Capsule device having a gap formed by one wall part of two half capsule shells

Abstract

The present invention relates to a capsule device and a pharmaceutical dosage form using the capsule device, which comprises at least one string- or strip-shaped preparation containing an active pharmaceutical ingredient, to be applied to a mucous membrane, in particular the buccal, intestinal, rectal or vaginal mucous membrane, the dosage form consisting of a first and a second half capsule shell and a hollow cylindrical wall part which together define the size of the gap through which the preparation is released. The present invention also relates to a method for producing the pharmaceutical dosage form.

Description

[Technical Field]

[0001] The present invention relates to a capsule device and a pharmaceutical dosage form for application to a mucous membrane, particularly the buccal or gastrointestinal mucosa. The present invention also relates to a method for producing the capsule device and a pharmaceutical dosage form comprising the capsule device. [Background technology]

[0002] Such capsule devices are known from Patent Document 1 and Patent Document 2. The capsule device of Patent Document 2 is designed to include at least one sheet-shaped, specifically film-, foil-, or wafer-shaped, preparation containing an active pharmaceutical ingredient, a release mechanism, and an actuating mechanism, the actuating mechanism being adapted to trigger the release of the sheet-shaped preparation by the release mechanism at a predetermined site of action, specifically the gastrointestinal tract, the rectum, or the vagina. From the embodiments shown in Figures 8a, 8b, and 8c of Patent Document 2, a dosage form containing an active pharmaceutical ingredient and having an elongated, strip-shaped preparation is known, the preparation being capable of being arranged in a compressed state and an expanded state, the dosage form having a capsule with a hollow space containing the compressed preparation, the capsule device having an opening and a first end of the preparation extending through the opening in the compressed state, which allows the preparation to be pulled from the hollow space to the surrounding area of ​​the capsule, thereby transitioning the preparation from the compressed state to the expanded state.

[0003] Furthermore, it is known in the art to use catheter or stent-like devices for the local application of active ingredients, with particular reference to the treatment of gastrointestinal mucosa, particularly the esophageal mucosa. Another approach uses a liquid or gel-like vehicle having a relatively high viscosity. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2020 / 183005A1 [Patent Document 2] International Publication No. 2016 / 102067A1 Summary of the Invention [Problem to be solved by the invention]

[0005] The underlying object of the present invention is to provide a capsule device that can be efficiently produced, and to provide a method for efficiently manufacturing capsule devices and pharmaceutical dosage forms, as well as a method for manufacturing pharmaceutical dosage forms, including a method for manufacturing a capsule device. [Means for solving the problem]

[0006] The problem is solved by a capsule device according to claim 1 and a method for manufacturing a capsule device of a pharmaceutical dosage form according to claim 10. Preferred embodiments of the invention are the subject of the dependent claims.

[0007] According to the present invention, a capsule device includes a first half capsule shell and a second half capsule shell, and the first half capsule shell and the second half capsule shell are joined by overlapping the first half capsule shell and the second half capsule shell at a joining position, the first half capsule shell has a hollow cylindrical wall including an opening, and a further hollow cylindrical wall part is provided that overlaps with the cross section of the opening, thereby forming a gap in the capsule device at the joining position.

[0008] Thus, the joining position refers to the position where the first and second capsule half shells fit or slide against each other, thereby forming the capsule device. Partially forcing the first and second capsule half shells against each other mechanically connects the two halves and effectively stabilizes them. The joining position is defined when the two halves are pressed against each other to such an extent that the compressed, i.e., rolled, preparation can be easily inserted into the opening of the first capsule half shell. If necessary, the joining position can also be defined by slightly further pressing the two halves together after the compressed preparation is inserted, so that the compressed preparation can no longer be removed from the opening. If necessary, the joining position can also be defined by the two halves being pressed against each other, so as to facilitate rolling the preparation within the hollow of the capsule device. The joining position can also be understood as a loose adjoining of the first and second capsule half shells. In this case, the two capsule half shells are held together by a connecting mechanism. This can be implemented in the form of a band, for example an adhesive tape, a mechanical fastening by means of grooves in both capsule halves, or a partly hollow cylindrical wall part.

[0009] The hollow cylindrical wall part can be provided in the form of a film or sheet that can be made of the same material as one of the half capsule shells. For example, the hollow cylindrical wall part can be stamped from the outer surface of the cylinder, but the curvature of the hollow cylindrical wall part can match the curvature of the capsule device in the area of ​​the opening, and thus be configured to partially cover the opening like a patch. Alternatively, a tape can be used as a hollow cylindrical wall part suitable for use in, for example, a pharmaceutical dosage form, and the tape can be degraded within the patient's body.

[0010] The first half capsule shell having an opening functions as a container that can be easily filled with a pharmaceutical preparation through the opening, or alternatively, the open end of the first half capsule shell. The second half capsule shell functions as an additional container that also helps to mechanically stabilize the capsule device. Therefore, the pharmaceutical dosage form according to the present invention has excellent mechanical stability, which is advantageous for patients when swallowing the capsule. Furthermore, the pharmaceutical dosage form can be efficiently produced by the method according to the present invention.

[0011] The term "half capsule shell" refers to the fact that the capsule device is preferably composed of two parts called "halves." The dimensions, e.g., size, of the two halves may differ from each other, but in a preferred embodiment, the two halves are dimensioned to have substantially the same dimensions, i.e., the same size. Each of the first and second half capsule shells has a hollow cylindrical wall. The hollow cylindrical wall preferably has a round shape, and is preferably capped by a cap part having a hollow hemispherical shape. In addition to the first and / or second half capsule shells, there may be at least one third part used to form the capsule device. The third part may be, for example, a cylindrical or annular element. The first and / or second half capsule shells may be connected to each other at the joining location by a press-fit connection, a form-fit connection, and / or an adhesive or welding.

[0012] The first half capsule shell preferably has a hollow cylindrical wall that is closed at a first end and open at a second end, and the opening is preferably completely surrounded by the material of the hollow cylindrical wall. In this way, the first half capsule shell, particularly the wall around the opening, remains mechanically stable and provides strength to the capsule device.

[0013] Alternatively, the hollow cylindrical wall of the first half capsule shell is preferably closed at the first end and open at the second end, with the opening formed as a recess beginning at the second end and extending toward the first end, thereby maximizing the size of the opening and allowing for easier assembly of the pharmaceutical dosage form.

[0014] Preferably, at the joining position, the first half capsule shell is inserted into the second half capsule shell. Preferably, at the joining position, the second half capsule shell is inserted into the first half capsule shell.

[0015] Preferably, the cross-section of the opening is dimensioned to accommodate a preparation in a compressed state before joining the first and second half capsule shells. Preferably, at the joining position, the gap defined by the opening and the hollow cylindrical wall part has a cross-section dimensioned to prevent the preparation in the compressed state from passing through the gap. The term "cross-section of the opening" refers to the area occupied by the opening in the wall of the first half capsule shell. The term "cross-section of the gap" refers to the area occupied by the gap when the hollow cylindrical wall parts intersect or overlap.

[0016] Specifically, the second half capsule shell may include a second opening or a second indentation that overlaps with the opening or indentation of the first half capsule shell at the joining position. In this way, higher flexibility is obtained to position the hollow cylindrical wall part and obtain a gap along the length of the capsule device (the length is measured along the axis A passing through the capsule device, specifically the cylindrical axis A).

[0017] Preferably, the size A_o of the cross-section of the gap is a fraction f of the size A_a of the cross-section of the opening, A_o = f * A_a, 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 adapted to allow a strip-shaped preparation to be pulled out of the gap.

[0018] Preferably, the gap is a slit-shaped gap configured to allow a strip-shaped preparation to pass through the gap, and the cross-section (CS) of the gap is larger than the cross-section of the strip-shaped preparation when the strip-shaped preparation extends through the corner.

[0019] Preferably, the capsule device is adapted to be swallowed by a patient.

[0020] Preferably, the capsule device includes a weight device that occupies a portion of the hollow space and provides additional weight to the pharmaceutical dosage form. In one embodiment, the weight is located in one of the half capsule shells. Preferably, the weight is located in the second half capsule. Thus, the second half capsule includes a retaining means, such as a notch, for roughly positioning the weight within the hollow space of the second half capsule, so that when the capsule is turned upside down, the weight remains within the hollow space of the second half capsule and does not slide into the first half capsule, for example, due to gravity, preventing the weight from sliding into the preparation. The notch can be created by pinching the exterior of the capsule and curving it inward.

[0021] The shape of the gap preferably corresponds to the outer contour of the elongate preparation in a plane perpendicular to the long axis of the elongate preparation. For example, in the case of a strip-shaped preparation, a slit-shaped gap is preferred, and in the case of a string-shaped preparation, a circular gap may be provided. Here, the gap provides an essentially rectangular passage cross-section, and the cross-section of the strip-shaped preparation is also essentially rectangular. In the case of a string-shaped preparation, the gap may provide a circular passage cross-section, and the cross-section of the strip-shaped preparation may also be essentially circular. In this way, the movement of the elongate preparation relative to the capsule device is guided by the gap, and the relative positions of the preparation and the capsule device are stable during the extraction of the preparation from the capsule device.

[0022] Preferably, the gap is a slit-like gap configured to allow the strip-like preparation to pass through the gap, and preferably the cross section (CS) of the gap is larger than the cross section of the strip-like preparation when it moves through the corner. In this specification, the cross section of the gap defines a surface, and the cross section of the strip-like preparation is preferably measured within said surface, and the strip-like preparation is preferably positioned centrally within the gap.

[0023] The gap distance S of the gap cross section between the elongated preparation and the surface of the capsule device defining the gap is preferably measured when the cross section of the gap and the cross section of the elongated preparation are centered and an imaginary axis A extends longitudinally through the capsule device. The gap dimension resulting in the gap distance S is preferably calculated by a = t + 2 * S, where a is the diameter or width of the gap and t is the diameter of the string-like preparation or the thickness of the strip-like preparation. See Figure 1c. S is preferably in the range of 10 to 2000, 20 to 1500, 50 to 1000, 100 to 750, 200 to 500, or 300 to 400 micrometers (μm). S is greater than zero, preferably greater than the value t, specifically S = f * t, where f is a numerical coefficient selected from 1 to 20, preferably 2 to 15, and more preferably 3 to 12. The dimension a is preferably selected 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), respectively.

[0024] In the case of strip-shaped preparations and slit-shaped gaps, the length c of the cross section of the passage through which the strip-shaped preparation passes when pulled outward is greater than the width w of the strip of the strip-shaped preparation. The cross section of the passage is greater than the cross section of a coplanar elongated preparation.

[0025] Generally, a capsule device is a container configured for buccal or gastrointestinal administration, respectively. Specifically, a capsule device is a swallowable object. This specifically means that the dimensions and external shape of the capsule device are suitable for swallowing the capsule device. Specifically, the dimensions relate to the geometric size of the capsule.

[0026] The first half capsule shell may further comprise a sliding surface configured to guide the second half shell when the first half shell and the second half shell are fitted together to form the capsule device, and further, the opening of the first half capsule shell may extend into the sliding surface, such that when the first half shell and the second half shell are fitted together, the opening is partially covered by the second half shell.

[0027] The capsule device may have an elongated shape, meaning that the length measured along an imaginary central axis A of the capsule device is greater than its lateral outer dimensions. Without considering clearances, the capsule device may be rotationally symmetric about the central axis A.

[0028] The capsule device may have two or more gaps, specifically two gaps or three or more gaps.

[0029] The present invention relates to a method for manufacturing a capsule device as defined in any of the preceding claims, comprising at least 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') into a joining position to provide a hollow cylindrical wall part that overlaps the cross section of the opening, thereby forming a gap (15) in the capsule device at the joining position.

[0030] The term "sliding" refers to joining or fitting a first capsule half shell to a second capsule half shell, or vice versa, so that both halves reach an overlapping position. This may include a locking mechanism, e.g., mechanical friction of the sliding surfaces formed by one or both of the two halves. This secures both halves together, thereby eliminating the need for any additional manufacturing steps to join the two halves together in a manner suitable for application in the dosage form. However, process steps, preferably performed by machine, may also be required to join the halves in a manner suitable for application, e.g., by heating or welding, especially by bonding materials.

[0031] Preferably, the method of manufacturing a capsule device comprises: a) providing materials for forming a capsule device, specifically a first half capsule shell and a second half capsule shell; b) creating an opening, particularly a rectangular opening, in the material of the first and / or second half capsule shells.

[0032] For example, in the case of a circular opening, the first and second capsule halves may each have an arc-shaped opening, so that the halves that slide together into a mating position form a circle or an oval, which is advantageous when a preparation having a circular cross-section is used.

[0033] The step of forming the capsule device using the material for forming the capsule device may be applied after the step of creating an opening in the material of the first half capsule shell, or the step of forming the capsule device using the material for forming the capsule device may be applied before the step of creating an opening in the material of the first half capsule device.

[0034] The opening or recess may be created using a workpiece having a suitable shape, for example by a punching tool. The workpiece may be a material from which the capsule device is formed. In each preferred embodiment, the workpiece may have the shape of a cube, a foil, a hollow cylinder, a capsule, or half a capsule.

[0035] Preferably, the method includes the step of creating an opening in the material of the hollow cylindrical wall of the first half capsule shell and / or the second half capsule shell.

[0036] That is, the openings can be created in the wall material of the first and / or second half capsule shells before the actual shell shape is formed, i.e., the openings are created in a two-dimensional material shape, and then the shell shape is formed in a further step. Alternatively, the openings are created in the half capsule shells, i.e., the openings are created in the wall material of the first and / or second half capsule shells after the actual shell shape is formed, i.e., the openings are created in the three-dimensional material shape that forms the shell in a shape-making step.

[0037] The opening may be created using a laser to cut or peel the material from the capsule material. Furthermore, a punch may be used to create the opening through the capsule material and create a rectangular hole by shearing. However, it may be preferable for the opening to be created by injection molding a material suitable for forming the capsule device, such as plastic. The gap preferably has the shape of a planar curved slit. The planar nature of the curved slit provides the advantage of facilitating the passage of the strip-shaped preparation through the slit in the pulling direction P, thereby further improving the reliability of the mechanical process of expanding the preparation from a compressed state to an expanded state. When the opening in the capsule wall material is created by a punch tool, the punched material of the capsule wall can be transported from the capsule by a suction device, ideally integrated into the punch tool, for example, by negative pressure suction.

[0038] The capsule device preferably has an elongated shape and is formed such that when a preparation containing an active pharmaceutical ingredient is inserted into the hollow space of the capsule device in a compressed state of the preparation, an end portion of the preparation extends through the gap and the preparation can be pulled out of the gap, a gap cross section (CS) of the gap between the preparation and a surface of the hollow cylindrical wall part defining the gap is spaced. The capsule device is preferably formed so as to be swallowable by a patient.

[0039] The step of forming the opening may include at least one of the following features. Use of a plane milling tool, such as a plane saw blade, or another tool that results in a plate-shaped cutout, such as a cylindrical milling head that performs a transverse movement Use of a horizontally moving water jet in abrasive water jet cutting processes Use of a laser to cut or ablate material from the encapsulant Punching of half capsule shell material to create holes by shearing Injection molding of suitable materials, e.g. plastics, to form the semi-capsule shells

[0040] Forming the capsule device may include applying a dip-molding process to manufacture two half capsule shells of the capsule device that are joined to form a capsule, for example essentially as described in EP 0 102 832. Forming the capsule device may include applying an additive manufacturing process to form the capsule from a suitable material, in particular a three-dimensional printing process to form the capsule from a suitable material. Forming the capsule device may include injection molding the capsule from a suitable material.

[0041] The capsule device may be a capsule including a hollow cylinder capped on both sides by curved cap members. The cap members may have an essentially hemispherical shape. A cap member having a cylindrical portion as one piece may be manufactured. Two parts of the capsule device may be joined to form the capsule device. This facilitates assembling the dosage form by first placing the preparation inside one of the two parts and then joining the two parts of the capsule device to fix the preparation. The capsule may also be shaped with an oval or elliptical cross section, such that the capsule has an olive shape, for example.

[0042] In a preferred embodiment, the capsule device is configured such that the gap is offset from the central axis A. This means that the central axis A does not intersect the cross-section of the gap, or that the central axis A does not intersect the center point of the cross-section of the gap. An advantage of such an embodiment is that when the preparation is pulled out of the capsule device and the capsule device is administered to a patient, the force acting on the wall of the capsule device is reduced, thereby reducing the risk of damaging the capsule device. Experiments by the inventors have shown that, particularly for strip-shaped preparations, it is easier to unwind a wound preparation from a gap that is positioned offset from the central axis A than from a central position of the gap (where the central axis A of the capsule device extends through the center of the gap).

[0043] In the case of a slit-shaped gap, the gap is preferably positioned offset from the central axis A of the capsule device. The slit is preferably formed by opposing surfaces of the walls forming the capsule device and the hollow cylindrical wall part.

[0044] For example, if the first half capsule shell and cut mass are considered as three-dimensional mathematical objects, the preferred shape of the slit is achieved by first preparing the opening by milling the cylindrical wall and / or hollow cylindrical wall component forming the first half capsule shell, thereby removing a plate-shaped mass from the wall. The orientation of the plate-shaped mass removed from the capsule material is specifically characterized by the orientation of the major plane of the plate-shaped mass relative to the direction of the imaginary central axis A of the capsule device.

[0045] The hollow space within the capsule device is defined by at least one interior wall of the capsule device, specifically the first and second half capsule shells.

[0046] 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 hollow space. Preferably, the inner side (inner surface) and the outer side (outer surface) extend parallel to each other. This means 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. Such a configuration makes it possible to define auxiliary structures within the capsule device, which can serve to guide the movement of the preparation within the capsule device or other functions.

[0047] Preferably, the accessory structure is an inner guide wall of the capsule device arranged to guide the unwinding and / or unwinding of the preparation within the capsule device. The guide wall is arranged to guide the positioning of the preparation during unwinding and / or unwinding. The guide wall may be arranged parallel to the movement direction P in which the preparation moves within the capsule device towards the gap. Preferably, the guide wall is arranged to be aligned with the gap. For example, the guide wall is preferably parallel to the longitudinal direction of the gap, i.e., parallel to the Y direction as defined in FIG. 1a. The guide wall may also be realized by a protrusion in the region of the inner wall of the capsule device. In this case, the preparation is arranged to unwind through the gap. Such a protrusion in the wall of the capsule device, or a notch seen from the outside of the capsule device, can serve to guide the preparation during unwinding, for example, by mechanically supporting the inner part of the wound preparation, i.e., the core, by allowing it to rotate, in particular during the unwinding operation of the preparation.

[0048] Preferably, one or more inner walls of the capsule device are arranged to form a guide compartment within the capsule device, the guide compartment being arranged to support the compressed preparation and aid in unwinding the preparation. Preferably, one or more inner walls of the capsule device are arranged to form side walls of a cubic hollow space that contains the compressed preparation.

[0049] Preferably, the capsule device includes a guide member. The guide member is disposed within the inner space of the capsule device and guides the movement of the string-like or sheet-like preparation toward the gap of the capsule device. The guide member may be a part of the inner wall of the capsule device, or a part supported by or connected to the inner wall of the capsule device, specifically a wall member. For example, the guide member may be a guide lip or a guide spout disposed on one side of the edge of the gap, or may be attached around the entire periphery of the gap or opening.

[0050] Preferably, the capsule device may include an attachment structure configured to guide the rolling and / or unrolling of a string of preparation or the rolling and / or unrolling of a strip of preparation, particularly by rolling or winding the preparation around one or more rods or cylinders of the attachment structure. The rods or cylinders may be rotatably disposed within the capsule device to facilitate rolling or unwinding.

[0051] In another preferred embodiment, the capsule device and the pharmaceutical dosage form each include a weight device. The weight device is configured to provide negative buoyancy to the capsule device. The inventors' experiments, which form the basis of the findings of this preferred embodiment, have shown that reducing the buoyancy, for example by increasing the mass of the capsule device, improves the swallowability of the capsule device, i.e., improves the reliability of the mechanical process of unfolding the preparation from a compressed state to an unfolded state. In the case of a strip-shaped preparation, unwinding the preparation from a compressed state to an unfolded state, in which the strip-shaped preparation is wound around a winding axis, becomes significantly easier and more efficient. For example, such weights are described in WO 2020 / 183005.

[0052] In another preferred embodiment of the capsule device, the hollow cylindrical wall part completely overlaps the cross section of the opening of the first half capsule shell when the first and second half capsule shells are joined in the joining position, in which case the hollow cylindrical wall part includes a gap through which the preparation extends partially.

[0053] In another preferred embodiment of the capsule device, the hollow cylindrical wall part completely overlaps the cross section of the opening of the first half capsule shell and the further opening of the second half capsule shell when the first and second half capsule shells are joined in the joining position, in which case the hollow cylindrical wall part includes a gap through which the preparation extends partially.

[0054] In another preferred embodiment of the capsule device, the hollow cylindrical wall part completely overlaps the cross section of the opening of the first half capsule shell and optionally the further opening of the second half capsule shell when the first and second half capsule shells are joined at the joining position, and the hollow cylindrical wall part further secures the two halves to each other to form the capsule device. For example, the hollow cylindrical wall part is also glued to the first half capsule shell and optionally the second half capsule shell, thereby mechanically securing both halves together.

[0055] In another preferred embodiment of the capsule device, the hollow cylindrical wall part is made of a flexible and / or elastic material and includes an opening. In this case, the material properties of the hollow cylindrical wall part are selected so that the preparation is not obstructed by the edges of the capsule device wall during unwinding from the capsule device. Optionally, the material properties of the hollow cylindrical wall part are selected to assist in sealing the capsule internally, for example, against humidity. Further optionally, the opening in the hollow cylindrical wall part is dimensioned such that the elastic material properties of the hollow cylindrical wall part allow the opening to conform to the contours of the preparation, thereby further assisting in sealing the capsule device. Pressure applied to the opening as the preparation is pulled out expands or widens the opening, thereby allowing the preparation to leave the capsule device through the opening while the patient swallows the capsule device.

[0056] 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 placed in a compressed and expanded state.

[0057] The present invention also relates to a method of manufacturing a pharmaceutical dosage form, the method comprising the steps of a method of manufacturing a capsule device according to the invention, further comprising: a) providing a preparation having an elongated shape and comprising one or more active pharmaceutical ingredients; b) providing a first half capsule shell and a second half capsule shell having a hollow cylindrical wall including an opening; c) placing the preparation, preferably in a compressed state, into the first half capsule shell through the opening so that a portion or end of the preparation extends through the opening; d) sliding the second half capsule shell (12, 12') and the first half capsule shell (11, 11') into the joining position to provide a hollow cylindrical wall part that overlaps the cross section of the opening, thereby forming a gap (15) of the capsule device at the joining position.

[0058] Preferably, the method comprises: After step a) or step b) of the method for producing a pharmaceutical dosage form, the method further comprises the steps of providing a rotation axis (X), preferably positioning the rotation axis (X) in front of the opening or within the cross section of the opening, and rotating the rotation axis until the preparation reaches a rolled and compressed state, thereby preferably rolling the elongated preparation using the opening to guide and / or align the preparation. In this way, any problems with unrolling the preparation before it reaches the interior of the capsule can be reduced or eliminated, since the compressed form of the preparation is formed within the opening and inside the first half capsule device.

[0059] Preferably, the method for producing a pharmaceutical dosage form comprises: After step b) or c) of the method of producing the pharmaceutical dosage form, the method may include the step of disposing a weight device in at least a portion of the hollow space of the first and / or second half capsule shell, the weight device providing additional weight to the pharmaceutical dosage form, which may, in particular, facilitate swallowing of the pharmaceutical dosage form.

[0060] Preferably, any of the steps of the method, particularly the loading of the compressed form preparation into the first half capsule shells, is preferably performed automatically by machine for producing multiple pharmaceutical dosage forms in parallel, thereby increasing the throughput of producing a large number of pharmaceutical dosage forms per hour.

[0061] The step of placing or storing a preparation having an elongated shape and containing an active pharmaceutical ingredient in a compressed state of the preparation in a hollow space of the capsule device and extending an end portion of the preparation through the gap includes the gap and the preparation configured such that when the preparation is pulled out of the gap, a gap cross section (CS) of the gap between the preparation and the surface of the capsule device that defines the gap is spaced.

[0062] The step of placing the preparation is preferably carried out by placing the preparation in the first part or first half capsule shell, and then preferably extending an end portion of the preparation through the gap and connecting the second part or second half capsule shell to the first part or first half capsule shell. The first part or first half capsule shell and the second part or second half capsule shell may be a pipe element or a capped pipe element, respectively, or a cylindrical section, in particular a semi-cylindrical element.

[0063] The present invention also relates to a kit comprising a pharmaceutical dosage form as defined in claim 13, a drinking cup and an applicator for administering the pharmaceutical dosage form to a patient, wherein the applicator is in fluid connection with the drinking cup and contains the pharmaceutical dosage form, and wherein the pharmaceutical dosage form preparation is connected to said applicator by a retainer for withdrawing the preparation from the capsule device after administration to the patient.

[0064] The capsule device and pharmaceutical dosage form comprising the pharmaceutical preparation according to the present invention are particularly suitable for application to mucous membranes, particularly buccal or gastrointestinal mucous membranes, especially mucous membranes in the upper gastrointestinal tract, such as the throat, esophagus, cardia, and / or stomach. Pharmaceutical dosage forms comprising the pharmaceutical preparation and their applications are described in WO 2016 / 102067, which is incorporated herein by reference in its entirety, particularly in relation to the shape, size, and (chemical) composition of the capsule device and pharmaceutical preparation, the active pharmaceutical ingredients, and the treatment and prevention of specific conditions and diseases already disclosed therein. Thus, in other words, the chemical components of the capsule device and pharmaceutical preparation are described, at least to a considerable extent, in the above-mentioned references. This also applies to capsules.

[0065] Advantageously, the pharmaceutical dosage form of the present invention allows for increased bioavailability of the active pharmaceutical ingredient at the desired site of action.

[0066] The pharmaceutical dosage form of the present invention is capable of and adapted to rapidly release a pharmaceutical preparation in the form of a string or strip, in particular in the form of a sheet, film, foil, or wafer, containing an active pharmaceutical ingredient having a systemic effect at a predetermined site of action. Furthermore, the pharmaceutical dosage form according to the present invention makes it possible to apply to a predetermined site of action active pharmaceutical ingredients that cannot be administered orally due to low bioavailability.

[0067] The preparations in the form of strings or strips, in particular films, foils or wafers, containing an active pharmaceutical ingredient may comprise a single layer or a multi-layer structure, in which a first layer may contain a first active pharmaceutical ingredient and a second / further layer may contain at least a further active pharmaceutical ingredient, thereby enabling the application of, for example, two pharmaceutical ingredients that are not compatible with each other.

[0068] Preferably, the preparation is made mucoadhesive to allow targeted release of the active ingredient. This can be achieved by providing a single layer that not only contains the active pharmaceutical ingredient but is also mucoadhesive, or by providing the preparation in multi-layer form, at least one, preferably the outermost layer, being mucoadhesive.

[0069] In a preferred embodiment, the pharmaceutical dosage form according to the invention is adapted to be administered orally.

[0070] The capsule device is made of, or primarily made of, a material that is essentially insoluble in the fluids present in the pathway that carries the capsule device to the site of administration, specifically the gastrointestinal tract. Such materials are known in the art and are described in WO 2016 / 102067. Specific examples include known gastric juice-resistant polymers, such as polymethacrylic acid (Eudragit), HPMCAS, shellac, gelatin, and the like. These may be formulated with known additives that improve processability, such as plasticizers, flavors, and flavoring agents.

[0071] The preparation is diagnostic substances, such as dyes or stains, analgesics, preferably NSAIDs, such as ibuprofen or flurbiprofen; local anesthetics, such as benzocaine, butamben, dibucaine, lidocaine, oxybuprocaine, or novocaine; antibiotics, such as penicillin, amoxicillin or vancomycin; disinfectants, such as 2,4-dichlorobenzyl alcohol, amylmetacresol or cetylpyridinium chloride; steroids, such as corticosteroids, glucocorticoids, fluticasone, budesonide, clocortolone, perdesonide, hydrocortisone, clobetasone butyrate, flumethasone, fluprednidene, hydrocortisone aceponate, hydrocortisone buteprate, hydrocortisone-17-butyrate, triamcinolone acetonide, amcinonide, betamethasone-17,21-dipropionate, betamethasone-17-valerate, desoximetasone, diflucortolone-21-valerate, fluocinolone acetonide, fluocinonide, fluticasone-17-propionate, methylprednisolone aceponate, mometasone furoate, prednylcarbate, or clobetasol-17-propionate; Parasiticides, also called parasizides, such as mebendazole, albendazole, thiabendazole, diethylcarbamazine, diaminodiphenyl sulfone, benznidazole, ivermectin, pyrantel, praziquantel, Fungicides, such as nystatin, imidazoles, triazoles, thiazoles, clotrimazole, ketoconazole, or undecylenic acid, Hexamethylpararosaniline chloride, amphotericin B, botulinum 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 The compounds contain at least one active pharmaceutical ingredient selected from the group consisting of (the drug names also include any pharmaceutically acceptable salts thereof).

[0072] Additionally or alternatively, the preparation may contain, among others, an inflammation regulator, such as montelukast, an interleukin receptor, or an interleukin antibody. Additionally or alternatively, the sheet-shaped preparation may contain, among others, beclomethasone dipropionate, budesonide, or ciclesonide, which are particularly advantageous for treating asthma. Additionally or alternatively, the sheet-shaped preparation may contain, among others, mesalazine, sulfasalazine, or olsalazine, which are particularly advantageous for treating inflammatory bowel disease.

[0073] The active pharmaceutical ingredient contained in the sheet-like preparation of the pharmaceutical dosage form according to the present invention may be selected from the group comprising proteins and peptides, in particular insulin, buserelin, desmopressin, calcitonin, and estrogen, and biotechnologically produced drugs, such as antibodies, for example rituximab. It should be understood that proteins and peptides, in particular insulin, buserelin, desmopressin, calcitonin, and estrogen, may exhibit low bioavailability, in particular low oral bioavailability, under certain circumstances, and are therefore promising candidates for the application of the dosage form according to the present invention.

[0074] Substances from the groups of drugs acting on the skeleton 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 the sensory organs, dermatological drugs, vitamins and micronutrients, peptide drugs and proteins, analgesics, anti-infectives and parasiticides may be used as active pharmaceutical ingredients.

[0075] In one embodiment, the active ingredient is selected from corticosteroids, illustratively including budesonide, mometasone, fluticasone, and ciclesonide, and pharmaceutically acceptable salts thereof.

[0076] Exemplary conditions to be treated include conditions relating to the gastrointestinal mucosa, preferably the esophagus, such as GERD, NERD, and eosinophilic esophagitis, which are successfully treated with steroids from the above groups and the nitric oxide or nitric oxide-forming agents mentioned above.

[0077] The pharmaceutical preparations contain an amount of the active pharmaceutical ingredient known to be effective for the condition to be treated, depending on the site of administration and the active ingredient, for example, the concentration / amount of budesonide in the dosage form is significantly higher compared to mometasone-containing dosage forms.

[0078] Additionally or alternatively, in certain embodiments of the capsule device according to the invention, the string or strip preparation is preferably adapted to dissolve, e.g., biologically degrade, in a time-controlled manner, e.g., within 1 hour, or within 1-2 hours, or within 1-5 hours, or within 1-12 hours, or within 1-24 hours, thereby improving user convenience, since there is no need to remove the sheet preparation.

[0079] The method for preparing the preparation containing these active ingredients is not particularly limited and is known to those skilled in the art. Furthermore, in relation to the pharmaceutical dosage form of the present invention, reference is made to WO 2016 / 102067.

[0080] Specifically, a string- or strip-shaped preparation can be prepared by a person skilled in the art by a method basically known in the art, for example, by coating an inert support with a liquid composition containing a polymer, an active pharmaceutical ingredient, and optionally additives, and a solvent, for example, by a method involving a doctor blade, a spray processor, or an extrusion processor. The thin film layer thus obtained is dried. In a multi-layer sheet-shaped preparation, one or more coatings may be applied to an existing film layer in the same manner, or may be prepared separately and then laminated.

[0081] The shape of the gap preferably corresponds to the outer contour of the elongate preparation in a plane perpendicular to the long axis of the elongate preparation. For example, in the case of a strip-shaped preparation, a slit-shaped gap is preferred, and in the case of a string-shaped preparation, a circular gap may be provided. Here, the gap provides an essentially rectangular passage cross-section, and the cross-section of the strip-shaped preparation is also essentially rectangular. In the case of a string-shaped preparation, the gap may provide a circular passage cross-section, and the cross-section of the strip-shaped preparation may also be essentially circular. In this way, the movement of the elongate preparation relative to the capsule device is guided by the gap, and the relative positions of the preparation and the capsule device are stable during the extraction of the preparation from the capsule device.

[0082] Preferably, the string- or strip-like preparation is bendable, in particular so that it can be transformed from a compressed form to an unfolded form by a folded, unfolded, rolled, rolled or coiled sheet-like preparation, which may preferably have a string-, cord-, strip- or tubular shape, for example, as exemplarily described in WO 2020 / 183005.

[0083] In a preferred embodiment of the capsule device, the preparation stored in the capsule can be expanded from a compressed form to an expanded form in order to extract the preparation from the hollow space of the capsule to the surrounding area of ​​the capsule device. Therefore, the preparation preferably includes a retaining device. When the retaining device is secured, the preparation can be extracted from the capsule device by a pulling action and / or a pulling force. The securing of the retaining device is preferably achieved by connecting the retaining device to a fastening device. Such a fastening device may be a string member, such as a cord, a string, or a rope. In this case, the fastening device prevents the retaining device from moving together with the capsule device, thereby generating a pulling force. The fastening is achieved, for example, by connecting the retaining device to one end of the cord and fastening the other end of the cord to an applicator. Therefore, when the cord of the fastening device is pulled by moving the capsule from the applicator, the retaining device establishes a pulling force, thereby extracting the preparation from the capsule device. When the retaining device is preferably part of the preparation or attached to the preparation, the retaining device may be a handle, a sling, or an adhesive tape, or may include an adhesive region. The retaining device is adapted to establish or maintain a force-transmitting connection between the retaining device and the area to which it is attached. Furthermore, this connection may be established or maintained while the dosage form and / or sheet-like preparation is in a compressed and / or expanded form. Preferably, the retaining device, and possibly further components, may be held at a defined position or area by a force fit, particularly by frictional engagement, form fit, or material engagement, particularly by mucoadhesion, preferably adhesive. For example, such a retaining device is described in WO 2016 / 102067.

[0084] The term "compressed form" as used herein preferably refers to a folded, rolled, rolled, coiled or disassembled form. Specifically, in a compressed form, a string-shaped or strip-shaped preparation has a smaller spatial extent and / or exposes a smaller amount of surface area than a non-compressed form, specifically an unfolded form. Preferably, a string-shaped or strip-shaped preparation in a compressed form is folded, disassembled, rolled, rolled, coiled, pressed, packed together or otherwise made into a smaller form. Specifically, when in a compressed form, a string-shaped or strip-shaped preparation can have a predetermined size or spatial extent.

[0085] The term "unfolded form" as used herein preferably refers to an unfolded form, an unfolded form, an unfolded form, an elongated form, an extended form, or a rectangular form. Specifically, in the unfolded form, the string-like or strip-like preparation has a larger spatial extent and / or exposes a larger amount of surface than in a non-unfolded form, specifically a compressed form. Preferably, the string-like or strip-like preparation in the unfolded form is unfolded, unfolded, unrolled, stretched, unfolded, elongated, extended, unfolded, or otherwise made into a larger form. Specifically, when in the unfolded form, the string-like or strip-like preparation can have a predetermined size or spatial extent. Alternatively, the size or spatial extent of the string-like or strip-like preparation depends on the existing conditions and the action site or application site, and therefore may not be predetermined.

[0086] In a particularly preferred embodiment, the preparation is wrapped around the outside of the capsule device. In such a case, it is intended, for example, to place the preparation in a compressed form in a first half capsule shell, and only after that, to connect the second half capsule shell to the first half capsule shell to form the capsule device. The hollow cylindrical wall part is provided to form the gap of the capsule device.

[0087] Alternatively, however, the preparation is wound inside the capsule device. When wound inside the capsule device, the preparation is advantageously provided in an unfolded state from the outside of the preparation and is fed into the capsule device during the winding, for example, through an opening and / or a gap in the capsule device. In such a case, the capsule device is preferably provided with a first half capsule shell having a hollow cylindrical wall including an opening, and the wall of the second half capsule shell optionally overlaps the cross section of the opening. After the preparation is wound inside the capsule device, a wall part used to cover the opening of the first half is provided and is arranged on the first half capsule shell and, optionally, on the second half capsule shell to form the gap in the capsule device.

[0088] Preferably, the preparation is wound mechanically, for example, by means of a winding device or winding unit. Alternatively, the preparation can be wound manually. During manual and mechanical winding of the preparation, the end section of the preparation is clamped, for example, between two holding jaws, or, if an essentially continuous preparation is used, a section of the preparation is clamped and the portion outside the clamped section is cut off, whereby the clamped section of the preparation forms the end section of the wound preparation. Further illustratively, the clamped section of the preparation is braided into the fork- or U-shaped end of a winding pin, whereby the preparation is wound around the pin end by rotating the pin. The pin around which the preparation is wound is then placed, for example, through an opening in the capsule device, and the pin is pulled out of the wound preparation. In a particularly preferred embodiment, the wound preparation is placed into the first half capsule shell through the opening.

[0089] Alternatively, the preparation is fed into the pressing chamber in an unfolded state by a conveyor, e.g., a conveyor belt. Preferably, multiple surfaces rotating in a common direction are arranged in the pressing chamber, which rotate the pulled but not yet folded preparation. Furthermore, the rotational movement of the preparation can be assisted by rollers. The principle is similar to that of a hay baler. The rotational movement of the rotating surfaces in the pressing chamber is transmitted to the preparation, which then rotates itself and thus begins to roll up. As soon as the preparation has a predetermined size and / or weight, the rotational movement stops, and the rolled preparation is extruded from the pressing chamber, for example, directly into the opening of a capsule device.

[0090] The machine that winds the preparation into a compressed form has a scale, which allows the weight to be measured during the winding process, or the weight of a section of the preparation to be wound can be measured to determine the amount of active substance contained in the preparation. Alternatively, a device can be used that measures the length, width, or thickness of the portion of the preparation to be wound, or any combination of these quantities, such as volume. In a further alternative, it is necessary to be able to determine the concentration of the active ingredient in the preparation in a compressed state.

[0091] The invention also relates to a manufacturing machine for producing pharmaceutical dosage forms according to the invention, in particular by carrying out the method of the invention, the manufacturing machine comprising a positioning device for positioning a first half capsule shell in a mounting position.

[0092] The connecting device has a movable element configured to connect the second half capsule shell and the first half capsule shell to a joining position by moving the first and second half capsule shells toward each other, whereby the wall of the second half capsule shell optionally overlaps the cross section of the opening at the joining position by an amount controlled by the movement of the movable element.

[0093] The positioning device preferably includes one or more holding members for holding one or more of the first and / or second capsule half shells in a fixed position. The holding members preferably include a fixing space shaped to fix the first and / or second capsule half shells by form-fitting. The positioning device, particularly the holding member, may be configured to hold multiple first and / or second capsule half shells in position in parallel. In this way, the throughput of the manufacturing method can be increased. A positioning device may be provided for positioning one or more of the first and / or second capsule half shells at two or more mounting positions. This allows several manufacturing steps of the pharmaceutical dosage form to be performed in parallel using multiple mounting positions, particularly work stations.

[0094] The positioning device preferably comprises a movable platform supporting one or more work stations. The work stations preferably comprise at least one or more holding members. The movable platform may be rotatably arranged on a base member rotating about an axis configured to rotate each work station to a work position of the machine. A feeder may be arranged at the first work position to supply at least one first half capsule shell to at least one mounting position provided by at least one holding member. A feeder may be arranged at the second work position to supply at least one second half capsule shell to at least one mounting position provided by at least one holding member. A loading device may be arranged at the third work position to load the first half capsule shell with the preparation, preferably in a compressed state. The loading device may optionally comprise a conveying device for transporting at least part or all of the preparation to the mounting position and / or a compressing device, particularly a winding device, for transferring the preparation from an elongated state to a compressed state, particularly a rolled or wound state. A receiving station may be arranged at the fourth work position to receive the prepared manufactured pharmaceutical dosage form and, optionally, to store or transfer the pharmaceutical dosage form to a conveyor system.

[0095] Preferably, the manufacturing machine includes a conveying device configured to convey an end of a preparation having an elongated shape and containing an active pharmaceutical ingredient from a preparation storage location to a mounting location. Here, the preparation is arranged to be inserted into the hollow space of the first half capsule shell at the mounting location, specifically through an opening. In a preferred embodiment, the conveying device has a rotatable conveying member configured to receive at least a portion of the preparation or the entire preparation at a first location, specifically from a preparation storage device, and to convey the portion of the preparation to the mounting location by rotating. The rotatable conveying member may be a rotatable rod member or a rotatable disk member. The movement or rotation of the conveying device may be controlled by an electronic control device of the manufacturing machine. The manufacturing machine and / or the rotatable conveying member may include a winding device that winds the preparation from an elongated state to a compressed state. The rotatable conveying member may include a winding device that winds the preparation from the elongated state to form a wound state. The winding device may include one, two, or more rotatable shafts configured to be electrically driven and controlled by the electronic control device of the manufacturing machine. One, two, or more rotatable shafts may be positioned offset from the rotation axis of the rotatable carrier. The rotatable carrier and / or the winding device may be configured to wind the elongated preparation in the mounting position, particularly when the rotatable shaft is positioned in front of or within the opening, so that the formation of the compressed preparation in the compressed position may occur when the first half capsule shell is in the mounting position. This is preferably positioned in front of or even within the opening, thereby immediately at least partially within the hollow space of the first half capsule shell. This significantly facilitates the transfer of the preparation into the capsule. The winding of the preparation is preferably performed using a winding pin. Therefore, the winding device preferably includes a winding pin.

[0096] Preferably, the manufacturing machine and / or the conveying device includes a compression device, in particular a winding device, for winding the preparation from an elongated state to a compressed position, or a folding device for folding the preparation from an elongated state to a compressed position, the compression preferably being carried out in the compression position of the manufacturing machine.

[0097] Preferably, the machine comprises a cutting device for cutting the preparation inserted into the hollow space of the first half capsule shell to form the preparation.

[0098] Preferably, the machine comprises an actuator for moving the compressed preparation from the compression position to a final position within the hollow space of the first half capsule shell.

[0099] Preferably, the machine further comprises a pressing device for pressing the weighting material, e.g., powder, to obtain a weighting device. Preferably, the pressing device is configured to feed the obtained weighting device to a further processing device for producing the pharmaceutical dosage form.

[0100] In one embodiment, an applicator may be used for administration that, in combination with a drinking cup, assists in swallowing the capsule device. For example, such an applicator is described in WO 2020 / 183003. This is particularly advantageous when the dosage form is to be administered regularly, in particular daily, as it allows administration of the capsule device without professional assistance.

[0101] The applicator includes a housing configured to accommodate the capsule device and a capsule holder. Preferably, the applicator further includes a spacer. In one embodiment of the applicator, the applicator is not directly attached to the opening of the drinking cup. Instead, a spacer is disposed between the drinking cup and the applicator. The spacer thereby reduces the risk of moisture from the drinking cup, for example, before residual moisture from the drinking cup seeps into the applicator, rendering the dosage form unusable prior to use. The spacer preferably has a tubular or annular shape and is preferably screwed onto the opening of the applicator and the drinking cup, respectively, after the corresponding caps have been removed. The spacer preferably has a length of 1 to 10 mm, preferably 2 to 8 mm, and most preferably 5 mm.

[0102] The present invention also relates to a retainer. The retainer is part of the applicator in that the applicator further includes a retainer. In a preferred embodiment, the retainer consists of or includes a string element. The retainer is wound around the capsule-holding device. Thus, the capsule-holding device includes a wall structure. The retainer is preferably attached to or fixed to the capsule-holding device, thereby allowing the retainer to transmit force, such as mechanical traction, to the capsule-holding device and thus the applicator. The retainer is preferably made of or includes a thread, fiber, string, or twisted yarn having a first end and a second end. The retainer is connected at its first end to one end of the preparation, e.g., the holding device of the preparation, which extends through the gap of the capsule device. The retainer is connected at its second end to the capsule-holding device of the applicator, e.g., the wall structure of the capsule-holding device. When the retainer is connected to the preparation, the retainer unwinds from the capsule-holding device when the capsule moves from the applicator and the retainer is subjected to tension. When the patient swallows the capsule, the capsule moves from the capsule-retaining device, thereby unwinding the retainer from the capsule-retaining device. As the patient swallows the capsule, the retainer will at some point completely unwind from the capsule-retaining device, increasing the tensile stress and thereby pulling the preparation from the capsule. Thus, advantageously, the retainer, e.g., the string member, allows for release of the active pharmaceutical ingredient, particularly to the mucous membranes surrounding relatively small lumens or cavities, such as the esophageal or nasal cavities.

[0103] Prior to use of the applicator, the retainer is wrapped around the wall structure of the retainer. Wrapping the retainer around the retainer prevents knots from forming in the retainer. Once the patient swallows the dosage form, the retainer is unwound from the retainer.

[0104] Winding the fastener around the structure of the holding device and / or bonding the fastener to the preparation, e.g. the string containing the preparation, or the holding device for the preparation, is preferably carried out by a machine, e.g. a winding machine and / or bonding machine, in particular in the bonding area of ​​the machine.

[0105] In the first step, the fastener is wrapped around the holding device, which is mechanically fixed to the machine and clamped, for example, by support jaws. In the second step, the fastener is tensioned. In the third step, the holding device is placed along the tensioned holding device (meaning a mechanical clutch), and the fastener is clamped in a groove in the holding device's wall structure. In the fourth step, the support jaws that clamp the fastener are opened. In the fifth step, the holding device is rotated by rotating the clutch that secures and supports the holding device, thereby wrapping the fastener around the holding device. The rotational movement of the coupling is superimposed on the vertical translational movement, thereby wrapping the fastener around the holding device in a parallel position. In the sixth step, the support jaws clamp the fastener again, and in the seventh step, one end of the fastener is cut off by a knife-like part of the machine, which then connects it to the preparation in a further step. In an eighth step, the retainer with the retainer wrapped around it is placed, particularly by a machine, over an opening in the applicator housing, preferably pushing the opening over an axis extending through the housing placed in the machine, such as an auxiliary tube, and the cut end of the retainer is placed over one end of the preparation, which is then pulled out of the capsule.

[0106] In a ninth step, the retainer is coupled to one end of the preparation at a clamp coupling region. As described, the retainer can be wound around the retainer by rotating the retainer about the winding axis, or alternatively, the retainer can be rotated around the fixed retainer to wind the retainer.

[0107] In a preferred embodiment of the applicator, the cap of the applicator, which is removed before use to cover the opening of the applicator and allow the dosage form to exit the applicator body, includes a lid and a plurality of springs configured to press the support element against the capsule, preferably against one end of the capsule placed in the holding device, which preferably faces the cap. For example, the cap is similar to a cap for an effervescent tablet.

[0108] Thus, in a preferred embodiment, the capsule is positioned vertically in the holding device and the support element is pressed towards one end of the capsule that faces the lid. The lid preferably further comprises a desiccant, for example to prevent humidity from rendering the dosage form unusable during storage.

[0109] The springs may be made of plastic or any elastic material, so that when the springs apply pressure to the support elements, they press the support elements against the capsule surface, thereby mechanically securing the capsule within the holding device. The support elements preferably have a shape complementary to the contour of the capsule, so that the contour of the capsule fits into the support elements.

[0110] In a preferred embodiment, the pharmaceutical dosage form comprises a pharmaceutical preparation to be applied to a mucous membrane, preferably the mucous membrane of the esophagus, and a capsule device comprising a weight, the preparation being connected to a retainer of an applicator configured to withdraw the preparation upon swallowing the dosage form, after which the retainer dissolves after a period of time in the mouth, the preparation adhering to the mucous membrane, particularly the esophagus, and the weight and capsule device dissolving in the stomach.

[0111] In a preferred embodiment, the pharmaceutical dosage form is manufactured, connected to a fixture, and loaded into an applicator by the following process steps.

[0112] In a first step, a capsule device is inserted into the machine using an insertion case, the capsule device including first and second half capsule shells joined by overlapping the first half capsule shell and the second half capsule shell at a joining position.

[0113] In a second step, the second half capsule shell is grasped by the insert case and separated from the first half capsule shell, and the applicator housing is placed in the machine.

[0114] In a third step, the piston moves the first half capsule shell toward the punch tool, so that the insertion pin of the punch tool enters the hollow, specifically the cylindrical hollow of the first half capsule shell, whereby the insertion pin holds the first half capsule shell, and thereby a part of the punch tool moving transversely to the movement direction of the insertion pin punches openings and / or recesses from the wall of the first half capsule shell.

[0115] In a fourth step, the insertion pin is pulled out of the hollow of the first half capsule shell. The first half capsule shell is positioned so that the punched opening preferably faces the applicator housing. The punching tool uses negative pressure to transport the material punched from the capsule wall out of the first half capsule shell.

[0116] In the fifth step, the preparation is clamped between two holding jaws and slightly stretched by increasing the distance between the two clamping jaws. On one side of one of the two holding jaws, the preparation extending beyond this holding jaw is cut flush with the holding jaw, thereby creating a cut end of the preparation while it is still stretched. This cut end of the preparation serves as the starting point for winding the preparation. A winding mandrel, i.e., a winding pin, is then threaded through the stretched preparation between the two jaws. One of the holding jaws used for cutting is then opened, as the end portion of the preparation is now also held by the winding mandrel. After or while the jaw is opened, the winding mandrel rotates so that the cut end of the preparation already clamped by the holding jaw is wound onto the winding mandrel, thereby creating the first winding.

[0117] In the sixth step, the other of the two holding jaws is opened and the winding mandrel rotates. In this process, additional preparation is wound onto the rotating winding mandrel. After a predetermined length of preparation is wound, the rotation of the winding mandrel stops. This length is preferably determined so that the end section of the preparation is not wound, i.e., the preparation is not completely rolled up. This end section of the preparation is used to connect the preparation to a fixture, i.e., to an end section of the fixture.

[0118] In a seventh step, the preparation wound on the winding mandrel is placed in front of the punched opening in the first half capsule shell. The wound preparation may partially protrude into the punched opening or recess. The unwound end section of the preparation is left outside the first half capsule shell.

[0119] In an eighth step, the winding mandrel is pulled from the rolled preparation and the rolled preparation is placed inside the first half capsule shell through the opening in the first half capsule shell by mechanically forcing the rolled preparation into the first half capsule shell through the opening.

[0120] In a ninth step, the insertion pin is moved into the hollow cylindrical opening of the first half capsule shell, and the rolled preparation placed in the first half capsule shell in step 8 is positioned deeper into the first half capsule shell. The end section of the unrolled preparation is placed in the coupling area of ​​the machine.

[0121] In a tenth step, the fastener is configured to be wrapped around the holding device of the applicator. Step 10 can also be performed simultaneously with, earlier than, or after other manufacturing steps. To wrap the fastener around the holding device, the fastener is mechanically secured to the machine by a clamping and cutting unit. The clamping and cutting unit includes clamping jaws between which the fastener can be clamped to apply tension to the fastener. The clamping and cutting unit further includes a cutter that cuts through the fastener and guide block to ensure a smooth cut of the fastener. In the tenth step, the fastener is tensioned by moving the clamping jaws.

[0122] In an eleventh step, the retainer is placed on a winding unit and placed alongside the tensioned fixture, and the fixture is attached to the wall structure of the retainer, so that when the retainer rotates, the fixture is wound onto the retainer.

[0123] In a twelfth step, one of the clamping jaws of the clamping and cutting unit is opened so that the fastener can be guided and slid through the clamping jaw for winding, while the other clamping jaw of the unit, which further includes a cutter, remains closed.

[0124] In a thirteenth step, the winding unit begins to rotate by rotating the clutch that secures and supports the holding device, thereby winding the holding device around the holding device. Ideally, the rotational motion is superimposed on a vertical translational motion, thereby winding the holding device around the holding device in a parallel position.

[0125] In step 14, after a predetermined length of the fastener has been wound around the holding device, the clamping jaws of the winding unit further tighten the fastener, so that the fastener remains clamped by the clamping jaws of the winding unit even when the cutter of the still-closed clamping jaws of the clamping and cutting unit cuts the fastener. The cutter then cuts the fastener. However, the fastener is not cut directly by the clamping jaws of the winding unit, but away from the unit. Thus, after cutting, a short section of the fastener remains outside the clamping jaws of the winding unit. This short section of the fastener is used to connect the fastener to a preparation in a further processing step. The winding unit further includes a robotic gripper.

[0126] In a fifteenth step, the robotic gripper of the winding unit transfers the holding device (with the fastener wound around it) and the fastener (clamped at one end by the clamp jaws of the winding unit) to the machine section on which the first capsule half shell is positioned and on which the applicator housing is placed. The robotic gripper positions the holding device on the axis by pushing it along the axis located within the housing. In doing so, the holding device is pushed along the axis to the extent that a short section of the fastener used to connect the fastener to the preparation can be positioned in a joining area located outside the housing. The joining area further includes an end section of the preparation. When both half shells are joined at the joining position and a gap is formed by the hollow cylindrical wall part, the end section extends through the opening of the first capsule half shell, i.e., through the gap of the capsule device.

[0127] In a sixteenth step, the fixture and / or the preparation is moistened, preferably by means of a spray nozzle. Moistening takes place in the bonding area.

[0128] In a seventeenth step, the fixation device is pressed against the preparation by means of a stamp to connect the preparation to the fixation device, the connection being made such that a tensile force can be transmitted between the fixation device and the preparation.

[0129] In step 18, weights are produced and inserted into the second half capsule shells. Step 18 can be performed simultaneously with, earlier than, or after other production steps. The weights are preferably pressed from powder using a press pin. A robotic rotating arm moves to the powder, picks up a predetermined amount of powder, and presses the powder. The robotic rotating arm then moves from the powder and rotates above the second half capsule shells. The pressed powder is preferably inserted directly into the second half capsule shells as weights. The step of producing the weights can be performed independently from other processing steps. That is, the weights can be produced prior to or in parallel with further processing steps, and the robotic arm can only grasp the pressed or otherwise produced weights. It is also contemplated that no weights are present in the capsule apparatus, and process step 18 can be omitted.

[0130] In a nineteenth step, the second capsule half shell is placed above the first capsule half shell using the insert case, with or without a weight. After the capsule halves are resting on top of each other, the second capsule half shell is pressed from the insert case onto or into the first capsule half shell, thereby forming a joining location. The end section of the preparation is unwound and extends from the opening into the joining area and is connected to the end section of the fastener.

[0131] In the twentieth step, a gap is formed by attaching a hollow cylindrical wall part to the first half capsule shell, and the first half capsule shell is connected to the second half capsule shell at a joining position. Alternatively, the gap is formed by attaching a hollow cylindrical wall part to both the first and second half capsule shells, so that the hollow cylindrical wall part covers both capsule halves when forming the gap. This has the advantage that the hollow cylindrical wall part further fixes the two capsule halves together, thereby mechanically stabilizing the capsule device.

[0132] In a twenty-first step, the capsule device formed in step 20 of the pharmaceutical dosage form is grasped using a grasping tool, positioned on a holding device, and placed within the holding device.

[0133] In a twenty-second step, the housing is pushed toward and onto the retainer. An end cap is placed on the housing, thereby closing the housing containing the retainer, now wrapped around the retainer, and the pharmaceutical dosage form disposed within the retainer, while connecting the end section of the retainer to the end section of the preparation, thereby completely unwinding the retainer and allowing the retainer to pull the preparation from the capsule device, for example, when the dosage form is swallowed by a patient.

[0134] Further preferred embodiments of the method for producing a pharmaceutical dosage form according to the present invention and further preferred embodiments of the method for producing a capsule device for a pharmaceutical dosage form according to the present invention can be understood from the description of the invention and its embodiments, as well as the description of the embodiments by means of the drawings.

[0135] Exemplary embodiments of the invention are described in more detail below with reference to the accompanying drawings and examples from which further features, advantages and embodiments can be learned. [Brief explanation of the drawings]

[0136] [Figure 1a] 1 shows a schematic side view of a dosage form according to a first embodiment of the present invention. [Figure 1b] Detail of the area marked "X" in FIG. 1a is shown. [Figure 1c] 1 shows an alternative configuration for the area marked "X" in FIG. 1a. [Figure 2a] FIG. 10 illustrates a top view of first and second half capsule shells aligned with one another to form a capsule device of a pharmaceutical dosage form according to another preferred embodiment of the present invention. [Figure 2b] FIG. 10 illustrates a top view of first and second half capsule shells aligned with one another to form a capsule device of a pharmaceutical dosage form according to another preferred embodiment of the present invention. [Figure 2c] 2b shows a top view of the first and second half capsule shells of FIG. 2a attached together along the direction of movement M. FIG. [Figure 2d] 2a shows a top view of a capsule device formed at the joining location of the first and second half capsule shells, with the second half capsule shell shown as transparent to indicate that an area of ​​the wall of the second half capsule shell partially overlaps with the opening. [Figure 2e] Corresponding to FIG. 2d, the first half capsule shell has a hollow cylindrical wall part which overlaps with the area of ​​the wall of the first half capsule shell shown by the dashed line, thereby forming a gap. [Figure 3a] FIG. 2b is a side view of the situation in FIG. 2a. [Figure 3b] 1 shows a pharmaceutical preparation in compressed form being inserted into the opening of a first half-capsule device, forming an exemplary step of a method according to the present invention for producing a pharmaceutical dosage form. [Figure 3c] 1 shows a pharmaceutical preparation in compressed form being inserted into the hollow space of the first half-capsule device, forming another exemplary step of a method according to the present invention for producing a pharmaceutical dosage form. [Figure 3d] 2d shows a pharmaceutical dosage form according to an embodiment of the present invention using the capsule device of FIG. [Figure 4a] 1 shows the first and second half capsule shells of a pharmaceutical preparation, and also shows a rotation axis X positioned within the opening to which a strip of preparation is connected, forming an exemplary step of a method according to the invention for producing a pharmaceutical dosage form. [Figure 4b] It is shown that the first and second half capsule shells of the pharmaceutical preparation according to Fig. 3d comprise an axis of rotation X which is located in the opening, and the strip-shaped preparation is partially wound around said axis by rotation (R), forming an exemplary step of the method according to the invention for producing a pharmaceutical dosage form. [Figure 4c] It is shown that the first and second half capsule shells of the pharmaceutical preparation according to Fig. 3d comprise an axis of rotation X which is located in the opening, and the strip-shaped preparation is completely wound around said axis by rotation (R), forming an exemplary step of the method according to the invention for producing a pharmaceutical dosage form. [Figure 4d] The second half capsule shell of the pharmaceutical preparation according to Figure 3d is shown to comprise a weight element inserted into the hollow space of the second half capsule shell, forming an exemplary step of a method according to the invention for producing a pharmaceutical dosage form. [Figure 5a] 1 illustrates the first step of using the kit to facilitate administration of the pharmaceutical dosage form before the patient swallows it. [Figure 5b] 1 illustrates a second step of using the kit to facilitate administration of the pharmaceutical dosage form after the patient has swallowed the dosage form. [Figure 6a] 1 illustrates steps of a method for attaching a retainer to a wall structure of a retention device in relation to a kit. [Figure 6b] 10 illustrates, in relation to a kit, steps in a method for wrapping a retainer around a retainer of an applicator after the retainer has been attached to the wall structure of the retainer. [Figure 6c] 1 illustrates steps of a method for connecting a securing device to a holding device of a preparation in relation to a kit. [Figure 6d] 1 illustrates, in relation to a kit, method steps for joining a first half capsule shell with a second half capsule shell while a retainer is connected to the preparation. [Figure 6e] 10 illustrates, in relation to the kit, steps in a method for assembling a capsule device to an applicator while a retainer is connected to the preparation. [Figure 7] 1 illustrates an end portion of the preparation connected to a retainer of the applicator. [Figure 8] It exemplarily shows a manufacturing machine according to the invention for producing pharmaceutical dosage forms according to the invention, in particular by carrying out a method according to the invention. [Figure 9a] 1 shows an exemplary mounting device of a manufacturing machine for mounting the preparation onto a first half capsule shell in a first step, in which the elongated preparation is wound up at a mounting position. [Figure 9b] 9a in a second step, where the elongated preparation is easily wound up and immediately cut by the cutting device. [Figure 9c] The mounting device of Figure 9b is exemplarily shown in a third step, in which, by actuation of the actuation device, the elongated preparation is easily wound up, cut from the storage roll, and inserted into the hollow space of the first half capsule shell through the opening. [Figure 10a] 1 shows a schematic cross section of an applicator with a pharmaceutical dosage form located within the bottom of the applicator holding device and covered by an applicator cap. [Figure 10b] 1 shows a schematic cross section of an applicator having a pharmaceutical dosage form disposed therein and a modified applicator cap. [Figure 11a] FIG. 10 shows a top view of first and second half capsule shells aligned with each other at a joint with a hollow cylindrical wall piece, thereby forming a capsule of a pharmaceutical dosage form according to another preferred embodiment of the present invention. [Figure 11b] 1 shows a top view of first and second half capsule shells aligned with each other at a joining position with a hollow cylindrical wall part, thereby forming a capsule device of a pharmaceutical dosage form according to another preferred embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0137] Figure 1a shows a capsule device 1 for application to the mucosa. The capsule device 1 has an elongated shape and contains a preparation 2 containing an active pharmaceutical ingredient. The preparation 2 is shown in a compressed state. Assuming that the preparation has a strip-like shape, Figure 1a shows a side view of the strip-like preparation wound as a spiral around an imaginary axis perpendicular to the drawing sheet. In the unfolded state, where the preparation is pulled out from the slit-like opening 5 of the capsule 3, the strip-like preparation 2 has the elongated shape of a substantially straight strip.

[0138] The capsule device 3 has a capsule shape and includes a hollow space 4. The hollow space 4 contains the preparation 2 in a compressed state. The capsule has a thin wall with a thickness of about 50 μm to 200 μm and is made of a biodegradable or non-biodegradable material.

[0139] The capsule device has a gap 5 that forms a planar curved slit. The width of the gap 5 formed as a curved slit is determined by measuring the distance between the opposing surface 5a of the capsule wall of the first half capsule shell 3a and the surface of the hollow cylindrical wall part 8a in a direction parallel to the longitudinal axis A. The distance "a" may be a constant value, for example, between 200 μm and 600 μm. The thickness t of the preparation may be a constant value, for example, between 20 μm and 150 μm.

[0140] With regard to the outer dimensions of the capsule device, for example, the height H of the capsule 3 may be 8 mm and the width W of the capsule may be 4 mm, although other dimensions of the capsule device are generally contemplated, taking into account the desired administration site on the patient.

[0141] A first end 2a of the preparation 2 extends through the gap 5 in the compressed state of the preparation, allowing the preparation to be grasped and pulled from the hollow space into the surrounding area of ​​the capsule device, thereby transitioning the preparation 2 from the compressed state to the expanded state. Pulling of the preparation, i.e., pulling action P (see FIG. 1b), may result from fixing end 2a of the preparation 2 and pulling the capsule device 3 in a direction M opposite to P. This is the case, for example, when using a process of administering the capsule device by swallowing the capsule device and connecting end 2a of the preparation to a fixing device of an applicator including a drinking cup, as shown in FIGS. 5a and 5b.

[0142] The first end 2a may have an end portion (see FIG. 1c) having a different shape than the strip 2. For example, the end portion may form a seal suitable for placement in the gap 5 to seal the gap 5 before the end portion is pulled out of the gap. Furthermore, the end portion may be configured to be connected to a retainer of the applicator by providing a bonding area.

[0143] FIG. 1b shows an enlarged view of the gap region 5. The gap 5 originates from the hollow cylindrical wall part 8, as shown in FIGS. 1a, 1b, and 1c, which is attached to the first half capsule shell 3a and overlaps with the opening 6 of the first half capsule shell 3a to form the slit-like gap 5. The slit-like gap 5 and the strip-like preparation 2 are dimensioned such that, when the preparation is pulled through the gap, a gap (S1, S2) is provided (measured at the gap cross section CS of the gap 5 between the preparation 2 and the surface 5a of the capsule device (S2) and between the preparation 2 and the surface of the hollow cylindrical wall part 8a (S1)), thereby defining the gap 5. Here, the central longitudinal axis A of the capsule extends parallel to the gap cross section CS. In the embodiment shown in FIG. 1, the surface of the capsule wall 5a is associated with the second half capsule shell 3b. However, the hollow cylindrical wall part 8 can also be positioned to some extent to be attached to the second half capsule shell 3b and accordingly provide a spacing (S1, S2) (measured at the gap cross section CS of the gap 5 between the preparation 2 and the surface 5a of the first half capsule shell of the capsule device (S2) and between the preparation 2 and the surface of the hollow cylindrical wall part 8a (S1)), thereby defining the gap 5.

[0144] The capsule device 3 shown in FIG. 1a includes a first half capsule shell 3a and a second half capsule shell 3b. The first half capsule shell 3a and the second half capsule shell 3b can be partially nested together to form the capsule device 3, or alternatively, the first and second half capsule shells can be aligned with each other without being nested together. When partially nested together, the opening 6 of the first half capsule shell 3a can be partially covered by the second half shell 3b. In embodiments where the opening is formed as a recess in the first half capsule shell, the second half capsule shell partially overlaps the recess in the first half capsule shell when they are partially nested together in a joint position. In embodiments where the opening is formed, for example, as a hole in the wall of the first half capsule shell, the second half capsule shell may or may not overlap the opening in the first half capsule shell. Such an opening 6 may be formed by milling the capsule material with a plate-shaped milling tool, such as a plate-shaped saw blade. In the embodiment shown in Figures 1a, 1b and 1c, the overlapping position, ie the joining position between the two half capsule shells 3a, 3b, is indicated by a dotted line marked with B.

[0145] As shown in FIG. 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 may be a constant value between 20 μm and 150 μm. The distance S=S1=S2 is measured by placing the preparation 2 in the center of the gap 5 and in a centered position on the surface of the strip parallel to and facing the surface 5a of the capsule and hollow cylindrical wall part 8a. While the preparation 2 is being pulled through the gap, the distance S may be present and, on average, be substantially constant. This means that it extends substantially along the entire length of the elongated preparation. However, the scope of the present invention may also encompass embodiments of dosage forms in which the distance between the preparation and the surface 5a (defining the gap) varies due to variations in the thickness t of the preparation 2, or the distance is partially blocked due to partial variations in the dimensions a and t (including partial dimensions a=t).

[0146] If the preparation has a string-like shape, the dimensions may be measured by analogy, and in the case of irregularly shaped preparations the dimensions may be determined by averaging.

[0147] As shown in FIG. 1c, first end 2a may have an end portion forming an enlarged section, which may be configured to prevent the preparation from being lost within capsule 3. This may make it easier for the patient or other interested party to pull the strip and retrieve end 2a to apply the dosage form in a predetermined manner. End portion 2a may also be configured to be placed in gap 5 to seal gap 5 before pulling end portion 2a out of the gap. Portion 7 may be provided on the end portion and configured to connect a wire, such as a retainer of an applicator, to end portion 2a. The width a' of gap 5, extending perpendicular to axis A and representing the elongated shape of capsule 3, is measured between opposing surfaces 5a' of the second half capsule shell. Width a' may be dimensioned the same as the width of preparation end portion 2a.

[0148] 2a shows a top view of a first half capsule shell 11 and a second half capsule shell 12 aligned to form a capsule device 13 of a pharmaceutical dosage form 10 according to another preferred embodiment of the present invention. The first half capsule shell 11 has a first end closed by a spheroidal cap 11a and a second end which is a hollow cylindrical wall 11b through which an opening is provided for the first half capsule shell 11. The second half capsule shell 12 has a first end closed by a spheroidal cap 12a and a second end which is a hollow cylindrical wall 12b through which an opening is provided for the second half capsule shell 12. The first half capsule shell 11 has a hollow cylindrical wall 11c that completely surrounds an opening 16. The opening 16 is essentially a hole in the wall 11c. Stability is provided by the wall frame 11c around the opening 16.

[0149] FIG. 2b shows a top view of a first half capsule shell 11' and a second half capsule shell 12' aligned to form a capsule device of a pharmaceutical dosage form according to another preferred embodiment of the present invention. The first half capsule shell 11' has a first end closed by a spheroidal cap 11a' and a second end which is a hollow cylindrical wall 11b' where the opening of the first half capsule shell 11' is provided. The second half capsule shell 12' has a first end closed by a spheroidal cap 12a' and a second end which is a hollow cylindrical wall 12b' where the opening of the second half capsule shell 12' is provided. The hollow cylindrical wall section 11c' does not completely surround the opening 16. Specifically, the opening 16 is formed as a recess 16' extending from the wall boundary of the second end 11b' toward the first end 11a'. The recess provides sufficient space within the hollow space of the first half capsule shell 11' for handling the preparation, in particular for inserting the preparation 2 in compressed form either along a direction perpendicular to the drawing plane and / or along the direction M.

[0150] 2c shows a top view of the first and second capsule half shells of FIG. 2a, fitted together along the direction of movement M, i.e., fitted together by a sliding motion. The cylindrical portion of the second capsule half shell 12 may have a slightly larger diameter than the cylindrical portion of the first capsule half shell 11 to facilitate engagement between the first and second capsule half shells 11, 12. The two halves 3a, 3b are pressed against each other until the compressed, i.e., rolled, preparation 2 can be easily inserted into the opening 6 of the first capsule half shell 3a, thereby defining a joining position. If necessary, the joining position can also be defined by slightly pressing the two halves 3, 3b against each other after inserting the compressed, i.e., rolled, preparation 2, so that it can no longer be removed from the opening 6.

[0151] FIG. 2d shows a top view of the capsule device 13 formed by joining the first and second half capsule shells 11 and 12 of FIG. 2a. As shown in FIG. 2d, the second half capsule shell is shown as transparent to illustrate that region 12c of wall 12b of the second half capsule shell overlaps with opening 16. As indicated by the arrow, opening 16, which remains open at the joining position, is partially covered by hollow cylindrical wall part 17, forming gap 15. Gap 15 is a slit extending partially circumferentially and partially tangentially around axis A in the capsule wall. The cross section A_o of the gap is significantly smaller than the cross section A_a of opening 16, for example by a factor f=0.05-0.2, i.e., A_o=f*A_a. In this way, the preparation inserted easily through the opening 16 at the joining point of the first half capsule shell 11 and the second half capsule shell 12 cannot come out of the gap 15 in the compressed state, but when it is unwound from the rolled state during swallowing (see Figure 5b), it can be easily pulled out of the gap 15 in the elongated position.

[0152] FIG. 2e corresponds to FIG. 2d, in which the first half capsule shell has a hollow cylindrical portion which overlaps with the area of ​​the wall of the first half capsule shell shown by the dashed line, thereby forming a gap.

[0153] Figure 3a shows a side view of the situation in Figure 2a. When projected on a plane, the opening 16 has a rectangular shape, but follows the cylindrical shape of the wall 11b in the circumferential direction. The opening 16 essentially opens the cylinder along approximately the entire width W (see Figure 1b), allowing the preparation in a compressed state to be inserted through the opening 16 into the hollow space 14 of the capsule device or of each of the first half capsule shells along a direction N perpendicular to the axis A (see Figure 3b).

[0154] FIG. 3 b shows the pharmaceutical preparation 2 in compressed form being inserted into the opening 16 of the first half capsule shell 11 .

[0155] FIG. 3c shows that the compressed form of the pharmaceutical preparation 2 is fully inserted into the hollow space 14 of the first half capsule shell 11, while the end 2a of the compressed form of the preparation extends through the opening 16 even as the second half capsule shell 12 moves into engagement with the first half capsule shell 11, thereby continuously reducing the free cross-section of the opening 16 until the joining position is reached.

[0156] Figure 3d shows a pharmaceutical dosage form 10 using the capsule device of Figure 2d. The gap is shown as transparent and is formed by a hollow cylindrical wall piece 17 that partially covers the opening 16.

[0157] FIG. 4a shows a first half capsule shell 11 and a second half capsule shell 12 of a pharmaceutical preparation, with an axis of rotation X positioned in the opening 16 and a strip of preparation 2 connected to axis X, forming an exemplary step of the method of manufacturing a capsule device and assembling a pharmaceutical dosage form according to the invention.

[0158] Figure 4b shows that the first half capsule shell 11 and the second half capsule shell 12 of the pharmaceutical preparation according to Figure 3d comprise an axis of rotation R, X, which is located in or in front of the opening, around which the strip-shaped preparation 2 is partially wound by rotation (R), forming an exemplary step of the method according to the invention for producing a capsule device and assembling a pharmaceutical dosage form. The direction of rotation (R) in Figure 4b is chosen by way of example and may therefore be opposite to the direction of rotation (R) shown.

[0159] Figure 4c shows that the first half capsule shell 11 and the second half capsule shell 12 of the pharmaceutical preparation according to Figure 3d comprise an axis of rotation X which is located in the opening, around which the strip-shaped preparation is completely wound by rotation (R), forming an exemplary step of the method according to the invention for manufacturing a capsule device and assembling a pharmaceutical dosage form.

[0160] Figure 4d shows that the second half capsule shell of the pharmaceutical preparation according to Figure 3d comprises a weight 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 manufacturing a capsule device and assembling a pharmaceutical dosage form.

[0161] 5a illustrates administration of a pharmaceutical dosage form comprising a capsule device, represented herein by a patient. A drinking cup 901 is filled with liquid and an applicator 902 is attached to the cup 901. The applicator 902 contains a pharmaceutical dosage form comprising a capsule device 903 and a retainer 904. The retainer 904 is connected to the preparation contained in the capsule device 903.

[0162] 5b illustrates the procedure when a patient swallows capsule device 903, which travels down the esophagus to the stomach. Retainer 904 pulls preparation 905 from capsule device 903. Preparation 905 then spreads along the esophagus, thereby delivering the active ingredient of preparation 905 to the esophageal mucosa.

[0163] Figure 6a shows a method for winding a fastener 101 around a holding device 102 of an applicator 103 by means of a machine 100. Thus, as shown in Figure 6a, in a first step of winding the fastener 101 around the holding device 102, the fastener 101 is mechanically fixed to the machine 100, which is equipped with a clamping and cutting unit 110. The cutting unit 110 comprises a clamping jaw 106, a cutter 108 and a guide means 107. In a second step, the fastener 101 is tensioned by moving the clamping jaw 106. In a third step, the holding device 102 is positioned along the tensioned fastener 101 by a material clutch 109 and the fastener 101, and is clamped in a groove in the wall structure of the holding device 102.

[0164] Figure 6b shows how the retainer is wrapped around the applicator's retainer after it has been attached to the retainer wall structure. In a first step, as shown in Figure 6b, the jaws 106 clamping the retainer 101 are opened.

[0165] In a second step, the holding device 102 is rotated by the winding unit, for example by rotating the clutch 109 that secures and supports the holding device 102, thereby winding the fastening device 101 around the holding device 102. The rotational movement is superimposed on a vertical translational movement, whereby the fastening device 101 is wound around the holding device 102 in a parallel position, while the clamp jaws re-secure the fastening device 101 in a sixth step after the fastening device has been fully wound around the holding device 102.

[0166] In a third step, a knife-like element 108 of the machine 100 cuts off one end of the fastener 101, which is then connected to the preparation 104 in a further step.

[0167] 6c shows a method for further assembling the kit by machine while connecting the fastener 101 to a holder of a preparation means that joins the fastener 101 with the preparation 104. In a first step, the positioning of the holder 102 over the opening 110 of the applicator housing 111 and the fastener 101 wrapped around the holder 102 is specifically performed by machine. The holder 102 is thus pressed by its opening 110 onto an axis 112, e.g., an auxiliary tube, so that the axis 112 extends through the housing 111 already positioned in the machine 100. The first half capsule shell 105a of the capsule device 105 is further positioned in the machine 100 and is placed next to the applicator housing 111, so that the preparation 104 extends at least partially from the first half 105a into the joining area 113 of the machine 100. The cut end 101a of the fastener 101 is further placed in the joining area 113 of the machine 100. The preparation 104 is then pulled from the capsule device 103 by the cut end 101a.

[0168] 6d illustrates a method for joining a first capsule half shell with a second capsule half shell while the retainer is connected to the preparation. As shown in the first step, the retainer end portion 101a is joined to one end of the preparation 104 in the clamping region 113. This causes the support 114 to move downward toward the joining region 113 and press against the overlapping preparation 104 and retainer end portion 101a. The joining is further illustrated in FIG. 10. In the second step, the second capsule half shell 105b is positioned above the first half 105a together with the weight element 115. In the third machine step, the two halves 105a, 105b are snapped, joined, or slid against each other, partially closing the opening and forming the joining position of the capsule device 105. In the fourth step, a hollow cylindrical wall part is attached to the capsule device, thereby forming a gap. The hollow cylindrical wall part can be attached to only the first half capsule shell or to the first half capsule shell and the second half capsule shell, i.e., so that both halves overlap. An end portion of the preparation 104 can be pulled out of the capsule device by the fixing device 101 through the gap in the capsule device.

[0169] Figure 6e relates to a method of assembling a capsule device to an applicator while the retainer is connected to the preparation. Accordingly, Figure 6e illustrates the steps of assembling a pharmaceutical dosage form, i.e., capsule device 105, comprising preparation 104, in the illustrated case, with applicator 103. Thus, in a first step, a gripping element 116, which holds capsule device 103, e.g., by negative pressure, is positioned above capsule device 103 to grip and transport capsule device 103 above housing 111 of applicator 105. In a second step, capsule device 103 is placed in housing 111. Housing 111 is further wrapped around retainer 102, as already described in connection with Figures 6c and 6d, to house retainer 101 positioned within opening 110 of housing 111. In a third step, housing 111 of applicator 105 is closed by end cap 117.

[0170] 7 shows an end portion of a preparation 701 connected to a retainer 702, for example, the end portion of a retainer of an applicator. In a first step, the retainer 702 is connected to the end portion of the preparation 701 by immersing the retainer in a pure water solution. In this embodiment, water acts as the adhesive. However, other embodiments are contemplated in which substances other than water can be used as the adhesive.

[0171] The fixture 702 is preferably immersed in the aqueous solution for a period of 1 to 10 seconds, 1 to 5 seconds, or about 1 second. In a second step, the immersed fixture 702 is positioned on the water-wetted end portion 701, such that the fixture 702 overlaps the end portion of the preparation 701 over an overlap distance d of 0.5 to 2 cm, 0.5 to 1.5 cm, or 0.5 to 1 cm, or preferably 1 cm. After positioning the fixture 702, the fixture 702 is pressed against the end portion of the preparation 701 while the end portion 701 is still wet with water. Pressing is preferably performed for a period of 1 to 10 seconds, 1 to 5 seconds, or 2 to 3 seconds. Pressing is performed using a contact pressure stamp. In a further third step, the joined fixture 702-preparation 701 is allowed to dry for a period of 1 to 10 minutes, 2 to 8 minutes, or preferably 5 minutes, before further processing of the joined parts. Alternatively, the fixture 702 is placed on the end portion 701 in a dry state without immersion, so that the fixture 702 overlaps the end portion of the preparation 701 over an overlap distance d, and then the fixture together with the end portion 701 is pressed against the fixture after pure water is sprayed. The spraying can be performed with the aid of a nozzle, such as a spray nozzle or atomizing nozzle, to atomize the liquid onto the surface to be sprayed. The nozzle facilitates dispersion of the liquid in the spray, thereby distributing the liquid over an area that includes at least the overlap distance d. Furthermore, the nozzle increases the liquid surface area, generating an inertial forward force on the solid surface.

[0172] FIG. 8 exemplarily illustrates a manufacturing machine according to the present invention for producing pharmaceutical dosage forms according to the present invention, particularly by performing the method according to the present invention. The manufacturing machine 200 is configured to manufacture pharmaceutical dosage forms according to the present invention by performing the method according to the present invention, and includes a positioning device 240 for positioning a first half capsule shell at an attachment position. The connecting device 260 has a movable element 261 configured to connect the second half capsule shell and the first half capsule shell at a joining position by moving the first half capsule shell 11, 11′ and the second half capsule shell 12, 12′ toward each other, so that the wall 12c of the second half capsule shell overlaps the cross-section of the opening 16, 16′ by an amount controlled by the movement of the movable element 261, thereby forming the capsule device 3, 13 at the joining position. Preferably, the connecting device 260 attaches a hollow cylindrical wall part to the joined capsule device 3, 13, thereby further assisting in forming the gap. However, an additional attachment unit may be provided to attach the hollow cylindrical wall part to the first half capsule shell or the first and second half capsule shells.

[0173] The positioning device 240 includes four holding members 243.1, 243.2, 243.3, and 243.4 that hold one or more of the first and / or second half capsule shells in place. The holding members provide a fixed space of a shape that secures the first and / or second half capsule shells by form-fitting. The holding members of the positioning device 240 may be configured to hold multiple first and / or second half capsule shells in place in parallel, where only one capsule is produced at each mounting position. In this way, the throughput of the manufacturing method can be increased. The positioning device 240 provides for the positioning of the four first and four second half capsule shells at four mounting positions, each provided by a holding member 243.1, 243.2, 243.3, and 243.4. This allows several manufacturing steps of the pharmaceutical dosage form to be performed in parallel using the multiple mounting positions, specifically, the work stations defined by the holding members.

[0174] The positioning device 240 comprises a rotatable platform 241 carrying work stations. Each work station comprises one holding member arranged along a radially outer region of the rotating platform. The movable platform 241 is rotatably arranged on a base member (not shown) that rotates about an axis 242 and is configured to rotate each work station to a work position of the machine. At a first work position (holding member 243.1 shown in FIG. 11 ), a feeder 251 is arranged to feed at least one first half capsule shell 11, 11′ to a mounting position provided by the holding member 243.1. At a second work position (holding member 243.2 shown in FIG. 11 ), a feeder 252 is arranged to feed a second half capsule shell 12, 12′ to a mounting position provided by the holding member 243.2.

[0175] In a third working position (retaining member 243.3 shown in FIG. 8) an attachment device 201 may be arranged for attaching the preparation 2, preferably in a compressed state, to the first half capsule shells 11, 11'. The attachment device 201 comprises a conveying device 220 for conveying the end portions 212a, 2a of the preparation to the attachment position, and a compression device 223.1, 223.2, in particular a winding device, for transferring the preparation 212,2 from an elongated state to a compressed state, in particular a folded or rolled state.

[0176] A fourth work position (shown in FIG. 8 as holding member 243.4) may be provided with a receiving station 270 for receiving already manufactured pharmaceutical dosage forms 10 and, in some cases, for storing or transferring the pharmaceutical dosage forms 10 to a conveyor system (not shown).

[0177] Preferably, the machine is provided with an electronic control device 280 for controlling the respective operations, which are performed automatically in the machine by controlling, in particular, the operation and parameters of at least one drive driving the rotation of the positioning device around axis 242, the supply of capsule portions by devices 252 and 251, the conveyance of the preparation by the conveying device, the operation of the compression device, in particular the rotation of the winding device, the cutting operation of the cutting device, the actuation operation of the actuating device, the connecting operation of the connecting device 260, and any further devices. The electronic control device 280 may comprise a user interface that allows a user to control the machine and / or the control software controlling the machine, in particular a computer program programmed to implement the respective steps of the method according to the invention, including all possible preferred steps described herein.

[0178] The manufacturing machine comprises a preparation storage device 210. The preparation storage device 210 provides a storage roll 212 of preparation. The preparation is released from the roll by rotating the roll 212 around an axis 211, thereby allowing the elongated preparation to be moved along a direction towards the cutting device 230 and the holding member 243.3. The holding member 243.3 provides a working position, and the movement of the elongated preparation 212 is guided by a guide unit 213 which also includes a roll 214. A portion 212a of the preparation 212 (which then forms the first end 2a of the elongated preparation 2) is gripped by a rotating shaft 223.1. The rotating shaft 223.1 is moved by rotating a rotating disk 222 about an axis R1 to its mounting position on the holding member 243.3. See FIG. 9a.

[0179] FIG. 9a shows an exemplary mounting device 201 of a manufacturing machine 200 for mounting the preparation 2 on the first half capsule shells 11, 11' in a first step, in which the elongate preparation 212 is wound up at the mounting location of the holding member 243.3.

[0180] The manufacturing machine 200 includes a conveying device 220 having an elongated shape and configured to convey an end of a preparation 212a containing an active pharmaceutical ingredient from a preparation storage position to a mounting position. The preparation is positioned to be inserted into the hollow space 14 of the first half capsule shell 11, 11'. The first half capsule shell 11, 11' is inserted at the mounting position 243.3, specifically through the opening 16. The conveying device includes a rotatable conveying member 222. The rotatable conveying member 222 is configured to receive at least a portion 212a of the preparation 212 at a first position 223.2, specifically after being released from the preparation storage device 210, and to convey the portion of the preparation 212a to the mounting position 243.3 by rotation R1. The movement or rotation of the conveying device 222 may be controlled by an electronic control unit 280 of the manufacturing machine 200.

[0181] The rotatable conveying member 222 may be provided with winding devices 223.1, 223.2 for winding the elongated preparation into a rolled state. The winding devices have two rotatable shafts 223.1, 223.2 that are electrically driven and configured to be controlled by the electronic control unit 280 of the manufacturing machine. The two rotatable shafts are arranged at positions offset from the rotation axis R1 of the rotatable conveying member 222. Specifically, when the rotatable shaft 223.1 is positioned in front of and within the opening 16, the rotatable conveying member 222 and / or the winding device are configured to wind the elongated preparation 212 at the attachment position 243.3, so that when the first half capsule shell is in the attachment position 243.3, the formation of the compressed preparation 2 takes place at the compression position in front of the opening and further within the opening 16 (thereby at least partially immediately inside the hollow space 14 of the first half capsule shell 11, 11′) as shown in Figures 9a and 9b. This significantly facilitates the transfer of the preparation into the capsule.

[0182] FIG. 9b exemplarily shows the mounting device 201 of FIG. 9a in a second step, where the elongated preparation 212 is easily wound up and immediately cut by the cutting device 230. In FIG.

[0183] The machine includes a cutting device 230 for cutting the preparation to form a preparation that is inserted into the hollow space of the first half capsule shell. The cutting device includes a first portion 231 having a first cutting edge and a second portion 232 having a second cutting edge.

[0184] Figure 9c exemplarily shows the mounting device 201 of Figure 9b in a third step, where, by actuation of an actuating device 233, which in this case is part of the second part 232, the elongated preparation 2 is easily wound up, cut from the storage roll 212 and inserted into the hollow space 14 of the first half capsule shell 11 through the opening 16. The manufacturing machine comprises an actuating device 233 which moves the compressed preparation 2 from the compressed position to its final position within the hollow space 14 of the first half capsule shell 11.

[0185] 10a shows a schematic cross-section of an applicator 1000 including a pharmaceutical dosage form 1002, with a preparation 1013 disposed within the bottom 1005 of an applicator holding device 1007, covered by an applicator cap 1003 including a lid 1004. The bottom 1005 is shown with a dotted line separating it from the top, i.e., cap 1003, although both parts form the housing 1006 of the applicator 1000. The dosage form 1002 is disposed within the housing 1006, specifically within the holding device 1007. The dosage form 1002 is therefore disposed within the holding device 1007 vertically, thus along an axis that defines its elongated shape. The holding device 1007 comprises a rod 1007a, which extends along the dosage form 1002 and serves to support the dosage form 1002, i.e., capsule device, in a vertical position within the holding device structure 1007. Retainer 1008 is wrapped around rod 1007a. Weight element 1009 is further housed within dosage form 1002. The rod structure of retainer 1007 allows dosage form 1002 to move vertically as indicated by the arrow.

[0186] Figure 10b shows a schematic cross section of the applicator shown in Figure 10a. To prevent vertical movement of the dosage form 1002 in the event that the applicator 1000 is inverted or vibrated, a curved retainer 1010 is placed on the spherically shaped cap of the dosage form 1002. Therefore, the retainer 1010 preferably has an external contour similar to that of the end cap of the dosage form 1002. Furthermore, the retainer 1010 is secured by a spring 1011. The spring 1011 also presses the retainer 1010 against the cap of the dosage form 1002. Therefore, the dosage form 1002 cannot move vertically. Furthermore, the lid 1004 of the applicator 1000 contains a desiccant 1012 to prevent the dosage form 1002 from becoming unusable.

[0187] Both Figures 11a and 11b schematically illustrate a view of a capsule device 13 having a first half capsule shell 11, 11' and a second half capsule shell 12, which are fitted together in a joining position to form the capsule device 13. The overlapping areas between the two half shells 11, 11', 12, and 12' are indicated by dotted lines. In Figure 11a, the first half capsule shell 11' includes an opening 16 formed in the capsule wall in the shape of a slit. The opening 16 can be punched into the capsule half 11' by a punching machine. If the opening in the capsule wall material is created by a punching tool, the punched capsule wall material can be transported from the capsule by a suction device. Ideally, the suction device is integrated into the punching tool, for example, by vacuum suction. The second half shell 12 is slid onto the first half shell 11' to form a joining position. In the joining position, the second half shell 12 does not overlap the first half shell 11', ultimately forming a gap 15. The hollow cylindrical wall part 17' is a wall part made of, for example, a capsule material adapted to the external geometry of the halves 11' and closes the opening 16' of the half shells 11' like a patch so that a gap 15 is formed. In the embodiment shown in FIG. 11a, the opening 16 of the first half capsule shell is formed as a recess, and the hollow cylindrical wall part 17 overlaps the first half capsule shell 11 and the second half capsule shell 12, with the gap 15 being formed in the first half capsule shell 11. In this embodiment, it is preferred that both the first and second half capsule shells include the hollow cylindrical wall part 17. In an alternative embodiment not shown, the hollow cylindrical wall part 17 preferably overlaps only the first half capsule shell 11. The gap 15 is formed essentially at the joining location where the second half capsule shell terminates, so that preferably only the first half capsule shell includes a hollow cylindrical wall part.

[0188] Figure 11b shows a configuration similar to that shown in Figure 11a. The opening 16 in the first capsule half 11 is formed as a hole 16 in the wall of the capsule half 11, rather than as a slit. The hole 16 is preferably formed as an elongated hole 16. A hollow cylindrical wall part 17 covers the opening 15 of the first capsule half 11 like a patch, so that a gap 15 is formed. In the embodiment shown in Figure 11a, the hollow cylindrical wall part 17 preferably overlaps only the first half capsule shell 11, while the second half capsule shell 12 is preferably left intact, with the gap 15 being formed essentially at the joint where the second half capsule shell terminates. In this embodiment, preferably only the first half capsule shell includes the hollow cylindrical wall part 17. In an alternative embodiment not shown, the hollow cylindrical wall part 17 overlaps the first half capsule shell 11 and the second half capsule shell 12, and a gap 15 is formed in the first half capsule shell 11, whereby the first half capsule shell and the second half capsule shell 12 comprise hollow cylindrical wall parts.

[0189] In the embodiment shown in Figures 11a and 11b, the capsule device 13, as an example of all embodiments, further comprises a small flag 18, e.g., a disassemblable adhesive strip, which serves to mechanically connect the two capsule halves 11, 12 at the connection location to form the capsule device 13. [Explanation of symbols]

[0190] Figures 1a to 1c 1. Drug dosage form 2 Preparations 2a End portion of the preparation 3 Capsule device 3a First half capsule shell 3b Second half capsule shell 4 Hollow space 5. Gap 5a Capsule wall surface 6. Opening of first half capsule shell 7. Part of the edge of the preparation 8. Hollow cylindrical wall parts 8a Surface of hollow cylindrical wall part 2a to 2e, 3a to 3d, 4a to 4d, 11a, and 11b 10 Pharmaceutical dosage forms 11 First half capsule shell 11a Spherical Cap 11b Hollow cylindrical wall 11c Capsule Wall 11d Capsule wall area 12 Second half capsule shell 12a spheroid cap 12b Hollow cylindrical wall 12c Capsule wall area 13 Capsule Device 14 Hollow space 15 Gap 16 Opening 17 Hollow cylindrical wall parts 18 small flag 60 Weight Elements Figure 5a, Figure 5b 901 Drinking Cup 902 Applicator 903 Capsule Device 904 Fixtures 905 Preparations Figures 6a to 6e 100 machines 101 Fixtures 101a End portion of fixing device 102 Applicator holder 105a First half capsule shell 105b Second half capsule shell 106 Clamp Jaw 107 Guidance means 108 Cutter 109 Support Clutch 110 Cutting Unit 111 applicator housing 112 axis 113 Combined area 114 Support 115 Weight Element 116 Gripping element 117 End Cap Figure 7 701 Preparations 702 Fixtures Figures 8 and 9a to 9c 200 manufacturing machine 201 Installation equipment 210 Storage device 211 axis 212 Preparation storage roll 212a End portion of preparation 213 Guidance Unit 214 rolls 220 Transport equipment 222 Rotating Disk 223.1 Compression equipment 223.2 Compression equipment 230 Cutting device 231 First part of cutting device 232 Second part of cutting device having cutting edge 233 Actuator 240 Positioning Device 241 Rotatable Platform 242 axis 243.1 Retaining members 243.2 Retaining members 243.3 Retaining members 243.4 Retaining members 251 Feeding device 251 Equipment 252 Equipment 260 Connection Device 261 Moving Elements 270 Pick-up Station 280 Control Device Figure 10a, Figure 10b 1000 Applicators 1002 Pharmaceutical dosage forms 1003 Applicator Cap 1004 Lid 1005 Bottom of applicator 1006 Case 1007 Holding device 1008 Fixtures 1009 Weight element 1010 Curved retainer 1011 Spring 1012 Desiccant 1013 Condiments

Claims

1. A capsule device (13) adapted to be applied to a mucous membrane, having an elongated shape, containing a pharmaceutical preparation (2) containing an active pharmaceutical ingredient, and capable of being placed in a compressed state and an expanded state, a hollow space (14) for containing the preparation (2) in the compressed state, a gap (15) configured to allow a first end (2 a) of the preparation in the compressed state to extend through the gap (15), thereby allowing the preparation to transition from the compressed state within the hollow space (14) to the expanded state in the surrounding area of ​​the capsule device (13); The capsule assembly comprises a first half capsule shell (11, 11') and a second half capsule shell (12), the first half capsule shell (11, 11') and the second half capsule shell (12) being joined by overlapping the first half capsule shell (11, 11') and the second half capsule shell (12) at a joining position; The capsule device (13) further comprises a hollow cylindrical wall part (17, 17'), the first half capsule shell (11, 11') having a hollow cylindrical wall (11c, 11c') including an opening (16, 16'), and the hollow cylindrical wall part (17, 17') overlaps with a cross section of the opening (16, 16'), thereby forming the gap (15) of the capsule device (13) at the joining position.

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

3. 2. The capsule device according to claim 1, wherein the hollow cylindrical wall (11c') of the first half capsule shell (11) is closed at a first end (11a) and open at a second end (11b), and the opening (16') is formed as a recess starting from the second end (11b) and extending toward the first end (11a).

4. 4. The capsule device according to claim 1, wherein the cross section of the opening (16, 16') is dimensioned to accommodate the preparation (2) in the compressed state before joining the first half capsule shell (11, 11') and the second half capsule shell (12, 12'), and in the joining position, the gap (15) defined by the opening (16) and the hollow cylindrical wall part (17, 17') has a cross section dimensioned to prevent the preparation (2) in the compressed state from passing through the gap (15).

5. The capsule device according to any one of claims 1 to 3, wherein the cross-sectional size of the gap (15) is a fraction f of the cross-sectional size A_a of the opening (16, 16'), where A_o = f * A_a, and 0.0010 < f < 0.7500.

6. The capsule device according to any one of claims 1 to 3, wherein in the joining position, the first half capsule shell (11, 11') is inserted into the second half capsule shell (12, 12').

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

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

9. The capsule device of any one of claims 1 to 3, further comprising a weight device (60) occupying a portion of the hollow space and providing additional weight to the capsule device.

10. A capsule device described in any one of claims 1 to 3, wherein the mucosa is a buccal or gastrointestinal mucosa.

11. The capsule device of claim 10, wherein the gastrointestinal mucosa is the esophageal mucosa.

12. A method (100) for manufacturing a capsule device (1, 10, 51) for containing a pharmaceutical preparation according to claim 1, comprising: a) providing the first half capsule shell (11, 11') and the 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') into the joining position to provide the hollow cylindrical wall part that overlaps with the cross section of the opening (16, 16'), thereby forming the gap (15) of the capsule device (13) at the joining position.

13. The step a) further comprises: a) providing materials for forming the capsule device (13), specifically the first half capsule shell and the second half capsule shell; b) creating an opening (16, 16'), in particular a rectangular opening (16, 16'), in the material of the first half capsule shell and / or the second half capsule shell.

14. 14. The method according to claim 13, wherein the openings (16, 16') are created in the material of the formed hollow cylindrical wall of the first half capsule shell and / or the second half capsule shell.

15. A pharmaceutical dosage form comprising a capsule device (13) according to claim 1 and a pharmaceutical preparation (2) having an elongated shape, containing an active pharmaceutical ingredient and capable of being placed in a compressed state and in an expanded state.

16. A method for producing a pharmaceutical dosage form according to claim 15, comprising a method for producing a capsule device (13) according to claim 12, a) providing said preparation having an elongated shape and comprising an active pharmaceutical ingredient; b) providing the first and second half capsule shells having hollow cylindrical walls including openings (16, 16'); c) compressing the preparation into the first half capsule shell through the opening (16, 16') so that a portion or end of the preparation extends through the opening (16, 16'); d) sliding the second half capsule shell (12, 12') and the first half capsule shell (11, 11') into the joining position to provide the hollow cylindrical wall parts (17, 17') that overlap the cross section of the opening (16, 16'), thereby forming the gap (15) of the capsule device (13) at the joining position.

17. 17. The method according to claim 16, further comprising providing a rotation axis (X) after step a) or step b), positioning said rotation axis (X) in front of or within the cross section of said opening (16, 16'), and rotating said rotation axis until said preparation reaches a compressed state, thereby winding said preparation in an elongated state using said opening (16, 16') to guide and / or align said preparation.

18. 17. The method of claim 16, further comprising, after step b) or step c), disposing a weight device in at least a portion of the hollow space of the first half capsule shell and / or the second half capsule shell.

19. 16. A kit comprising the pharmaceutical dosage form of claim 15, a drinking cup, and an applicator for administering the pharmaceutical dosage form to a patient, the applicator being in fluid communication with the drinking cup and containing the pharmaceutical dosage form, the preparation of the pharmaceutical dosage form being connected to the applicator by a retainer for withdrawing the preparation from the capsule device after administration to the patient.

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