, which is incorporated herein by reference in its entirety, particularly concerning the shape, size, and (chemical) composition of the capsule device and pharmaceutical preparation, the active pharmaceutical ingredient, and the treatment and prevention of certain conditions and diseases disclosed therein. In other words, the chemical composition of the capsule device and the pharmaceutical preparation itself have been described, at least to a large extent, in the aforementioned reference. This also applies to capsules.

[0064] The pharmaceutical dosage form of the present invention advantageously allows for improved bioavailability of the active pharmaceutical ingredient at the predetermined site of action.

[0065] The pharmaceutical dosage forms of the present invention are capable of and suitable for rapidly releasing linear or strip-shaped, particularly tablet, film, foil, or flake-shaped, pharmaceutical preparations containing active ingredients to a predetermined site of action and exerting a systemic effect. Furthermore, the pharmaceutical dosage forms according to the present invention can apply active pharmaceutical ingredients with poor bioavailability that cannot be administered orally to a predetermined site of action.

[0066] A linear or strip-shaped formulation, particularly a film, foil, or sheet, containing an active pharmaceutical ingredient, may comprise a multilayered monolayer or multilayer structure. In the case of a multilayered structure, the first layer may contain a first active pharmaceutical ingredient, and the second / additional layer may contain at least one additional active pharmaceutical ingredient. This allows for applications, for example, with two incompatible pharmaceutical ingredients.

[0067] Preferably, the formulation is made into a mucosal adhesive to allow for targeted release of the active ingredient. This can be achieved by providing a monolayer formulation that, in addition to containing the active pharmaceutical ingredient, also has mucosal adhesiveness, or by providing a multilayer formulation in which at least one layer, preferably the outermost layer, has mucosal adhesiveness.

[0068] According to a preferred embodiment, the pharmaceutical dosage form according to the invention is suitable for oral administration.

[0069] The capsule device is composed, or primarily, of a material that is inherently insoluble in a fluid present in the pathway leading to the administration site, particularly the gastrointestinal tract. Such materials are known in the art and described in WO2016 / 102067. Of particular note are known anti-gastric acid polymers, such as polymethyl methacrylate (Eudragit), HPMCAS, shellac, gelatin, etc., which can be formulated with additives known to improve processing properties, such as plasticizers, flavorings, and tasters.

[0070] This formulation contains at least one active pharmaceutical ingredient selected from the following (the drug name also includes any pharmaceutically acceptable salt thereof): diagnostic substances, such as dyes or stains; analgesics, preferably NSAIDs, such as ibuprofen or flurbiprofen; antibiotics, such as penicillin, amoxicillin, or vancomycin; preservatives, such as 2,4-dichlorobenzyl alcohol, amylmetacresol, or cetylpyridinium chloride; steroids such as corticosteroids, glucocorticoids, fluticasone, budesonide, clocortolone, perdesonide, hydrocortisone, clobetasonbutyrate, flumetason, flupredniden, hydrocortisone aceponate, and hydrocortisone butyrate. buteprate, hydrocortisone-17-butyrate, triamcinolon acetonid, amcinoid, betamethasone-17,21-dipropionate, betamethasone-17-valerate, methylphenidate, dexamethasone, diflucortolon-21-valerate, fluocinolon acetonid, fluocinonid, fluticason-17-propionate, methylprednisolone aceponate, mometasone furoate, pednicarbat, or clobetasol-17-propionate;Parasitic agents, also known as antiparasitic drugs, include mebendazole, albendazole, tiabendazole, diethylcarbamazine, diaminodiphenyl sulfone, benznidazole, ivermectin, pyrantel, and praziquantel; antifungal agents include nystatin, imidazole, thiazole, thiazole, clotrimazole, ketoconazole, and undecylenic acid; crystal violet (hexamethyl pararosaniline chloride), amphotericin B, and botulinum toxin. Toxin), sucralfate, nitric oxide or nitric oxide-forming agents such as isosorbide dinitrate or nitroglycerin, furanocoumarins, benzoic acid, citric acid, lactic acid, pH buffers, antacids, calcium carbonate, magnesium carbonate, or aluminum carbonate.

[0071] Alternatively or additionally, the formulation may contain an anti-inflammatory agent, such as montelukast, an interleukin receptor, or an interleukin antibody. Additionally or additionally, the tablet formulation may contain beclomethasone dipropionate, budesonide, or ciclesonide, which are particularly beneficial for the treatment of asthma. Additionally or additionally, the tablet formulation may contain mesalazine, sulfasalazine, or olsalazine, which are particularly beneficial for the treatment of inflammatory bowel disease.

[0072] The active pharmaceutical ingredient contained in the tablet formulation of the pharmaceutical dosage form according to the present invention can be particularly selected from proteins and peptides, especially insulin, buserelin, desmopressin, calcitonin, and estrogens, as well as biotechnologically manufactured drugs, such as antibodies, such as rituximab. It should be understood that proteins and peptides, especially insulin, buserelin, desmopressin, calcitonin, and estrogens, may exhibit poor bioavailability in certain situations—especially poor oral bioavailability—and are therefore good candidates for application according to the dosage form method of the present invention.

[0073] The following substances may also be used as active pharmaceutical ingredients: drugs acting on bones and muscles, drugs acting on the nervous system, hormones and drugs acting on the hormonal system, gynecological drugs, drugs acting on the cardiovascular system, drugs acting on the respiratory system, drugs acting on the gastrointestinal tract, diuretics, drugs acting on sensory organs, dermatological drugs, vitamins and micronutrients, peptides and proteins, analgesics, anti-infectives and antiparasitics.

[0074] In one embodiment, the active ingredient is selected from corticosteroids. Examples include budesonide, mometasone, fluticasone, and ciclesonide, and their pharmaceutically acceptable salts.

[0075] As for the conditions to be treated, such as those related to the gastrointestinal mucosa, with priority given to the esophagus, such as GERD, NERD, and eosinophilic esophagitis, they are particularly suitable for treatment with the aforementioned steroids and the nitric oxide or nitric oxide-forming agents.

[0076] Pharmaceutical formulations contain a certain amount of active pharmaceutical ingredient, the amount of which depends on the known effective amount for treating the condition, as well as the site of administration and the active ingredient. For example, compared to formulations containing mometasone, budesonide has a significantly higher concentration / amount in the formulation.

[0077] Alternatively, in some embodiments of the capsule device according to the invention, the linear or strip-shaped formulation is adapted to dissolve, for example, biodegradable, preferably in a time-controlled manner, for example, within one hour, or one to two hours, or one to five hours, or one to twelve hours, or one to twenty-four hours. This improves user convenience because there is no need to remove the tablet-shaped formulation.

[0078] There are no particular limitations on the methods for preparing formulations containing these active ingredients, and these methods are known to those skilled in the art. Similarly, reference can be made to WO2016 / 102067 regarding the pharmaceutical dosage forms of this invention.

[0079] Those skilled in the art can prepare formulations, particularly linear or strip-shaped ones, by methods generally known, such as coating an inert carrier containing a polymer, active pharmaceutical ingredient, and optional additives and solvents, using a method involving, for example, a doctor blade, spray processor, or extrusion processor. The resulting film layer is then dried. For multilayer sheet formulations, one or more coatings can be applied to an existing film layer in the same manner, or they can be manufactured separately and subsequently laminated.

[0080] The shape of the orifice preferably corresponds to the outline of the elongated formulation in a plane perpendicular to its long axis. For example, in the case of a strip-shaped formulation, a slit-shaped orifice is preferable, while in the case of a linear formulation, a circular orifice can be provided. Here, the orifice essentially provides a rectangular channel cross-section, and the cross-section of a strip-shaped formulation is also essentially rectangular. In the case of a linear formulation, the orifice can provide a circular channel cross-section, and the cross-section of a strip-shaped formulation can also be essentially circular. Thus, the movement of the elongated formulation relative to the capsule device is guided by the relative position of the orifice and the capsule device, and the formulation is stabilized while being pulled out of the capsule device.

[0081] Preferably, linear or strip-shaped articles are flexible, allowing them to be transformed from a compressed form to an elongated form, particularly folded, rolled, coiled, or rolled-up sheet formulations, which can better achieve a linear, rope-like, strip-like, or tubular shape. For example, such sheet formulations are described exemplified in WO 2020 / 183005 below.

[0082] In a preferred embodiment of the capsule device, in order to pull the formulation contained in the capsule from the hollow space of the capsule into the surrounding area of ​​the capsule device, the formulation can expand from a compressed state to an elongated state. Therefore, the formulation preferably includes a holding device. After securing the holding device, the formulation can be pulled out of the capsule device by pulling and / or applying force. Preferably, the holding device is secured by connecting it to a retainer. This retainer can be a cord-like component, such as a rope, thread, or cord. Then, for example, the retainer prevents the holding device from moving with the capsule device, thereby generating a pulling force. For example, this is achieved by connecting the holding device to one end of a cord, the other end of which is secured in the delivery device. Thus, when the cord of the retainer is tightened by removing the capsule from the delivery device, the holding device generates a pulling force, causing the formulation to be pulled out of the capsule device. Since the holding device is preferably part of or attached to the formulation, the holding device can be a handle, a strap, or a tape, or may include an adhesive area. A gripping device is suitable for establishing and maintaining a connection that can transmit force between the gripping device and its attachment area. Furthermore, this connection can be established or maintained when the dosage form and / or the tablet formulation is in its compressed and / or elongated form. Preferably, the gripping device can hold itself and possibly other parts in a defined position or area through force engagement, particularly by friction, form engagement, or by material bonding, especially by mucosal adhesion, preferably by adhesives. For example, such a holding device is described in WO 2016 / 102067 A1.

[0083] As used herein, the term "compressed form" tends to refer to a folded form, a coiled form, a rolled-up form, a curled form, or a folded form. Specifically, compared to a non-compressed form, especially an elongated form, a linear or strip-shaped article in a compressed form has a smaller spatial extent and / or less exposed surface. More preferably, a linear or strip-shaped article in a compressed form is folded, rolled up, coiled, wound, compressed, aggregated, or otherwise formed into a smaller form. Specifically, a linear or strip-shaped article in a compressed form has a predetermined size or spatial extent.

[0084] As used herein, the term "elongated form" tends to refer to an unfolded form, a spread-out form, an open form, an elongated form, a stretched form, or a rectangular form. In particular, compared to non-elongated forms, especially compressed forms, linear or strip-shaped articles have a larger spatial extent and / or more exposed surface area in an elongated form. Preferably, linear or strip-shaped articles in an elongated form are unfolded, spread out, opened, laid out, untied, lengthened, stretched, opened, or formed into a larger format in another manner. In particular, linear or strip-shaped articles have a predetermined size or spatial extent in an expanded form. Alternatively, the size or spatial extent of a linear or strip-shaped formulation may depend on the conditions of presence and the site of action or application, and therefore may not be predetermined.

[0085] In a particularly preferred embodiment, the formulation is wound around the outside of the capsule device. In this case, for example, the aim is to place the formulation in its compressed form within a first half-capsule shell and then connect a second half-capsule shell to the first half-capsule shell only subsequently to form the capsule device, wherein a hollow cylindrical wall structure is provided to form a perforation in the capsule device.

[0086] However, the formulation can be wound inside the capsule device in an alternative manner. If wound inside the capsule device, it is advantageous to provide the formulation in an elongated state from the outside, and to supply the formulation into the capsule device, for example, during winding, through an opening and / or aperture. In this case, the capsule device preferably has a first half-capsule shell having a hollow cylindrical wall including an opening, and the wall of a second half-capsule shell optionally overlaps the cross-section of the opening. After the formulation is wound inside the capsule device, a wall structure is provided to cover the opening of the first half, and this wall structure is placed on the first half-capsule shell and optionally the second half-capsule shell to form the aperture of the capsule device.

[0087] Preferably, the winding of the formulation is performed by a machine, such as a winding device or unit. Alternatively, the formulation can be wound manually. During manual and machine winding of the formulation, for example, the end portion of the formulation is clamped between two gripping jaws, or if a substantially continuous formulation is used, a portion of the formulation is clamped and the portion outside the clamped portion is cut off, so that the clamped portion of the formulation forms one end of the formulation to be wound. As a further example, the clamped portion of the formulation is woven into the forked or U-shaped end of a winding pin, thereby winding the formulation onto one end of the pin by rotating the pin. Subsequently, for example, the pin surrounding the formulation is placed through an opening in a capsule device, and the pin is pulled out from the surrounding formulation. In a particularly preferred embodiment, the coiled formulation is placed through an opening in a first semi-capsule shell.

[0088] Alternatively, the formulation, in its elongated state, is fed into a pressing chamber via a conveyor, such as a conveyor belt. Multiple surfaces, preferably rotating in a common direction, are arranged inside the pressing chamber, causing the drawn-in but undisturbed formulation to rotate. Furthermore, the rotational motion of the formulation can be supported by rollers. The principle is similar to that of a baler. The rotational motion of the rotating surfaces within the pressing chamber is transmitted to the formulation, causing the formulation itself to enter a rotational motion and thus begin winding. Once the formulation has reached a predetermined size and / or weight, the rotational motion stops, and the wound formulation is discharged from the pressing chamber and, for example, directly into the opening of a capsule device.

[0089] Machines used for winding formulations into a compressed form have a balance, allowing the determination of the amount of active ingredient contained in the formulation by measuring the weight during winding or by measuring the weight of the portion of formulation used for winding. Alternatively, a device can be used to measure the length, width, or thickness of the portion of formulation to be wound, or any combination of these quantities (e.g., volume). In other alternatives, it must be possible to determine the concentration of the active ingredient in the compressed form of the formulation.

[0090] The present invention also relates to a production machine for producing pharmaceutical dosage forms according to the invention, particularly by performing the method according to the invention, the production machine including a positioning device for placing a first semi-capsule shell in an installation position.

[0091] A connecting device having a movable element configured to move a first and a second capsule shell toward each other to connect a second capsule shell and a first capsule shell to an engagement position, such that the wall of the second capsule shell optionally overlaps with the cross-section of the opening, the extent of the overlap being controlled by the amount of movement of the movable element at the engagement position.

[0092] Preferably, the positioning device includes one or more holding members for holding one or more first and / or second capsule shells in place. The holding members preferably include retaining spaces, which are shaped to engage with the first and / or second capsule shells via form-fitting connections. The positioning device, particularly the holding members, can be configured to hold multiple first and / or second capsule shells in parallel positions. This increases the throughput of the production method. The positioning device can be used to position one or more first and / or second capsule shells in more than one mounting location. In this way, several steps in the production of the pharmaceutical dosage form can be performed using multiple mounting locations, particularly at workstations simultaneously.

[0093] The positioning device preferably includes a movable platform that carries one or more workstations. Preferably, each workstation includes at least one or more clamping members. The movable platform is rotatably mounted on a base member that is rotatable about an axis and is configured to rotate each workstation to a working position on the production machine. In a first working position, a feeding device may be provided for feeding at least one first half-capsule shell into at least one mounting position provided by at least one clamping member. In a second working position, a feeding device may be provided for feeding at least one second half-capsule shell into at least one mounting position provided by at least one clamping member. In a third working position, an assembly device may be provided for assembling the formulation into the first half-capsule shell, preferably in a compressed state. This assembly device may include a transport device for transporting at least a portion or all of the formulation to the mounting position and / or a compression device, particularly a winding device, for changing the formulation from an elongated state to a compressed state, particularly a folded or wound state. In a fourth working position, a receiving station may be provided to receive the drug dosage form to be manufactured and may transfer it to a storage or conveying system.

[0094] Preferably, the production machine includes a conveying device for conveying one end of a formulation having an elongated shape and containing an active pharmaceutical ingredient from a formulation storage location to an installation location, where the formulation is positioned for insertion, particularly through an opening, into the hollow space of a first semi-capsule shell, which is in the installation position. In a preferred embodiment, the conveying device has a rotatable conveying member configured to receive at least a portion or the entire formulation in a first position, particularly from a formulation storage device, and to convey said at least a portion to the installation location by rotation. The rotatable conveying member can be a rotatable bar member or a disk member. The movement or rotation of the conveying device can be controlled by an electronic control unit of the production machine. The production machine and / or the rotatable conveying member includes a winding device for winding the formulation from its elongated state to its compacting condition. The rotatable conveying member may include a winding device for winding the formulation in its elongated state to form an entangled state. The winding device may include one, two, or more rotatable shafts configured to be electrically driven and controlled by the electronic control unit of the production machine. One, two, or more rotatable shafts may be positioned offset from the axis of rotation of the rotatable conveyor member. The rotatable conveyor member and / or the winding device may be configured to wind an elongated formulation in an installed position, particularly if the rotatable shaft is positioned in front of or within an opening, so that the formation of the compressed formulation occurs in a compressed position, preferably in front of or even within the opening, and therefore preferably, at least a portion of which is directly within the hollow space of the first semi-capsule shell, in which case the first semi-capsule shell is in the installed position. This significantly facilitates the transfer of the formulation into the capsule. The winding of the formulation is preferably performed using a winding pin. Therefore, the winding device preferably includes a winding pin.

[0095] Preferably, the production machine and / or conveying device includes a compression device, particularly a winding device for winding the formulation from its elongated state to its compressed state, or a folding device for folding the formulation from its elongated state to its compressed state. This compression action is preferably performed at the compression position of the production machine.

[0096] Preferably, the production machine includes a cutting device for cutting the formulation to form the formulation, which will be inserted into the hollow space of the first semi-capsule shell.

[0097] Preferably, the production machine includes an actuation device for moving the compressed formulation from the compressed position to its terminal position within the hollow space of the first semi-capsule shell.

[0098] Preferably, the production machine also includes a pressing device for pressing the precipitated tablet material, such as powder, to obtain precipitated tablet units. The pressing device is preferably configured to supply the obtained precipitated tablet units to further preparation equipment for producing this pharmaceutical dosage form.

[0099] In one embodiment, the applicator of the swallowing-aid capsule device, combined with a drinking cup, can be used for drug administration. Such an applicator is described, for example, in WO2020 / 183003A1. This is particularly advantageous if the dosage form is to be administered periodically, especially daily, because drug administration via the capsule device can be performed without professional assistance.

[0100] The applicator includes a housing and a capsule holder configured to receive a capsule device. The applicator preferably also includes a spacer. In one embodiment, the applicator is not directly attached to the opening of the drinking cup. Instead, the spacer is located between the drinking cup and the applicator. The spacer thus reduces the risk that moisture in the drinking cup before use may render the dosage form unusable. For example, residual moisture from the drinking cup may enter the applicator. This spacer is preferably tubular or annular and can be screwed onto the openings of the applicator and drinking cup, respectively, after the respective caps have been removed. The spacer preferably has a length of 1 to 10 mm, more preferably 2 to 8 mm, and most preferably 5 mm.

[0101] The present invention also relates to a retainer. The retainer is part of the drug delivery device, as the drug delivery device also includes a retainer. In a preferred embodiment, the retainer consists of or includes a thread element. The retainer is wound around a capsule holder. The capsule holder thus includes a wall structure. The retainer is preferably attached to or secured to the capsule holder such that it can transmit forces (e.g., mechanical traction) to the capsule holder and thus to the drug delivery device. The retainer preferably comprises or is composed of yarn, fiber, cord, or thread having a first end and a second end. The retainer is connected at its first end to one end of the formulation, for example, to a gripping device of the formulation extending through a small opening in the capsule device. The second end of the retainer is connected to the capsule holder of the drug delivery device, for example, to the wall structure of the capsule holder. Because the retainer is connected to the formulation, when the capsule is removed from the drug delivery device and the retainer is tightened, the retainer detaches from the capsule holder. When the patient swallows the capsule, the capsule is removed from the capsule holder, thereby detaching the retainer from the capsule holder. When a patient swallows the capsule, the retainer will at some point completely detach from the capsule handle and generate tensile stress, pulling the formulation out of the capsule. Thus, the retainer, such as a linear member, powerfully allows the release of the active pharmaceutical ingredient, particularly into the mucosa surrounding relatively small lumens or cavities (such as the esophagus or nasal cavity).

[0102] Before using the applicator, wrap the retainer around the wall structure of the holder. Wrapping the retainer around the holder prevents it from tangling inside. When the patient swallows the dosage form, the retainer is unwound from the holder.

[0103] The retainer is wound around the structure of the grip and / or bonded to the formulation, for example, attached to a cord containing the formulation, or attached to a holding device for the formulation, preferably by means of a machine, such as by means of a winding and / or bonding machine, particularly in the bonding area of ​​the machine.

[0104] In the first step, the retainer is mechanically secured in the machine, for example, by a support claw. In the second step, the retainer is tightened. In the third step, the handle is positioned under a mechanical clutch along the tensioned retainer, and the retainer is clamped into a groove in the wall structure of the handle. In the fourth step, the support claw holding the retainer is released. In the fifth step, the handle is rotated by rotating the clutch that secures and supports the handle, thereby winding the retainer around the handle. This coupled rotational motion is superimposed on a vertical translational motion, so the retainer is wound around the handle in a positional overlapping manner. In the sixth step, the support claw secures the retainer again, and in the seventh step, a blade-like part of the machine cuts through one end of the retainer, which is connected to the formulation in a further step. In the eighth step, particularly mechanically, the handle with the retainer wound around it is positioned above an opening in the drug delivery device housing, preferably with the opening pushed upward on an axis, such as an auxiliary tube, that passes through the housing located within the machine. Furthermore, the cut end of the retainer is placed at one end of the formulation and can then be pulled out of the capsule. In the ninth step, the retainer is bonded to one end of the formulation in the clamp bonding area. The retainer can be wound around the handle by rotating it about a winding axis as described, or alternatively, the retainer can be rotated around a fixed handle to wind the retainer.

[0105] In a preferred embodiment of the applicator, the cap of the applicator, which covers the applicator opening and is removed before use to allow the medication to leave the applicator body, includes a lid and a plurality of springs configured to press a support element on the capsule, preferably in contact with one end of the capsule within a handle, preferably facing the lid. For example, the lid is similar to that of an affervescent tablet.

[0106] Therefore, in a preferred embodiment, the capsule is placed vertically within the handle, and a support element presses against the end of the capsule facing the cap. The cap preferably further contains a desiccant to prevent moisture from rendering the dosage form unusable, for example, during its shelf life. Multiple springs, which can be made of plastic or any elastic material, apply pressure to the support element, mechanically securing the capsule in the handle by pushing the support element against the surface of the capsule. The support element preferably has a shape complementary to the contour of the capsule, such that the capsule contour fits into the support element.

[0107] In a preferred embodiment, the pharmaceutical dosage form includes a capsule device and a settling tablet. The capsule device contains a pharmaceutical preparation for application to a mucosa, preferably the esophageal mucosa. The preparation is connected to a retainer of the applicator, which is configured to pull out the preparation upon swallowing the dosage form. The retainer dissolves in the oral cavity after a period of time, and the preparation adheres to the mucosa, particularly the esophageal mucosa. The settling tablet and capsule device dissolve in the stomach.

[0108] In a preferred embodiment, a drug dosage form is manufactured according to the following process steps, attached to a retainer, and packaged into a delivery device: In a first step, the capsule device is inserted into a machine via an inserting case. The capsule device includes a first and a second half-capsule shell joined by overlapping a first and a second half-capsule shell at a mating position.

[0109] In the second step, the second capsule shell is clamped by the insert box and separated from the first capsule shell. Additionally, the applicator housing is located on the machine.

[0110] In the third step, the first capsule shell moves toward the perforating tool via the piston, causing the insertion pin of the perforating tool to enter the cavity of the first capsule shell, particularly the cylindrical cavity. The insertion pin thus grips the first capsule shell, causing the perforating tool to move laterally relative to the direction of movement of the insertion pin, creating an opening and / or groove through the wall of the first capsule.

[0111] In the fourth step, the insertion pin is pulled out of the cavity of the first half-capsule shell. The first half-capsule shell is positioned so that the opening is preferably aligned with the outer shell of the delivery device. The piercing tool uses negative pressure to transport the material pierced from the capsule wall out of the first half-capsule shell.

[0112] In the fifth step, the formulation is clamped between two holding jaws and slightly stretched by increasing the distance between the jaws. On one side of one of the holding jaws, the portion of the formulation extending beyond that jaw is cut off flush with the jaw, thus creating a cut end of the formulation while it remains stretched. This cut end of the formulation serves as the starting point for winding the formulation. Therefore, a winding mandrel is threaded onto the stretched formulation between the two jaws. Since the end of the formulation is now also held by the winding mandrel, one of the jaws used for cutting is released. After or during the release of the jaw, the winding mandrel rotates so that the cut end of the formulation held by the jaws is wound onto the winding mandrel, thus creating the first winding.

[0113] In the sixth step, release one of the two grippers and begin rotating the winding mandrel. During this process, additional formulation is wound around the rotating mandrel. Once a predetermined length of formulation has been wound, stop rotating the mandrel. Ideally, the length should be such that one end of the formulation is not wound, i.e., the formulation is not completely wound. This end of the formulation is used to connect the formulation to the retainer, i.e., to one end of the retainer.

[0114] In the seventh step, the formulation wound on the winding mandrel is placed in front of the pre-drilled opening in the first half-capsule shell. The wound formulation may also partially extend into the pre-drilled opening or groove. The unwound end of the formulation remains outside the first half-capsule shell.

[0115] In the eighth step, the winding mandrel is pulled out of the wound formulation and the wound formulation is mechanically pushed through the opening into the first semi-capsule, thereby placing the wound formulation inside the first semi-capsule shell.

[0116] In the ninth step, the insertion pin moves into the special hollow cylindrical opening of the first half-capsule shell, thereby positioning the wound formulation placed inside the first half-capsule shell in step eight deeper within the first half-capsule shell. The unwound formulation end portion is positioned on the adhesive area of ​​the machine.

[0117] In step ten, the retainer is configured to wrap around the holder of the delivery device. Step ten can also be performed simultaneously with other production steps, either earlier or later. To wrap the retainer around the holder, it is mechanically secured in the machine via a clamp and cut unit. The clamp and cut unit includes jaws that grip and tighten the retainer. It also includes cutters for cutting the retainer and a guiding block to ensure a smooth cut. In step ten, the retainer is tightened by moving the jaws.

[0118] In step eleven, the grip is positioned on the winding unit and placed along the tensioned retainer, which is attached to the grip's wall structure. Because the retainer is attached to the grip, it winds around the grip as the grip rotates.

[0119] In the twelfth step, one of the jaws of the clamping and cutting unit is released, allowing the retainer to slide across the jaws in a guided manner for winding. The unit also includes another jaw containing the tool, which remains closed.

[0120] In the thirteenth step, the winding unit begins to rotate, for example, by rotating the clutch that secures and supports the grip, thereby winding the retainer around the grip. Ideally, the rotational motion is superimposed with the vertical translational motion, causing the retainer to alternately overlap and wrap around the grip.

[0121] In step fourteen, after the retainer of a predetermined length is wound around the handle, the grippers of the winding unit further clamp the retainer so that the retainer remains held by the grippers of the winding unit while the cutter of the clamping and cutting unit cuts the retainer. The cutter then cuts the retainer. However, the retainer is not cut directly at the grippers of the winding unit, but rather away from the unit. Therefore, a small portion of the retainer remains outside the grippers of the winding unit after cutting. This short portion of the retainer is used to attach the retainer to the formulation in further process steps. The winding unit also includes a robot gripper.

[0122] In step fifteen, the robotic gripper of the winding unit transfers the handle, wrapped with the retainer, and a section of the retainer held by the grippers of the winding unit to the machine section containing the first half-capsule shell, which is also the location of the administration device housing. The robotic gripper positions the handle on the shaft by pushing it into the shaft located within the housing. In doing so, the handle is only pushed a certain length onto the shaft, allowing the shorter portion of the retainer (which is used to attach the retainer to the formulation) to be placed on the bonding area located outside the housing. The bonding area also includes the end of the formulation extending through the opening of the first half-capsule shell, i.e., through the small hole of the capsule device when the two halves are joined at the bonding position, and this small hole is formed by a hollow cylindrical wall structure.

[0123] In step sixteen, the retainer and / or formulation is preferably wetted through an atomizer nozzle. Humidification is performed on the bonded area.

[0124] In step seventeen, the retainer is pressed onto the formulation through an impression to attach the formulation to the retainer. This connection allows tensile force to be transferred between the retainer and the formulation.

[0125] In step eighteen, a settling tablet is produced and inserted into the second capsule shell. Step eighteen can also be performed simultaneously with other production steps, or earlier or later. The settling tablet is preferably formed by pressing powder using a pressing pin. A robotic rotary arm can move into the powder, draw in a predetermined amount of powder, and press the powder. The robotic rotary arm then removes the powder and rotates onto the second capsule shell, wherein the pressed powder is preferably inserted directly into the second capsule shell as sediment. The step of producing the settling tablet can be performed independently of other processing steps, i.e., the settling tablet can be produced earlier or simultaneously with further processing steps, and the robotic arm can simply grasp the pressed or otherwise manufactured settling tablet. The capsule device may also be without a settling tablet, thus step eighteen can also be omitted.

[0126] In step nineteen, a second capsule shell, with and / or without a settling tablet, is placed above the first capsule shell via an inserting case. After the two capsule shells are stacked, the second capsule shell is pressed onto or into the first capsule shell via the inserting case, thus forming a mating position. The unwound formulation end extends into the mating area and is connected to the end of the retainer.

[0127] In the twentieth step, the aperture is formed by adding a hollow cylindrical wall structure to the first half-capsule shell, which is connected to the second half-capsule shell at the joint. Alternatively, the aperture can be formed by simultaneously adding a hollow cylindrical wall structure to both the first and second half-capsule shells, so that the hollow cylindrical wall structure covers both half-capsule shells to form the aperture. This has the advantage that the two half-capsule shells are additionally secured together by the hollow cylindrical wall structure, thereby mechanically stabilizing the capsule device.

[0128] In step 21, the capsule device of the drug dosage form formed in step 20 is clamped and positioned above the handle with a clamping tool, and then placed in the handle.

[0129] In step twenty-two, push the outer casing onto the handle. Place one end cap onto the outer casing. This closes the outer casing, which now contains a retainer wrapped around the handle and a drug dosage form placed in the handle, with the end of the retainer connected to the end of the dosage form so that when the retainer is fully extended, for example, when the patient swallows the dosage form, the retainer can pull out the dosage form.

[0130] Further preferred embodiments of the method for producing pharmaceutical dosage forms of the present invention and further preferred embodiments of the method for producing pharmaceutical dosage forms of capsule devices of the present invention can be obtained from the description of the present invention and its embodiments, and from the description of the embodiments with reference to the accompanying drawings.

[0131] Exemplary embodiments of the invention will now be described in more detail with reference to the accompanying drawings and examples, from which further features, advantages and embodiments can be understood. Simple Explanation of the Diagram

[0132] Figure 1a illustrates a schematic side view of a dosage form according to a first embodiment of the present invention.

[0133] Figure 1b illustrates the details of the area marked "X" in Figure 1a.

[0134] Figure 1c shows another morphological diagram of the area marked "X" in Figure 1a.

[0135] Figure 2a illustrates a top view of the first and second half-capsule shells, which, according to another preferred embodiment of the invention, are aligned with each other to form a capsule device of a pharmaceutical dosage form.

[0136] Figure 2b illustrates a top view of the first and second semi-capsule shells, which, according to another preferred embodiment of the invention, are aligned with each other to form a capsule device of a pharmaceutical dosage form.

[0137] Figure 2c shows a top view of the first and second half-capsule shells of Figure 2a, which are glued together along the direction of movement M.

[0138] Figure 2d shows a top view of the capsule device formed by the joining position of the first and second half-capsule shells in Figure 2a, where the second half-capsule shell is shown as transparent, representing the area where the opening of the second half-capsule shell wall partially overlaps.

[0139] Figure 2e corresponds to Figure 2d, in which the first semi-capsule shell has a hollow cylindrical wall structure that overlaps with the first capsule shell wall shown as the diagonal area, thereby forming a small hole.

[0140] Figure 3a is a side view of the situation in Figure 2a.

[0141] Figure 3b illustrates the insertion of a compressed pharmaceutical preparation into the opening of a first semi-capsule device, forming an exemplary step in the method for preparing a pharmaceutical dosage form according to the present invention.

[0142] Figure 3c illustrates another exemplary step in the method of preparing a drug dosage form according to the present invention, where a compressed form of the drug is inserted into the hollow space of the first semi-capsule device.

[0143] Figure 3d illustrates a pharmaceutical dosage form using the capsule device of Figure 2d according to an embodiment of the present invention.

[0144] Figure 4a illustrates first and second semi-capsule shells for a pharmaceutical formulation, and a rotating shaft X located within the opening, the rotating shaft having a strip-shaped formulation attached thereto, forming an exemplary step in the method for producing a pharmaceutical dosage form according to the present invention.

[0145] Figure 4b illustrates first and second semi-capsule shells for a pharmaceutical formulation according to Figure 3d, including a rotating shaft X located within an opening and a strip-shaped formulation (R) partially wound around the shaft, forming an exemplary step in the method of producing a pharmaceutical dosage form in this invention.

[0146] Figure 4c illustrates first and second semi-capsule shells for a pharmaceutical formulation as shown in Figure 3d, including a rotating shaft X located within an opening and a strip-shaped formulation (R) completely wound around the shaft, forming an exemplary step of the method for producing a pharmaceutical dosage form in this invention.

[0147] Figure 4d illustrates a second half-capsule shell for a pharmaceutical formulation as shown in Figure 3d, including a sinker element inserted into the hollow space of the second half-capsule shell, forming an exemplary step in the method of producing a pharmaceutical dosage form in this invention.

[0148] Figure 5a illustrates the first step of using this kit to facilitate drug delivery before the patient swallows the drug dosage form.

[0149] Figure 5b illustrates the second step of using this kit to facilitate drug delivery after the patient has swallowed the medication.

[0150] Figure 6a is about this kit and illustrates the steps for attaching the retainer to the grip wall structure.

[0151] Figure 6b is about this kit and illustrates the steps of wrapping the retainer around the handle of the delivery device after the retainer is attached to the wall structure of the handle.

[0152] Figure 6c describes the kit and illustrates the steps for attaching the retainer to the formulation grip.

[0153] Figure 6d is about this kit and illustrates the steps of joining the first half-capsule shell to the second half-capsule shell, while the retainer is connected to the formulation.

[0154] Figure 6e is about this kit and illustrates the steps of assembling the capsule device with the delivery device when the retainer is connected to the formulation.

[0155] Figure 7 illustrates the formulation end connected to the retainer of the delivery device.

[0156] Figure 8 exemplarily illustrates a production machine for producing the pharmaceutical dosage form of the present invention, particularly by implementing the method according to the present invention.

[0157] Figure 9a illustrates, exemplarily, the mounting device of a production machine for dispensing a formulation into a first semicapsule shell in a first step, wherein an elongated formulation is wound at the mounting position.

[0158] Figure 9b illustrates, exemplarily, the apparatus of Figure 9a in the second step, wherein the elongated formulation is easily rolled up and immediately cut by the cutting device.

[0159] Figure 9c illustrates, exemplarily, the installation apparatus of Figure 9b in the third step, in which the elongated formulation is easily rolled up, cut from the storage roll, and pushed by an actuating device into the hollow space of the first semi-capsule shell through the opening.

[0160] Figure 10a illustrates a schematic cross-section of the applicator, in which a drug dosage form is disposed at the bottom of the applicator holder and covered by the applicator cap.

[0161] Figure 10b illustrates a schematic cross-section of a drug delivery device containing a drug dosage form and featuring a modified delivery device cover.

[0162] Figure 11a illustrates a top view of the first and second half-capsules aligned with each other at the joint position and having a hollow cylindrical wall structure, thereby forming a capsule device of a pharmaceutical dosage form according to another preferred embodiment of the present invention.

[0163] Figure 11b illustrates a top view of the first and second half-capsules aligned with each other at the joint position and having a hollow cylindrical wall structure, thereby forming a capsule device of a pharmaceutical dosage form according to another preferred embodiment of the present invention. Implementation

[0164] Figure 1a shows a capsule device 1 for application to mucous membranes, comprising a formulation 2 having an elongated shape and containing an active pharmaceutical ingredient. Formulation 2 is shown in a compressed state: assuming the formulation has a strip-like shape, Figure 1a shows the strip-like formulation wound in a spiral shape in a virtual axis side view, the virtual axis being perpendicular to the drawing page. In an elongated state, when the formulation is pulled out from the slit-like opening 5 of the capsule 3, the strip-like formulation will have a generally straight, elongated shape.

[0165] The capsule device 3 has the shape of a capsule and includes a hollow space 4, which contains the formulation 2 in a compressed state. The capsule consists of a thin wall with a thickness of approximately 50 μm to 200 μm and is made of biodegradable or non-biodegradable material.

[0166] The capsule device has a small aperture 5 shaped as a planar curved slit. The width 'a' of this aperture 5 can be defined by measuring the distance between two opposing surfaces in a direction parallel to the length axis A. These two surfaces are surface 5a of the first semi-capsule shell 3a and surface 8a of the hollow cylindrical wall structure. For example, the distance 'a' can be a constant value between 200 μm and 600 μm. For example, the thickness 't' of the formulation can be a constant value between 20 μm and 150 μm.

[0167] Regarding the external dimensions of the capsule device, for example, the height H of capsule 3 could be 8 mm, and the width W of capsule could be 4 mm. However, other dimensions of the capsule device are often possible, taking into account the patient's desired administration site.

[0168] In the compressed state of the formulation, the first end 2a of formulation 2 extends through the orifice 5 to allow the formulation to be grasped from the hollow space and pulled out into the surrounding area of ​​the capsule device, thereby changing the formulation 2 from a compressed state to an elongated state. Pulling out the formulation, i.e., the pull-out motion P (see Figure 1b), can be the result of fixing the end 2a of the formulation and pulling the capsule device 3 in the opposite direction M to P. As in this example, the process of administering the capsule device involves swallowing the capsule device and connecting the end 2a of the formulation to the holder of a delivery device including a drinking cup, as shown in Figures 5a and 5b.

[0169] The first end 2a may have an end portion (see Figure 1c) that has a different shape from the strip 2. For example, the end portion may form a sealing portion adapted to be placed at the orifice 5, which can be used to seal the orifice before the end portion is pulled out of the orifice. The end portion may also be configured to provide a connecting area for connection to a retainer of the delivery device.

[0170] Figure 1b shows an enlarged view of the orifice region 5. The orifice 5 is created by a hollow cylindrical wall structure 8, as shown in Figures 1a, 1b, and 1c, which is attached to the first semi-capsule shell 3a, thus overlapping the opening 6 of the first semi-capsule shell 3a to form a slit-like orifice 5. The dimensions of the slit-like orifice 5 and the strip-shaped formulation 2 are defined such that, when the formulation is pulled out of the orifice, a gap (S1; S2) is provided on the cross-section CS of the orifice 5, between the formulation 2 and the capsule device surface 5a (S2) and the hollow cylindrical wall structure 8a (S1), thereby defining the orifice 5. Here, the central length axis A of the capsule extends parallel to the orifice cross-section CS. In the embodiment shown in Figure 1, the surface of the capsule wall 5a is associated with the second semi-capsule shell 3b. However, a hollow cylindrical wall structure 8 can also be placed to connect to the second half-capsule shell 3b to a certain extent, and accordingly, a spacing (S1; S2) is provided, measured on the cross-section CS of the aperture 5, between the surface 5a (S2) of the formulation 2 and the first half-capsule shell of the capsule device and the surface (S1) of the hollow cylindrical wall structure 8a, thereby defining the aperture 5. The capsule device 3, as shown in Figure 1a, includes a first half-capsule shell 3a and a second half-capsule shell 3b, wherein the first half-capsule shell 3a and the second half-capsule shell 3b are partially nested to form the capsule device 3, or, in another manner, the first and second half-capsule shells can be aligned with each other but not nested. When partially nested, the opening 6 of the first half-capsule shell 3a can be partially covered by the second half-capsule shell 3b. In one embodiment, the opening is formed as a groove in the first half-capsule shell, and if the first half-capsule shells are partially nested in the engagement position, the second half-capsule shell partially overlaps the groove. In one embodiment, the opening is formed, for example, a hole in the wall of the first semi-capsule shell, then the second semi-capsule shell may or may not overlap with the opening of the first semi-capsule shell. Such an opening 6 can be created by milling the capsule material using a plate-shaped milling tool, such as a plate saw blade. In the embodiments shown in Figures 1a, 1b, and 1c, the overlap position, i.e., the joint position between the two semi-capsule shells 3a and 3b, is indicated by the dashed line marked B.

[0171] As shown in Figure 1b, the thickness t of the strip 2 is significantly smaller than the width a of the planar curved slit 5. For example, the thickness t can be a constant value between 20 μm and 150 μm. The spacing S = S1 = S2 is measured by positioning the formulation 2 at the center of the orifice 5 and at a centrally aligned position on the strip surface, which is parallel to and faces the surface 5a of the capsule and the surface 8a of the hollow cylindrical wall structure. The spacing S exists as the formulation 2 is pulled out of the orifice and can be generally constant on average, meaning approximately along the entire length of the elongated formulation. However, the scope of the invention can also cover embodiments of various dosage forms in which the spacing between the formulation and the surface 5a defining the orifice varies with the different thicknesses t of the formulation 2, or the spacing is broken in some cases—due to partial variations in dimensions a and t, including a portion of the dimension where a = t.

[0172] In the case of a formulation with a linear shape, the dimensions can be measured similarly, and in the case of an irregularly shaped formulation, the dimensions can be determined by taking an average.

[0173] As shown in Figure 1c, the first end 2a may have an end forming an enlarged portion. This configuration prevents the formulation from falling into the capsule 3, which would require the patient or user to pull out the strip and administer the dosage form in a different manner than intended to restore end 2a. End 2a may also be configured at the orifice 5 to seal the orifice 5 before end 2a is pulled out. A portion 7 may be provided at the end for connecting a thread (e.g., a holder for a drug delivery device) to end 2a. The width a' of the orifice 5 perpendicular to axis A (which indicates the elongated direction of capsule 3) can be obtained by measuring the distance between the opposing surfaces 5a' of the second half-capsule shell. The dimension of width a' may be similar to the width of the formulation end 2a.

[0174] Figure 2a shows a top view of a first semi-capsule shell 11 and a second semi-capsule shell 12, aligned with each other to form a capsule device 13 of a pharmaceutical dosage form 10 according to another preferred embodiment of the invention. The first semi-capsule shell 11 has a first end closed by a spheroid cap 11a and a second end, which is a hollow cylindrical wall 11b providing an opening for the first semi-capsule shell 11. The second semi-capsule shell 12 has a first end closed by a spheroid cap 12a and a second end, which is a hollow cylindrical wall 12b providing an opening for the second semi-capsule shell 12. The first semi-capsule shell 11 has a hollow cylindrical wall 11c completely surrounding an opening 16, which is essentially a hole in the wall 11c. Stability is provided by a wall frame 11c surrounding the opening 16.

[0175] Figure 2b shows a top view of a first semi-capsule shell 11' and a second semi-capsule shell 12', aligned with each other to form a capsule device for a pharmaceutical dosage form according to another preferred embodiment of the invention. The first semi-capsule shell 11' has a first end closed by a spherical cap 11a' and a second end, which is a hollow cylindrical wall 11b' providing an opening for the first semi-capsule shell 11'. The second semi-capsule shell 12' has a first end closed by a spherical cap 12a' and a second end, which is a hollow cylindrical wall 12b' providing an opening for the second semi-capsule shell 12'. The hollow cylindrical wall portion 11c' does not completely surround the opening, which in particular forms a groove 16' extending from the wall edge of the second end 11b' towards the first end 11a'. The groove provides sufficient space for processing the formulation, particularly for inserting a compressed formulation 2 into the hollow space of the first semi-capsule shell 11' in a direction perpendicular to the plane of the figure and / or along direction M.

[0176] Figure 2c shows a top view of the first and second half-capsule shells of Figure 2a, which are joined together by sliding adhesion along the direction of movement M, i.e., nesting together. The cylindrical portion of the second half-capsule shell 12 may have a diameter slightly larger than that of the cylindrical portion of the first half-capsule shell 11 to facilitate engagement of the first half-capsule shell 11 and the second half-capsule shell 12. The two half-capsule shells 3a and 3b are pushed into each other to a degree such that the formulation 2 can be effortlessly inserted into the opening 6 of the first half-capsule shell 3a in its compressed (i.e., coiled) form, which subsequently defines the engagement position. If necessary, the engagement position can also be defined by further pushing the two half-capsule shells 3a and 3b together after the formulation 2 has been inserted in its compressed form, so that the formulation 2 will not fall out of the opening 6.

[0177] Figure 2d shows a top view of the capsule device 13 formed by the joining position of the first half-capsule shell 11 and the second half-capsule shell 12 in Figure 2a. As shown in Figure 2d, the second half-capsule shell is shown as transparent to illustrate that region 12c of the wall 12b of the second half-capsule shell overlaps with the opening 16. As indicated by the arrows, the opening 16, which remains open at the joining position, is partially covered by the hollow cylindrical wall structure 17 to form a small hole 15. The small hole 15 is a slit that extends circumferentially and tangentially around axis A within the capsule wall. The cross-section A_o of the small hole is significantly smaller than the cross-section A_a of the opening 16, for example, by multiplying by a coefficient f = 0.05 to 0.2: A_o = f * A_a. In this way, the formulation can be easily inserted into the opening 16 at the disassembly position of the first half-capsule shell 11 and the second half-capsule shell 12, and will not fall out of the small hole 15 in its compressed state. When swallowed, it can be easily pulled out through the slender position of the small hole 15 when it is unwound from the entangled state (see Figure 5b).

[0178] Figure 2e corresponds to Figure 2d, in which the first semi-capsule shell has a hollow cylindrical wall structure that overlaps with the area of ​​the first semi-capsule shell wall marked by a horizontal diagonal line, thereby forming a small hole 15.

[0179] Figure 3a is a side view of the situation in Figure 2a. The opening 16 has a rectangular shape when projected onto the plane, but is cylindrical in the circumferential direction, following the shape of 11b. It is essentially open almost along the cylinder to its full width W (see Figure 1b), allowing the formulation in a compressed state to be inserted through the opening 16 into the hollow space 14 of the capsule device or the first semi-capsule shell in a direction perpendicular to axis A (see Figure 3b).

[0180] Figure 3b shows a compressed form of the pharmaceutical preparation inserted into the opening 16 of the first semi-capsule shell 11.

[0181] Figure 3c shows a compressed form of drug formulation fully inserted into the hollow space 14 of the first semi-capsule shell 11, with the compressed form of formulation end 2a extending through the opening 16, and even the second semi-capsule shell 12 moving to engage with the first semi-capsule shell 11, thereby continuously reducing the free cross-section of the opening 16 until the engagement position is reached.

[0182] Figure 3d shows a drug dosage form 10 using the capsule device shown in Figure 2d. A transparent, hollow cylindrical wall structure 17 partially covers the opening 16, forming a small hole.

[0183] Figure 4a shows a first half-capsule shell 11 and a second half-capsule shell 12 for a pharmaceutical formulation, and shows a rotating shaft X located within an opening 16, with a strip-shaped formulation 2 connected to the shaft X, forming an exemplary step of the method according to the invention for producing capsule devices and assembling pharmaceutical dosage forms.

[0184] Figure 4b shows a first half-capsule shell 11 and a second half-capsule shell 12 of a pharmaceutical formulation according to Figure 3d, including an axis X of rotation R, the axis being located within—or in front of—the opening—and having a strip-shaped formulation 2 wound around the axis through the rotation (R) portion, forming an exemplary step of the method according to the invention for producing capsule devices and assembling pharmaceutical dosage forms. The direction of rotation (R) in Figure 4b is chosen as an example, and can therefore also be opposite to the direction of rotation (R) shown.

[0185] Figure 4c shows a first half-capsule shell 11 and a second half-capsule shell 12 of a pharmaceutical formulation according to Figure 3d, including a rotating shaft X located within an opening and having a strip-shaped formulation (R) completely wound around the shaft by rotation, forming an exemplary step of the method according to the invention, which is used to produce capsule devices and assemble pharmaceutical dosage forms.

[0186] Figure 4d shows the second half-capsule shell of the pharmaceutical formulation according to Figure 3d, including a settling element 60 inserted into the hollow space of the second half-capsule shell 12, forming an exemplary step of the method according to the invention for producing capsule devices and assembling pharmaceutical dosage forms.

[0187] Figure 5a shows a patient administering a drug dosage form comprising the capsule device described herein. A drinking cup 901 is filled with liquid and a delivery device 902 is attached to the cup 901. The delivery device 902 includes a drug dosage form comprising a capsule device 903 and a retainer 904 connected to the dosage form, which is included in the capsule device 903.

[0188] Figure 5b illustrates the process when a patient swallows the capsule device 903 and its transport through the esophagus to the stomach. A retainer 904 pulls the formulation 905 out of the capsule device 903. The formulation 905 then spreads along the esophagus, thus delivering the active ingredient of the formulation 905 to the esophageal mucosa.

[0189] Figure 6a illustrates a method of wrapping a retainer 101 around a handle 102 of a delivery device using a machine 100. Thus, as shown in Figure 6a, in the first step of wrapping the retainer 101 around the handle 102, the retainer 101 is mechanically secured in the machine 100, which includes a clamping and cutting unit 110. The cutting unit 110 includes a jaw 106, a cutter 108, and a guide 107. In the second step, the retainer 101 is tightened by moving the jaw 106. In the third step, the handle 102 is positioned along the tensioned retainer 101, and a mechanical clutch 109 clamps the retainer 101 into a groove in the wall structure of the handle 102.

[0190] Figure 6b illustrates a method of wrapping a retainer around the handle of a drug delivery device after the retainer has been attached to the wall structure of the handle. In a first step, as shown in Figure 6b, the gripper 106 for holding the retainer 101 opens. In a second step, the handle 102 is rotated in a winding unit, for example by a clutch 109 that rotates to hold and support the handle 102, thereby wrapping the retainer 101 around the handle 102. A vertical translational motion is superimposed on the rotational motion, such that the retainer 101 is wrapped around the handle 102 in a positional overlapping manner, and after the retainer is fully wrapped around the handle 102, in a sixth step, the gripper again secures the retainer 101. In a third step, a blade-like component 108 of the machine 100 cuts off one end of the retainer 101, which is then attached to the formulation in a subsequent further step.

[0191] Figure 6c illustrates a method of connecting a retainer to the holder of a formulation, meaning connecting the retainer 101 to the formulation while further assembling the assembly using a machine. In a first step, specifically using a machine, a handle 102, around which the retainer 101 is wound, is positioned above an opening 110 of the applicator housing 111. Thus, the handle 102 and the opening 110 are pushed upwards by a shaft 112 (e.g., an auxiliary tube). The shaft 112 thus passes through the housing 111, which is already placed in the machine 100. Further positioned in the machine 100 and disposed beside the applicator housing 111 is a first half-capsule shell 105a of the capsule device, such that at least a portion of the formulation extends from the first half 105a onto the engagement region 113 of the machine 100. Further disposed within the engagement region 113 of the machine 100 is a cut end 101a of the retainer 101. The cut end 101a is then pulled out of the capsule device 103 from the formulation.

[0192] Figure 6d illustrates a method for joining the first and second half-capsule shells, while a retainer is attached to the formulation. As shown in the first step, the retainer end 101a is joined to one end of the formulation in a clamping engagement region 113. A support 114 moves downward toward the engagement region 113 and presses against the overlapping formulation and retainer end 101a. The joining is further described in Figure 10. In the second step, the second half-capsule shell 105b is positioned above the first half 105a together with the settling tablet element 115. In the third machine step, the two halves 105a, 105b are overlaid, joined, or slid into each other, such that the opening is closed to form the engagement position of the capsule device. In the fourth step, a hollow cylindrical wall structure is attached to the capsule device, thereby forming a small hole. The hollow cylindrical wall structure can be attached only to the first half-capsule shell or to both the first and second half-capsule shells, thus overlapping both halves simultaneously. The end of the formulation can be pulled out of the capsule device from the small hole of the capsule device by the retainer 101.

[0193] Figure 6e relates to a method of assembling the capsule device with the delivery device, while the retainer is connected to the formulation. Therefore, Figure 6e shows the steps of assembling the drug dosage form (i.e., the capsule device, which includes the formulation and, in the case shown, the sedimentation tablet element 115) with the delivery device. Thus, in the first step, a clamping element 116 holding the capsule device 103 under negative pressure is positioned above the capsule device 103 to clamp and transport the capsule device 103 above the delivery device housing 111. In the second step, the capsule device 103 is placed inside the housing 111. The housing 111 further includes a retainer 101, which wraps around the handle 102 and is located within the opening 110 of the housing 111, as described in the previous steps relating to Figures 6c and 6d. In the third step, the delivery device housing 111 is covered by an end cap 117.

[0194] Figure 7 shows the end 701 of the formulation connected to a retainer 702, for example, one end of the retainer. To connect the retainer 702 to the end 701 of the formulation, in a first step, the retainer is immersed in an aqua pure solution. In this embodiment, water acts as an adhesive. However, other embodiments are also conceivable in which substances other than water can be used as adhesives.

[0195] The retainer is preferably immersed in the solution for 1 to 10 seconds, or 1 to 5 seconds, or about 1 second. In the second step, the immersed retainer 702 is placed on the water-wetted end 701. Thus, the retainer 702 overlaps the formulation end 701 by a distance d, the overlap distance d being in the range of 0.5 to 2 cm, or 0.5 to 1.5 cm, or 0.5 to 1 cm, or preferably 1 cm. After positioning the retainer 702, it is pressed onto the formulation end 701, while the end 701 remains wetted. The pressing time is preferably 1 to 10 seconds, or 1 to 5 seconds, or 2 to 3 seconds. Pressing is performed using a contact pressure stamp. In a further third step, before further processing of the joint, the joined retainer 702-formulation 701 is dried for 1 to 10 minutes, or 2 to 8 minutes, or preferably 5 minutes. Alternatively, the retainer 702 may be placed dry on the end 701 without being immersed, such that the retainer 702 overlaps the end 701 of the formulation by a distance d, and the retainer and the end 701 are sprayed with aqua pure before pressing. Spraying can be performed using a nozzle, such as a spray nozzle or an atomizer nozzle, to atomize the liquid onto the surface to be sprayed. Using a nozzle facilitates the dispersion of the liquid into a spray. Therefore, the nozzle distributes the liquid over an area that includes at least the overlap distance d, increasing the liquid surface area and generating an impact force on the solid surface.

[0196] Figure 8 exemplarily illustrates a production machine according to the invention for producing pharmaceutical dosage forms according to the invention, particularly by performing the method according to the invention. The production machine 200 is configured for producing pharmaceutical dosage forms according to the invention, particularly by performing the method according to the invention. The production machine includes a positioning device 240 for positioning a first half-capsule shell in an installation position. A connecting device 260 has a movable element 261 configured to connect a second half-capsule shell and a first half-capsule shell to an engagement position by moving the first 11;11' and the second 12;12' half-capsule shells toward each other such that the wall 12c of the second half-capsule shell overlaps with the cross-section of the opening 16;16', the amount of overlap being controlled by the movement of the movable element 261, thereby forming a capsule device 3;13 at the engagement position. Preferably, the connecting device 260 further supports attaching a hollow cylindrical wall structure to the engaged capsule device 3;13 to form a small hole. However, additional mounting units may also be provided to attach the hollow cylindrical wall structure to the first half-capsule shell or to both the first and second half-capsule shells.

[0197] The positioning device 240 includes four holding members 243.1, 243.2, 243.3, and 243.4 for securing one or more first and / or second capsule shells in position. The holding members provide retaining space, shaped to form-fit with and retain the first and / or second capsule shells. The positioning device 240 and the holding members can be configured to hold multiple first and / or second capsule shells in parallel positions, with only one capsule produced at each mounting position. This increases the throughput of the production method. The positioning device 240 positions four first and four second capsule shells in four mounting positions, each provided by the holding members 243.1, 243.2, 243.3, and 243.4. Therefore, several steps in the production of the pharmaceutical dosage form can be performed simultaneously using multiple mounting positions, particularly at workstations defined by the holding members.

[0198] The positioning device 240 includes a rotatable platform 241 that carries workstations. Each workstation includes a clamping member located along the outer edge region of the rotatable platform. The movable platform 241 is rotatably configured at a base member (not shown) that rotates about an axis 242, configured to rotate each workstation to a working position on the production machine. In a first working position (clamping member 243.1 as shown in Figure 11), a feeding device 251 is provided for feeding at least one first semi-capsule shell 11; 11' to the mounting position provided by the holding member 243.1. In a second working position (clamping member 243.2 as shown in Figure 11), a feeding device 252 is provided for feeding a second semi-capsule shell 12; 12' to the mounting position provided by the holding member 243.2.

[0199] In the third working position (clamping member 243.3 as shown in Figure 8), an equipment device can be configured to mount the first semi-capsule shell 11; 11', so that it carries the formulation 2, preferably in a compressed state. The equipment device 201 includes a transport device 220 for transporting one end 212a; 2a of the formulation to the mounting position, and includes a clamping device 223.1; 223.2, particularly a winding device, for changing the formulation 212; 2 from an elongated state to a compressed state, particularly a folded or wound state.

[0200] In the fourth working position (clamping member 243.4 as shown in Figure 8), a receiving station 270 can be provided to receive the drug dosage form 10 to be manufactured and may transfer it to a storage or transport system (not shown).

[0201] In each case, the production machine preferably includes an electronic control unit 280 for controlling each action, which is automatically performed by the production machine, particularly by controlling the activity and parameters of at least one drive that drives the rotation of the positioning device about axis 242, the capsule feeding of devices 252 and 251, the formulation transport of the transport device, the movement of the pressing device, particularly the rotation of the winding device, the cutting movement of the cutting device, the actuation of the actuating device, the connecting movement of the connecting device 260, and any other device. The electronic control unit 280 may include a user interface for allowing a user to control the production machine, and / or control software for controlling the production machine, particularly a computer program designed to implement each step of the method according to the invention, including all possible and preferred steps described herein.

[0202] This production machine includes a formulation storage device 210, which provides a formulation storage reel 212. The formulation can be released by rotation of the reel 212 about an axis 211, thereby moving the elongated formulation toward the cutting device 230 and toward the clamping member 243.3, which provides a working position. The movement of the elongated formulation 212 is guided by a guide unit 213, which also includes a reel 214. The position 212a of the formulation 212 (which subsequently forms the first end 2a of the elongated formulation 2) is clamped by a rotating shaft 223.1, which moves to an installation position at the holding member 243.3 by rotation of a rotating disk 222 about an axis R1. See Figure 9a.

[0203] Figure 9a exemplarily shows a mounting device 201 of a production machine 200 for mounting a first semi-capsule shell 11;11' to carry the formulation 2, wherein in a first step, the elongated formulation 212 is wound at the mounting position of the retaining member 243.3.

[0204] The production machine 200 includes conveying the end 212a of a formulation having an elongated shape and containing an active pharmaceutical ingredient from a formulation storage location to an installation location, where the formulation is positioned to insert into the hollow space 14 of a first semi-capsule shell 11; 11', located at an installation location 243.3, specifically through an opening 16. Here, the conveying device has a rotatable conveying member 222 configured to receive at least a portion 212a of the formulation 212 at a first location 223.2, particularly after release from the formulation storage device 210, and to transport at least a portion 212a of the formulation to the installation location 243.3 by rotation R1. The movement or rotation of the conveying device 222 can be controlled by an electronic control unit 280 of the production machine 200.

[0205] The rotatable conveyor 222 may include winding devices 223.1; 223.2 for winding the elongated formulation to form a wound state. The winding devices have two rotatable shafts 223.1; 223.2, configured to be electrically driven and controlled by an electronic control unit 280 of the production machine. The two rotatable shafts are positioned offset from the axis of rotation R1 of the rotatable conveyor 222. The rotatable conveyor 222 and / or the winding devices are configured to wind the elongated formulation 212 at the mounting position 243.3, particularly if the rotatable shaft 223.1 is positioned in front of and within the opening 16, such that the formation of a compressed state of the formulation 2 occurs at the compressed position shown in Figures 9a and 9b, which is located in front of and even within the opening 16—and therefore at least partially directly within the hollow space 14 of the first semi-capsule shell 11; 11'—when the first semi-capsule shell is in the mounting position at 243.3. This method significantly facilitates the transfer of formulations to capsules.

[0206] Figure 9b exemplarily shows the mounting device 201 of Figure 9a. In the second step, the elongated formulation 212 is easily rolled up and immediately cut by the cutting device 230.

[0207] The production machine includes a cutting device 230 for cutting the formulation to form a preparation, which will be inserted into the hollow space of a first semi-capsule shell. The cutting device includes a first component 231 having a first cutting edge and a second component 232 having a second cutting edge.

[0208] Figure 9c exemplarily shows the installation device 201 of Figure 9b, in which, in the third step, the elongated formulation 2 is easily rolled up, cut from the storage roll 212, and inserted into the hollow space 14 of the first semi-capsule shell 11 through the opening 16 by the actuation of the actuation device 233 (which is part of the second component 232). The production machine includes the actuation device 233 for moving the compressed formulation 2 from the compacting position to its end position within the hollow space 14 of the first semi-capsule shell 11.

[0209] Figure 10a shows a schematic cross-section of a drug delivery device 1000 with a drug dosage form 1002 having a formulation 1013 disposed within the bottom 1005 of a delivery device handle 1007, and the delivery device being covered by an applicator cap 1003 with a lid 1004. The bottom 1005 is indicated by dashed lines to separate the bottom from the top (i.e., the cap 1003), and these two parts together form the housing 1006 of the delivery device 1000. The dosage form 1002 is located inside the housing 1006, specifically inside the handle 1007. Thus, the dosage form 1002 is disposed vertically within the handle 1007, i.e., along an axis indicating its elongated shape. The handle 1007 includes bars 1007a. A bar extending along dosage form 1002 serves to support dosage form 1002, i.e., the capsule device stands upright inside the grip structure 1007. A retainer 1008 is wound around the bar 1007a. The dosage form 1002 also includes a settling element 1009. The bar structure of the grip 1007 allows the dosage form from 1002 to move in the vertical direction indicated by the arrow.

[0210] Figure 10b shows a schematic cross-section of the applicator as shown in Figure 10a. When the applicator 1000 is inverted or shaken, a curved holder 1010 is positioned on the spherical cap of the dosage form 1002 to prevent vertical movement of the dosage form 1002. Therefore, the holder 1010 preferably has an outer contour similar to the end cap of the dosage form 1002. Further, the holder 1010 is secured by a spring 1011, which also presses the holder 1010 against the cap of the dosage form 1002. Therefore, the dosage form 1002 cannot move vertically. In addition, the cap 1004 of the applicator 1000 includes a desiccant 1012 to prevent the dosage form 1002 from becoming unusable.

[0211] Figures 11a and 11b schematically depict views of a capsule device 13 having a first half-capsule shell 11, 11' and a second half-capsule shell, which are nested together at an engagement position to form the capsule device 13. The corresponding overlapping areas between the two half-shells 11, 11', 12, 12' are indicated by dashed lines. In Figure 11a, the first half-capsule shell 11' includes an opening 16' formed as a slit in the capsule wall. The opening 16' can be punched into the capsule half 11' using a punching tool. If an opening is formed in the capsule wall material using a punching tool, the punched-out capsule wall material can be removed from the capsule using a suction device (e.g., vacuum suction), ideally integrated into the punching tool. The second half-shell 12 slides over the first half-shell 11' to form an engagement position, where the first half-shell 12 does not overlap with the first half-shell 11' to ultimately form a small hole 15. A hollow cylindrical wall structure 17, for example, made of capsule material adapted to the external geometry of the half 11', closes the opening 16' of the half-shell 11' like a patch to form a small hole 15. In the embodiment shown in Figure 11a, the opening 16 of the first half-shell is formed as a groove, and the hollow cylindrical wall structure 17 overlaps with the first half-shell 11 and the second half-shell 12, wherein the small hole 15 is formed in the first half-shell 11. In this embodiment, both the first and second half-shells preferably include the hollow cylindrical wall structure 17. In another embodiment not shown, the hollow cylindrical wall structure 17 preferably overlaps only with the first half-shell 11, and the small hole 15 is substantially formed at the joint where the second half-shell terminates, thereby preferably only the first half-shell includes the hollow cylindrical wall structure.

[0212] Figure 11b shows a similar construction to that shown in Figure 11a, wherein the opening 16 of the first semi-capsule shell 11 is not formed as a slit, but rather as a hole 16 in the wall of the semi-capsule shell 11. The hole 16 is preferably formed as an elongated aperture 16. A hollow cylindrical wall structure 17 covers the opening 15 of the first semi-capsule shell 11 like a patch, thereby forming a small aperture 15. In the embodiment shown in Figure 11b, the hollow cylindrical wall structure 17 preferably overlaps only with the first semi-capsule shell 11, while the second semi-capsule shell 12 preferably remains non-contacting, and the small aperture 15 is substantially formed at the junction where the second semi-capsule shell terminates. In this embodiment, preferably only the first semi-capsule shell includes the hollow cylindrical wall structure 17. In an alternative embodiment not shown, the hollow cylindrical wall structure 17 overlaps with both the first and second semi-capsule shells 11 and 12, and the small aperture 15 is formed in the first semi-capsule shell 11, thereby the first and second semi-capsule shells 12 constitute a hollow cylindrical wall structure.

[0213] In the embodiments shown in Figures 11a and 11b, as an example of all embodiments, the capsule device 13 further includes an elongated strip 18 (e.g., a biodegradable adhesive strip) for mechanically connecting the two half-capsules 11, 12 at the connection point to form the capsule device 13.

[0214] 1: Drug dosage form

[0215] 2: Formulation

[0216] 2a: Formulation end

[0217] 3: Capsule device

[0218] 3a: First half-capsule shell

[0219] 3b: Second half-capsule shell

[0220] 4: Hollow space

[0221] 5: Small hole

[0222] 5a: Surface of the capsule wall

[0223] 6: The opening of the first capsule shell

[0224] 7: Formulation end portion

[0225] 8: Hollow cylindrical wall structure

[0226] 8a: Surface of a hollow cylindrical wall structure

[0227] 10: Drug dosage form

[0228] 11: First half capsule shell

[0229] 11a: Spherical cap

[0230] 11b: Hollow cylindrical wall

[0231] 11c: Capsule wall

[0232] 11d: Capsule wall region

[0233] 12: Second half capsule shell

[0234] 12a: Spherical Cap

[0235] 12b: Hollow cylindrical wall

[0236] 12c: Capsule wall region

[0237] 13: Capsule device

[0238] 14: Hollow Space

[0239] 15: Small hole

[0240] 16: Opening

[0241] 17: Hollow cylindrical wall section

[0242] 18: Long strip of cloth

[0243] 60: Settling element

[0244] 901: Drinking Cup

[0245] 902: Drug Delivery Device

[0246] 903: Capsule Device

[0247] 904: Retainer

[0248] 905: Formulation

[0249] 100: Machine

[0250] 101: Holder

[0251] 101a: Retainer end

[0252] 102: Drug delivery device handle

[0253] 105a: First half-capsule shell

[0254] 105b: Second half-capsule shell

[0255] 106: Gripper

[0256] 107: Guiding device

[0257] 108: Cutter

[0258] 109: Support Clutch

[0259] 110: Cutting Unit

[0260] 111: Drug delivery device casing

[0261] 112: Axis

[0262] 113: Combined with the region

[0263] 114: Support component

[0264] 115: Settling element

[0265] 116: Clamping element

[0266] 117: End Cap

[0267] 701: Formulation

[0268] 702: Retainer

[0269] 200: Production machinery

[0270] 201: Installation device

[0271] 210: Storage device

[0272] 211: Axis

[0273] 212: Formulation Storage Volume

[0274] 212a: Formulation end

[0275] 213: Guiding Unit

[0276] 214: Roll

[0277] 220: Transport equipment

[0278] 222: Rotating disc

[0279] 223.1: Clamping device

[0280] 223.2: Clamping device

[0281] 230: Cutting device

[0282] 231: First component of the cutting device

[0283] 232: The second component of a cutting device with a cutting blade

[0284] 233: Actuation device

[0285] 240: Positioning device

[0286] 241: Rotatable platform

[0287] 242: Axis

[0288] 243.1: Clamping Components

[0289] 243.2: Clamping Components

[0290] 243.3: Clamping Components

[0291] 243.4: Clamping Components

[0292] 251:Feeding device

[0293] 252: Apparatus

[0294] 260: Connecting device

[0295] 261: Moving elements

[0296] 270: Receiving Station

[0297] 280: Control device

[0298] 1000: Drug delivery device

[0299] 1002: Drug dosage form

[0300] 1003: Drug delivery device cover

[0301] 1004: Lid

[0302] 1005: Bottom of the drug delivery device

[0303] 1006: Outer shell

[0304] 1007: Grip

[0305] 1008: Holder

[0306] 1009: Settlement element

[0307] 1010: Bending and fixing mold

[0308] 1011: Spring

[0309] 1012: Desiccant

[0310] 1013: Formulation

[0311] A: Capsule long axis

[0312] B: The junction between the two semi-capsule shells

[0313] H: Capsule height

[0314] W: Capsule width

[0315] a: Width of the small hole

Claims

1. A capsule device (13) for application to a mucosa, particularly for buccal or gastrointestinal mucosa, especially esophageal mucosa, configured to contain a pharmaceutical preparation (2) having an elongated shape and comprising an active pharmaceutical ingredient, the preparation being capable of being configured into a compressed state and an elongated state, the capsule device (13) comprising a hollow space (14) for containing the compressed preparation (2), the capsule device (13) having an aperture (15) configured to allow a first end (2a) of the compressed preparation to extend through the aperture (15), such that the preparation can be transferred from a compressed state in the hollow space (14) to an elongated state in the region surrounding the capsule device (13), the capsule device (13) comprising a first half-capsule shell (11; 11') and a second half-capsule shell (12) engaged by overlapping the first half-capsule shell (11; 11') and the second half-capsule shell (12) to an engagement position, wherein, The capsule device (13) further includes a hollow cylindrical wall structure (17; 17'), wherein the first semi-capsule shell (11; 11') has a hollow cylindrical wall (11c; 11c') including an opening (16; 16'), and the cross-section of the hollow cylindrical wall structure (17; 17') overlaps with that of the opening (16; 16'), thereby forming the small hole (15) of the capsule device (13) at the engagement position.

2. The capsule device as claimed in claim 1, wherein a first end (11a) of the hollow cylindrical wall (11c) of the first semi-capsule shell (11) is closed and a second end (11b) is open, and wherein the opening (16) is completely surrounded by the material of the hollow cylindrical wall (11c).

3. The capsule device as claimed in claim 1, wherein the first end (11a) of the hollow cylindrical wall (11c') of the first semi-capsule shell (11) is closed and the second end (11b) is open, wherein the opening (16') is formed as a groove starting from the second end (11b) and extending toward the first end (11a).

4. The capsule device as claimed in any of the preceding claims, wherein the cross-sectional dimensions of the opening (16; 16') are configured to receive the compressed formulation (2) before the first half-capsule shell (11; 11') and the second half-capsule shell (12; 12') are joined, wherein preferably at the joined position, the cross-sectional dimensions of the orifice (15) defined by the opening (16) and the hollow cylindrical wall structure (17; 17') are designed to prevent the compressed formulation (2) from passing through the orifice (15).

5. The capsule device as claimed in any one of claims 1 to 3, wherein the dimension A_o of the cross-section of the aperture (15) is a fraction f of the dimension A_a of the cross-section of the opening (16; 16'), wherein A_o = f * A_a, preferably 0.0010. <f<0.7500。 6. The capsule device as claimed in any one of claims 1 to 3, wherein in the engaged position, the first half-capsule shell (11; 11') is inserted into the second half-capsule shell (12; 12').

7. The capsule device of any one of claims 1 to 3, wherein the orifice (15) is a slit-like opening configured to allow the formulation (2) to pass through the orifice (15), wherein the cross-section (CS) of the orifice (15) is larger than the cross-section of the formulation (2) when the strip-shaped formulation (2) extends through the orifice (15).

8. The capsule device as claimed in any one of claims 1 to 3, wherein the capsule device (13) is configured to be swallowed by a patient.

9. The capsule device as claimed in any one of claims 1 to 3, comprising a settling plate device (60) that occupies a portion of the hollow space and provides additional weight to the capsule device.

10. A method (100) for producing a capsule device (1; 10; 51) capable of containing a pharmaceutical preparation as defined in any one of claims 1 to 9, comprising the steps of: a) providing a first half-capsule shell (11; 11') and a second half-capsule shell (12; 12') having a hollow cylindrical wall (11c; 11c') including an opening (16; 16'); b) sliding the second half-capsule shell (12; 12') and the first half-capsule shell (11; 11') to an engagement position, and providing a hollow cylindrical wall structure that overlaps the cross-section of the opening (16; 16') thereby forming the aperture (15) of the capsule device (13) at the engagement position.

11. The method of claim 10, wherein step a) comprises the further steps of: a) providing a material to form the capsule device (13), in particular the first and second half-capsule shells; b) creating openings (16; 16') in the material of the first and / or second half-capsule shells, in particular rectangular openings (16; 16').

12. The method of claim 11, wherein the opening (16; 16') is formed in the hollow cylindrical wall material formed by the first and / or the second semi-capsule shell.

13. A pharmaceutical dosage form comprising a capsule device (13) according to any one of claims 1 to 9 and a pharmaceutical preparation (2), wherein the pharmaceutical preparation (2) has an elongated shape and contains an active pharmaceutical ingredient, and is capable of being configured in a compressed state and an elongated state.

14. A method of producing a pharmaceutical dosage form as claimed in claim 13, comprising a method of producing a capsule device (13) according to claims 10 to 12, the method comprising the steps of: a) providing the formulation having an elongated shape and containing an active pharmaceutical ingredient; b) providing a first half-capsule shell and a second half-capsule shell having a hollow cylindrical wall including an opening (16; 16'); c) receiving the formulation, particularly a compressed formulation, through the opening (16; 16') into the first half-capsule shell such that a portion or end of the formulation extends through the opening (16; 16'); d) sliding the second half-capsule shell (12; 12') and the first half-capsule shell (11; 11') to the engagement position, and providing a hollow cylindrical wall structure (17; 17') overlapping the cross-section of the opening (16; 16') thereby forming the aperture (15) of the capsule device (13) at the engagement position.

15. The method of claim 14, comprising the steps of: providing a rotating shaft (X) after step a) or b), preferably located in front of or within the cross-section of the opening (16; 16'), and winding the elongated formulation by rotating the rotating shaft, thereby preferably using the opening (16; 16') to guide and / or align the formulation until the formulation reaches a compressed state.

16. The method of any one of claims 14 to 15, comprising the step of: after step b) or c), placing a settling tablet device within at least a portion of the hollow space of the first and / or second semi-capsule shell.

17. A kit comprising a drug dosage form as claimed in claim 13, a drinking cup, and a delivery device for administering the drug dosage form to a patient, wherein the delivery device is fluidly connected to the drinking cup and contains the drug dosage form, wherein the formulation of the drug dosage form is connected to the delivery device via a retainer such that, after administration to a patient, the formulation can be pulled out from the capsule device.

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