Method and apparatus for the manufacture of pharmaceutical dosage forms

Abstract

The invention relates to a method for manufacturing a pharmaceutical dosage form, comprising the following steps: a) Provision of at least one first active ingredient and / or excipient, wherein this is formed as a thread (2), b) Feeding the thread (2) from step a) to a drive shaft (5, 8) via at least one feed nozzle (4), c) Applying the thread (2) from step b) to the drive shaft (5, 8) or inserting the thread (2) into a recess on the drive shaft (5, 8), d) Rotation of the drive shaft (5, 8) and translational and / or oscillating movements of the at least one feed nozzle (4) relative to the drive shaft (5, 8), such that the thread (2) from step c) forms turns, wherein the individual turns are not parallel to each other and a body of revolution (1, 16, 22) is generated from the thread (2), wherein its size is determined by the rotation frequency of the drive shaft (5, 8), the diameter of the drive shaft (5, 8) and the total rotation time of the drive shaft (5, 8), e) Pulling the body of revolution (1, 16, 22) produced in step d) away from the drive shaft (5, 8) so that a pharmaceutical dosage form is obtained.

Description

[0001] The present invention relates to a method and a device for the production of individualized, in particular oral, dosage forms. Application area

[0002] A classic method for producing individualized oral dosage forms is the manual filling of capsules with powdered active ingredients and excipients. Pharmacies use capsule filling machines for this manual process.

[0003] For pharmaceutical dosage forms manufactured industrially in large quantities, dosage can be achieved by varying the administration intervals. Mechanical division of dosage forms is a common approach to achieve a degree of individualization.

[0004] The production of pharmaceutical dosage forms using additive manufacturing processes such as 3D printing opens up possibilities for highly precise, patient-specific dosing.

[0005] The application of 3D printing in pharmaceuticals offers numerous advantages: Personalized dosage: Medications can be individually tailored to the patient's needs, which is particularly advantageous in the case of specific dosage requirements or combination therapies. Complex release profiles: By precisely controlling the tablet structure, different release mechanisms can be implemented to control the timing of drug release. Fast dissolution: The porous structure of the 3D-printed tablets allows for faster dissolution in the mouth, making them easier for patients to take. In addition to an individualized dose of the active ingredient, an individualized adjustment of the release rate is desirable. This is particularly advantageous for elderly people with specific pharmacokinetics. State of the art

[0006] Common additive manufacturing processes for producing individualized oral dosage forms include selective laser sintering (SLS), fused deposition melting (FDM), or melt extrusion deposition (MED).

[0007] 3D printing by melt extrusion (MED) is an additive manufacturing technology in which powdered raw materials are continuously softened / melted and then precisely applied layer by layer. This allows for the production of tablets with specific geometric structures.

[0008] Currently, the epilepsy medication Spritam is the only 3D-printed drug with market approval. The development goal was not individualization, but rather to formulate a drug that disintegrates quickly in the mouth and contains high concentrations of the active ingredient. The drug is manufactured using Zip Dose technology, in which powder particles are built up layer by layer in a 3D printer using a powder binding process and then bonded together.

[0009] Several patent applications propose solutions for the production of tablets using additive manufacturing processes. Examples include: • EP1582191B1 Kit for manufacturing a dosage form for dispensing a bioactive substance • EP2313050B1 A system and method for manufacturing a medication • US20230131161A1 System and method for producing pharmaceutical objects via 3d printing • WO 2016038356 Solid dosage form production • EP3911303A1 Method for the production of a solid dosage form and solid dosage form • US11622940B2 Solid forms and methods of preparing the same • EP2456427B1 Hot melt extruded sustained-release pharmaceutical dosage form Disadvantages of the state of the art

[0010] In the production of tablets using additive manufacturing processes, solid bodies are printed. The active ingredients are bound in excipients and are released in the stomach or intestines.

[0011] To increase the solubility of active ingredients, the surface area from which they are released can be increased. To overcome some of the solubility and disintegration problems of 3D-printed solid dosage forms, US patent 11622940 proposes a solution in which the solid, printed tablet form has one or more channels, generally in the form of tubular passages or grooves, through the printed body. A disadvantage of this method is that if the perforations in the body are too large or too numerous, the dosage forms lose stability.

[0012] Spritam is the first FDA-approved 3D-printed tablet. It is a medication for the treatment of epilepsy. These tablets are "printed" layer by layer, with each layer being bonded with a liquid. All 3D-printed tablets dissolve very easily, which is particularly beneficial for patients with swallowing difficulties, as the tablet dissolves in the mouth. These porous dosage forms dissolve too quickly to deliver active ingredients to the gastrointestinal tract.

[0013] Printing tablets using fused deposition modeling (FDM) requires melting the filament. The active ingredients must be sufficiently thermostable at the necessary melting temperature to prevent degradation during the manufacturing process. Printing liquid, semi-solid, or porous active ingredients and excipients is not possible.

[0014] Fluctuating drug release is a potential problem with printed tablets, as the layer-by-layer manufacturing process can lead to uneven porosity. This can make the timing and rate of drug release unpredictable.

[0015] If the tablet is printed too densely, this can slow down the dissolution, while tablets that are too porous can cause a release that is too rapid.

[0016] The targeted parameterization of release profiles presents a challenge: Difficult to reproduce: The rate at which the active ingredient is released depends on the printing parameters (e.g., layer thickness, amount of binder). Small deviations in the printing process can cause large differences in the release of the active ingredient. Problems with controlled release: Targeted control of drug release (e.g., delayed or pulsating release) is complex and requires precise adjustments to the printing process.

[0017] Furthermore, the temperature and pressure sensitivity of the active ingredients limits their use for 3D printing of tablets: Degradation by heat: Processes such as fused deposition modeling (FDM) expose materials to high temperatures, which can degrade heat-sensitive active ingredients.

[0018] Altered crystal structure: Some pharmaceutical agents can change their crystal structure due to pressure or temperature, which can affect their solubility and bioavailability.

[0019] The limited compatibility of excipients is also a challenge for 3D tablet printing: Lack of standardization: Conventional tablets contain specially developed excipients to control release, which are not always suitable for 3D printing.

[0020] Difficulties with delayed-release formulations: Many conventional polymers used for delayed release cannot be easily processed in 3D printing.

[0021] Depending on the printing method used, fluctuations in drug release can occur, or even undesirable reactions can occur, as explained here using two common printing methods for tablets: Binder jetting: This method can lead to uneven wetting and thus inconsistent drug release. Fused Deposition Modeling (FDM): Here, incomplete fusion of layers can create undesirable variability in drug release. Stereolithography (SLA): The use of photopolymers can lead to undesirable chemical reactions with the active ingredient. Additive manufacturing processes build objects sequentially. Parallelization could only be achieved with considerable effort by mounting multiple printheads on a common printhead carrier and then printing in parallel. However, this solution is very complex for printing filaments with different active ingredients into a single tablet, as the filament must be changed or multiple printheads must be used simultaneously.

[0022] The additive manufacturing processes listed above produce solid formulations. To produce individualized, oral dosage forms with liquid active ingredients, only the binder jetting process is practically feasible. However, this method has the disadvantage of resulting in highly porous dosage forms. In the case of the aforementioned application of the medication for the treatment of epilepsy, rapid availability of the active ingredient through absorption via the oral mucosa was desired.

[0023] This solution is not suitable for delivering liquid or powdered active ingredients to the gastrointestinal tract and for controlling the targeted release of the active ingredient. Object of the invention

[0024] The object of the invention is to produce a pharmaceutical dosage form from essentially solid excipients and / or solid, pasty or liquid active ingredients.

[0025] Another task is to be able to process active ingredients into individualized dosage forms with low or no thermal stress.

[0026] Furthermore, the invention aims to make the manufacturing process of such pharmaceutical dosage forms parallelizable, so that higher productivity can be achieved compared to sequential manufacturing using typical additive processes. Explanations of terms used Thread: Here, a thread is understood to be a thin strand of active ingredients and excipients. This is preferably produced and processed directly from filament using a nozzle with small nozzle diameters – typically in the range of 0.1 to 0.5 mm. The cross-section of a strand is typically round. However, it can have a rectangular shape, for example, when manufactured from thin sheets (with a height similar to the aforementioned nozzle diameters) that are cut into thin strips. Dosage form: A dosage form (also called galenic form) is the specific way in which a drug is prepared to combine an active ingredient and excipients into a ready-to-use medication. It determines how the drug is administered and how it interacts with the body. Solids of revolution: Solids of revolution are structures made up of coils of threads. In one design, the coils of threads are built up layer by layer, non-parallel to each other, with an intersection angle typically of 5 to 90 degrees. Semi-solid active ingredients and excipients: Semi-solid and pasty forms of medicinal products include, in particular, gels, ointments, creams and pastes. Gel: A gel usually consists of a swellable scaffold and a liquid. Drug substances can be incorporated into this base. Cream: A cream is a soft, spreadable preparation with a high water content. Ointments: Ointments are spreadable medicinal preparations, usually based on fat. Pastes: Pastes are ointments that have a high solids content. Adhesive: An adhesive, also called glue, is a non-metallic process material that bonds other materials together through surface adhesion and its own strength (cohesion). Binders: Binders are substances that establish or promote chemical bonds at the phase boundaries of other substances, or that trigger or enhance effects such as cohesion, adsorption, adhesion, and friction. They join substances by absorbing, attaching, holding together, cross-linking, or bonding them. Powdered substance: Powdered substances are powders. Powders are dispersed systems consisting of a solid and a gaseous phase. The solid phase consists of finely dispersed particles that appear macroscopically as clumps. The individual particles differ in shape, mass, and surface area. Cohesive forces hold them together. Solution to the task

[0027] The problem is solved by a manufacturing process in which a body of revolution 1, 16, 22 is constructed from at least one thread 2. The size of the body of revolution 1, 16, 22 is variable and its size and shape are adapted to common oral dosage forms such as tablets, capsules, caplets, softgels, chewable tablets, and the like. The body of revolution 1, 16, 22 can also be used for other application methods, particularly vaginal and rectal administration.

[0028] The solution comprises a method and apparatus and the fabrication of bodies of revolution 1, 16, 22 as described in Fig. 1 and Fig. 2 are shown schematically.

[0029] Variants of the solution for producing bodies of revolution 1, 16, and 22 differ in whether a core is used (bodies of revolution 16) around which the threads are wound, or whether no core is used (bodies of revolution 1). Furthermore, the solution variants differ with regard to the active ingredients and excipients used. Alternatively, the body of revolution can be produced filled with powder (bodies of revolution 22). Description of methods according to the invention for the production of a pharmaceutical dosage form

[0030] The inventive method for producing a pharmaceutical dosage form comprises at least the following steps: a) Provision of at least one first active ingredient and / or excipient, wherein this is formed as thread 2 b) Feeding the thread 2 from step a) to a drive shaft 5 via at least one feed nozzle 4 c) Applying the thread 2 from step b) to the drive shaft 5 or inserting the thread 2 into a recess on the drive shaft 5 d) Rotation of the drive shaft 5 and translational and / or oscillating movements of the at least one feed nozzle 4 relative to the drive shaft 5, such that the thread 2 from step c) in which individual turns are not parallel to each other, wherein a body of revolution 1, 16, 22 is generated from the thread 2, the size of which is determined by the rotation frequency of the drive shaft 5, the diameter of the drive shaft 5 and the total rotation time e) Pulling the body of revolution 1, 16, 22 produced in step d) away from the drive shaft 5, so that a pharmaceutical dosage form.

[0031] Customization is preferably achieved by specifying the rotational frequency of the drive shaft and the total rotational time. Alternatively or additionally, the diameter of the drive shaft 5 can also be changed to achieve customization. Fig. Figure 3 illustrates the step-by-step construction of winding layers.

[0032] Because the windings of the threads are not parallel, a stable solid of revolution 1 without a core is formed. Depending on the winding density, a desired solubility behavior of the dosage form can be adjusted.

[0033] Alternatively, in process step d), at least one feed nozzle 4 can rotate around a stationary driver and perform the translational or oscillating movements.

[0034] Excipients should dissolve in the gastrointestinal tract, allowing the active ingredients to be released and absorbed by the body. Examples of such excipients include hydroxypropylcellulose, hydroxypropylmethylcellulose, ethylcellulose, Eudragit, or Kollidon, used individually or preferably in combination. Stearic acid, used as a plasticizer, adjusts the elasticity of the fibers so that they are well-suited for the production of revolution bodies.

[0035] The adhesion of the windings of thread 2 to each other can be achieved by gluing, joining with suitable binders or joining under the influence of temperature.

[0036] A first alternative embodiment of the method according to the invention comprises the thread having a coating of adhesive which leads to the windings sticking together.

[0037] The first alternative embodiment of the method according to the invention comprises an additional process step a1) which takes place after step a) and before step b). In step a1), the thread 2 is coated with a binder. For this purpose, it is, for example, drawn through a solution containing at least one binder. Examples of binders are starch, sugar, and cellulose derivatives.

[0038] In a second alternative embodiment, in step d) during rotation, one or more binding agents are additionally added to join the turns of the thread 2. This can be combined with the first alternative embodiment of the method according to the invention.

[0039] In a third alternative embodiment, the windings of the thread 2 are joined under the influence of heat. The necessary temperature for joining under the influence of heat is achieved by heating the thread 2. In an additional process step d1), the rotating body 1, 16, 22 is heated until the necessary temperature for bonding the individual windings of the thread 2 is reached. This step d1) takes place during process step d) or between process step d) and process step e). The temperature required for bonding the individual windings of the thread 2 is material-dependent and is based on material-specific properties such as the glass transition temperature of polymers.

[0040] A fourth alternative embodiment of the method according to the invention serves to produce a body of revolution 16 with a core made of active and / or auxiliary materials.

[0041] The core can be formed from at least one solid or liquid active ingredient and / or excipient. The core is completely or partially enclosed by the filament 2. Depending on the winding density, a desired solubility behavior can be achieved with these configurations as well.

[0042] In step a), at least one additional active ingredient and / or excipient, which is liquid, is provided.

[0043] Furthermore, in a fourth alternative embodiment, a process step b0) takes place between process step a) and process step b), in which a droplet 10 is first formed from the at least one additional active ingredient and / or excipient. For this purpose, the at least one additional active ingredient and / or excipient is, for example, pressed through a further drive shaft 8. This shaft is hollow. The droplet size is preferably determined by selecting the diameter of the passage through the drive shaft 8. The desired quantity of active ingredient and / or excipient can be adjusted by using different droplet sizes. The droplet 10 is fixed to the drive shaft 8 so that it can retain its shape until it is wrapped by the thread 2. This fixing can consist of cooling the droplet 10 until it is sufficiently stable. The selected temperature depends on the material.This could be, for example, the freezing point, a specific temperature to achieve the desired viscosity, or the glass transition temperature.

[0044] The process is shown in the figure. Fig. 4 schematically illustrated.

[0045] Step by step, thread turns are wound around the droplet 10 as the core. In step d), the drive shaft 5 rotates with the thread 2 around the droplet 10.

[0046] The thread 2 can consist purely of excipients or contain one or more active ingredients. In this way, bodies of revolution 16 with combinations of active ingredients can be produced.

[0047] Solid core: In a fifth alternative embodiment, at least one additional active ingredient and / or excipient is provided in step a), which is in the form of a solid.

[0048] The encapsulation of at least one further active ingredient and / or excipient, which is in the form of a solid and serves as the core 13 of the dosage form, is achieved by preceding process step b) with a process step b1), in which at least one further active ingredient and / or excipient is fixed onto a further drive shaft 8. Fixation is preferably achieved by suction. Then, in step d), the drive shaft 5 rotates with the thread 2 around the core 13.

[0049] Fig. Figure 5 schematically shows the process steps for encapsulating solid cores.

[0050] Depending on the desired solubility, the core can be completely encapsulated from the second active ingredient or excipient, or the coils can be so permeable that the stomach acid can act directly on the core and release the active ingredients.

[0051] A sixth alternative embodiment of the method according to the invention serves to produce a rotating body 22 with powder filling for encapsulating powdered active ingredients and / or excipients.

[0052] To encapsulate powdered substances in such a way that they can be swallowed and subsequently release the active ingredient in the gastrointestinal tract, a dense or partially dense capsule is built up layer by layer and filled with a powdered substance 21 during the construction process. This powdered substance 21 comprises at least one further active ingredient and / or excipient. The materials used in this process can have both primary pharmacological effects and also exhibit shape-determining or release-modulating properties.

[0053] Examples of commonly used powdered active ingredients that are typically filled into capsules include: • Antibiotics, such as amoxicillin, ciprofloxacin or doxycycline • Antidepressants, such as sertraline, fluoxetine or amitriptyline • Antihypertensive drugs: such as lisinopril, amlodipine or losartan

[0054] These active ingredients are used in various therapeutic areas and can be formulated in capsules to ensure targeted release and better bioavailability.

[0055] The embodiment for producing bodies of revolution 22 for encasing powdered substances comprises at least the following additional steps: In step a), in addition to providing the thread 2, at least one powdered substance 21 is provided. In step d) the drive shaft 5 is rotated and the at least one feed nozzle 4 is moved translationally and / or oscillatingly relative to the drive shaft 5, such that a body of revolution in the form of a hollow shell 20 is first produced from the thread 2 and then, at the end of this step, a closed hollow sphere.

[0056] Additionally, during step d), a step d1) is performed. In this step, the body of revolution 22 is filled with the powdered substance 21 from step a).

[0057] The illustration Fig. Figure 6 shows the process steps for the production of bodies of revolution filled with powdered substance.

[0058] A seventh alternative embodiment of the method according to the invention serves to produce bodies of revolution 1, 16, 22 from filament or granules.

[0059] This involves melting a filament or granules and drawing the melt into a thin thread, which is then used to produce bodies of revolution.

[0060] The inventive method for producing bodies of revolution from filament or granules comprises the following process steps o1 to o3, which take place before step a): o1) Provision of filament or granules containing at least one active ingredient and / or excipient o2) Heat the filament or granules from step o1) until they melt. o3) Generating a thread 2 from the melted filament or granules from step o2). This can be done, for example, by extrusion.

[0061] An eighth alternative embodiment of the method according to the invention serves as a method for producing bodies of revolution 1, 16, 22 from a thread 2 which is additionally enriched with at least a second liquid or gaseous active and / or auxiliary substance.

[0062] This embodiment provides that the thread 2 made from the first active ingredient and / or excipient is drawn through a bath with liquid active ingredients or through a chamber with nebulized or gaseous active ingredients before the thread 2 is processed into a body of rotation 1, 16, 22.

[0063] In this alternative embodiment of the method according to the invention, an additional process step a1) is performed after step a) and before step b). In step a1), the thread 2 is enriched with the second active ingredient and / or excipient. For this purpose, the thread 2 is drawn through an enrichment chamber. This is preferably a bath containing a liquid that includes the second active ingredient and / or excipient, or a chamber containing a gas or aerosol that includes the second active ingredient and / or excipient. The materials used in this process can have both primary pharmacological effects and also possess shape-forming or release-modulating properties.

[0064] An example of an active ingredient that is liquid at room temperature and exhibits good compatibility in polymers as the base material of thread 2 is ibuprofen.

[0065] Description of device designs for carrying out the described process steps.

[0066] A device for carrying out the method according to the invention comprises at least one stationary receiving punch 32 and a drive unit for the at least one feed nozzle 4, which serves to convey a thread 2. The feed nozzle 4 is movably arranged non-aligned with the receiving punch 32 such that the thread 2 is conveyed through the feed nozzle 4 towards the receiving punch 32 and can adhere to it or be mechanically gripped, so that a rotating body 1, 16, 22 can be built up from turns of the thread 2 by a combination of a rotational movement of the feed nozzle 4 around the receiving punch 32 and a translational and / or arc-shaped movement of the feed nozzle 4.

[0067] Fig. 7, Fig. 8 to Fig. Figure 9 illustrates the schematic structure of such a device. One or more feed nozzles 4 are driven such that their movement leads to the construction of one or more rotating bodies 1, 16, 22 from turns of one or more threads.

[0068] Feed nozzles 4, which guide a thread of matching diameter to the drive shaft 5, 8, comprise a propulsion unit of driven rotating shafts, between which the thread 2 is conveyed forward towards the nozzle outlet due to friction.

[0069] Feed nozzles 4, which process filament 25 consisting of at least one additive and / or excipient, additionally comprise a heating element, so that the filament 25 is melted and forced through the nozzle opening. The nozzle opening preferably has an opening cross-section of 0.1–0.5 mm. Thus, the filament 2 is forced out of the at least one feed nozzle 4 and guided to the drive shaft 5, 8.

[0070] Devices for encapsulating at least one liquid active ingredient and / or excipient have a hollow drive shaft 8, through which the liquid active ingredients and / or excipients can be forced. A droplet 10 forms at the end of the hollow drive shaft 8, which is then enveloped by the thread 2 in coils. With such a device, a body of revolution 16 can be produced, the core of which comprises at least one liquid active ingredient and excipient.

[0071] In a device for encapsulating at least one solid active and / or auxiliary substance, the drive shaft 5, 8 is designed such that a core 13 is formed, which is preferably fixed by negative pressure, so that a filled body of revolution 16 can then be produced by wrapping it with the thread 2.

[0072] In devices for encapsulating a powdered substance 21, the drive shaft 5, 8 is designed such that a hollow shell 20 is first formed by the thread 2, which is then further built up to a hollow sphere and is filled with the powder. Detailed description of exemplary embodiments: Production of a body of revolution without a core

[0073] In Fig. Figure 3 schematically illustrates the process of manufacturing a body of revolution 1. The drive shaft 5 is shown in its initial state at the top. In the next step, a first turn of thread 2 is wound onto the drive shaft 5. The subsequent steps schematically show how further turns are successively applied until a stable body of revolution 1 has been formed. The feed nozzle 4 performs a circular segment-forming or translational movement. Fig. Figure 3 shows the first winding 6 of a thread 2 and a partially completed body of revolution 7. Production of a body of revolution with a core made of liquid active ingredients and / or excipients

[0074] Fig. Figure 4 schematically shows how liquid substances are forced through a drive shaft 8 and a droplet 10 forms. In the following steps, this droplet 10 is wrapped with a thread 2 until it is partially, largely, or completely encapsulated. For this purpose, the liquid substances are guided through the feed channel 9 and the drive shaft 8, so that a liquid droplet 10 forms at the end of the drive shaft 8. This droplet 10 is preferably cooled until it can be wrapped with thread windings. Figure 4 further shows... Fig. 4 in process step 11 a partially wrapped drop and in process step 12 a fully wrapped drop. Production of a body of revolution with a core made of solid active ingredients and / or excipients

[0075] Fig. Figure 5 shows the encapsulation of solids. A solid 13 with at least one active ingredient and / or auxiliary substance forms the core of a rotating body 16. The rotating holder 14 is preferably designed as a hollow shaft, so that the solid 13 can be drawn in and thus held by the holder 14 for the subsequent process steps.

[0076] The solid body 13 is wrapped in stages. This wrapping process can continue until the solid body 13 is completely wrapped. To also cover the area used for suction fixation, another rotating holder 15 is inserted, which suctions and fixes the rotating body 16. After rotating the holding device consisting of holders 14 and 15, holder 15 takes over the fixation and further rotation of the rotating body 16, so that the remaining exposed area of ​​this rotating body 16 can be closed. At the end of the process, a rotating body 16 is produced that encloses a solid core 13.

[0077] For other applications, incomplete wrapping can be advantageous, as it increases the solubility of the active ingredients from the core. The solubility can thus be adjusted by varying the winding density. Since the filament used for wrapping can also contain active ingredients, a dosage form with multiple active ingredients can be produced in this way. A sustained-release formulation is therefore easy to manufacture. Production of a body of revolution with a core made of powdered substance

[0078] Fig. Figure 6 schematically shows how powdered substances 21 are encapsulated. First, a lower hollow shell 20 is built up layer by layer on the rotating base die 18. This is then filled with the powdered substance 21 via a filling tube 19. The rotating body 22 is then built up layer by layer until a closed rotating body 22, formed by coils and filled with the powdered substance 21, is created. The powdered substance 21 comprises at least one active ingredient or excipient.

[0079] The filling and assembly of the bodies of revolution 22 can be carried out in parallel. Depending on the winding density, the solubility behavior can therefore also be adjusted in this configuration.

[0080] In this formulation, powdered active ingredients and / or excipients are advantageously used, which are employed in pharmacies for the manual production of capsules using capsule filling machines. Examples of powdered excipients include, for example, the DiluCapa capsule fillers from Fagron GmbH. Devices with one or more feed nozzles 4

[0081] Fig. Figure 7 shows a drive shaft 5, which is driven by a motor 23. A feed nozzle 4 feeds the thread 2 with at least one active ingredient and / or excipient in such a way that the thread becomes fixed to the drive shaft 5. The rotation of the drive shaft 5 and the translational movement of the feed nozzle 4 form a rotating body 1. The drive shaft 5 can be roughened or forked at its end to improve thread engagement.

[0082] Fig. Figure 8 shows a design similar to Fig. 7, however, with a device 24 having three feed nozzles 4. In the simplest case, the feed nozzles 4 are mechanically coupled. Separate deflections are also possible.

[0083] In Fig. Figure 9 shows an embodiment in which a filament 25 containing at least one active ingredient and / or excipient is inserted into a nozzle with a feed device 26. The filament 25 is conveyed into a heating element 27 and melted there. The melt is then forced through a nozzle opening with the desired filament diameter. A filament 2 is formed, which is then further processed as in the described process steps to build a body of revolution 1, 16, 22. Devices for enriching a thread 2 with at least one active ingredient

[0084] Fig. Figure 10 shows a spool 28 from which a thread 2 containing at least one active ingredient and / or excipient is unwound. The thread 2 is drawn through a trough containing a liquid 30 enriched with at least one active ingredient. This transforms the thread 2 into an impregnated thread 29. The impregnated thread 29 is then conveyed by means of a feed nozzle 4 to the device for constructing a rotating body.

[0085] Fig. Figure 11 shows an embodiment in which a thread 2, consisting of at least one excipient and / or active ingredient, is drawn through a chamber 31. The active ingredients are present in the chamber 31 in gaseous, nebulized, or aerosol form. This transforms the thread 2 into an impregnated thread 29. The impregnated thread 29 is then conveyed to the device for constructing a rotating body by means of a feed nozzle 4.

[0086] Fig. Figure 12 schematically shows a device with a stationary receiving punch 32 around which a feed nozzle 4 performs a combination of a rotational movement around the receiving punch 32 and a translational and / or arc-shaped movement, so that a rotating body 1, 16, 22 can also be constructed from coils. Description of illustrations

[0087] The following description of the illustrations shown serves to explain the invention. It shows: Fig. 1 a schematic representation of a solid of revolution 1. Fig. Figure 2 shows a schematic representation of a solid of revolution 1, which consists of coils of two different threads (2, 3). To distinguish them, thread 2 is shown as a solid line and the other thread 3 as a dashed line. Fig. 3 process steps for the step-by-step construction of a coreless body of revolution 1 Fig. 4 process steps for the step-by-step construction of a body of revolution 16 around a droplet 10 as a core. Fig. 5 process steps for the step-by-step construction of a body of revolution 16 around a solid core 13. Fig. 6 process steps for the step-by-step construction of a body of revolution 22 with a powdered filling. Fig. 7 a side view of a driven drive shaft and at least one feed nozzle 4. Fig. 8 a side view of a driven drive shaft 5 and three feed nozzles 4. Fig. 9 a cross-section of a nozzle. Fig. 10 a schematic representation of the enrichment of a thread 2 in a liquid bath. Fig. 11 a schematic representation of the enrichment of a thread 2 in a chamber with gaseous or nebulized active substances. Fig. 12 a device with a fixed receiving punch 32.

[0088] In Fig. 3, Fig. 4 to Fig. In figure 5, the feed nozzle 4 is only shown in the first process step to improve clarity. List of reference symbols: 1. Solids of revolution 2. first thread containing at least one active ingredient and / or excipient 3. further thread with at least one active ingredient and / or excipient 4. Feed nozzle (cross-section) 5. Drive shaft (with axis of rotation A) 6. First winding of a thread 2 7. Partially completed body of revolution 8. Hollow drive shaft (sectional view) 9. Feed channel through the drive shaft 10. Drops containing active ingredients and / or excipients 11th process step with partially wrapped droplet 12th process step with wrapped droplet 13. Solid core with at least one active ingredient and / or excipient 14. rotating holder 15. Holder as counterpart to the rotating holder 14 16. filled solid of revolution with a core 18. rotating base stamp 19. Filling pipe 20. Hollow shell made of interconnected windings 21. Powder containing at least one active ingredient and / or excipient 22. Filled rotating body with powder filling 23. Motor for driving the drive shaft 5 24. Device with three feed nozzles 25. Filament made of at least one excipient and / or active ingredient 26. Nozzle with feed device 27. Heating element 28. Roll with a thread made of at least one excipient and / or active ingredient 29. Thread made of at least one excipient and / or active ingredient 30. Liquid containing active ingredients 31. Chamber containing gaseous or nebulized active ingredients 32. Admission stamp

Claims

A method for manufacturing a pharmaceutical dosage form, comprising the following steps: a) providing at least one first active ingredient and / or excipient, wherein this is designed as a thread (2); b) feeding the thread (2) from step a) to a drive shaft (5, 8) via at least one feed nozzle (4); c) applying the thread (2) from step b) to the drive shaft (5, 8) or inserting the thread (2) into a recess on the drive shaft (5, 8); d) rotating the drive shaft (5, 8) and translational and / or oscillating movements of the at least one feed nozzle (4) relative to the drive shaft (5, 8), such that the thread (2) from step c) forms turns, wherein the individual turns are not parallel to each other and a body of revolution (1, 16, 22) is produced from the thread (2), the size of which depends on the rotational frequency of the drive shaft (5, 8), the diameter of the drive shaft (5, 8) and the total rotation time of the drive shaft (5, 8) is determined,e) Pulling the body of revolution (1, 16, 22) produced in step d) off the drive shaft (5, 8) so that a pharmaceutical dosage form is obtained. Method for manufacturing a pharmaceutical dosage form according to claim 1, characterized in that it further comprises a step a1) which is carried out after step a) and before step b), wherein in step a1) the thread from step a) is coated with an adhesive. Method for producing a pharmaceutical dosage form according to claim 1, characterized in that step d) additionally comprises the addition of a binder for joining the turns of the thread (2). Method for producing a pharmaceutical dosage form according to claim 1, characterized in that the rotating body (1, 16, 22) is heated in an additional process step d1) until the necessary temperature to bond the individual turns of the thread is reached, wherein step d1) is carried out during the rotation in step d) or between the rotation d) and the peeling in step e). A method for producing a pharmaceutical dosage form according to at least one of the preceding claims 1 to 4, characterized in that: • in process step a) at least one additional active ingredient and / or excipient is provided, which is liquid; • between process step a) and process step b) a process step b0) is carried out, in which at least one drop (10) is formed from the at least one second active ingredient and / or excipient and the drop (10) is fixed to the drive shaft (8) so that it can retain its shape until it is wrapped by the thread (2); • in step d) the thread (2) from step c) is wrapped around the drop (10) from step b0) so that a filled body of revolution (16) is produced. A method for manufacturing a pharmaceutical dosage form, according to at least one of claims 1 to 4, characterized in that: • in process step a) at least one core (13) made of at least one second active ingredient and / or excipient, which is in the form of a solid, is additionally provided; • between process step a) and process step b) a process step b1) is carried out in which the core (13) is fixed on a drive shaft (5, 8); and • in step d) the thread (2) from step c) is wound around the core (13) from step b1) so that a filled body of revolution (16) is produced. A method for producing a pharmaceutical dosage form according to at least one of the preceding claims 1 to 4, characterized in that: • in step a) at least one powder (21) with at least one second active ingredient and / or excipient is additionally provided; • in step d) the rotation of the drive shaft (5) and the translational and / or oscillating movements of the at least one feed nozzle (4) relative to the drive shaft (5) are carried out in such a way that a body of revolution in the form of a hollow shell (20) is first produced from the thread (2) and then, upon completion of this step, a closed hollow sphere as a body of revolution (22) is produced; and furthermore, • during step d), a step d1) is carried out in which the body of revolution (22) is filled with the powder (21) from step a). Method for producing a pharmaceutical dosage form according to claim 7, characterized in that after step d1) and before step e) step d) is repeated so that a capsule shell is produced from further turns of the thread (2) around the rotating body (22). A method for manufacturing a pharmaceutical dosage form according to at least one of the preceding claims 1 to 8, wherein, prior to step a), the following steps are carried out: o1) provision of at least one first active ingredient and / or excipient, wherein this is in the form of granules or filament, o2) heating the filament or granules from step o1) until it melts, o3) generating the thread (2) from the melted filament or granules from step o2) for provision in step a). Method for the manufacture of a pharmaceutical dosage form according to at least one of the preceding claims 1 to 9, wherein the method comprises an additional process step a2) which is carried out after step a) and before step b), wherein in step a2) the thread (2) is impregnated with at least one further active substance and / or excipient. Device for carrying out a method according to one of claims 1 to 10 comprising at least one rotatable drive shaft (5, 8), at least one feed nozzle (4) for conveying the thread (2), a drive unit for the at least one feed nozzle (4), characterized in that the at least one feed nozzle (4) is arranged non-aligned with the drive shaft (5, 8) so that the thread (2) can be conveyed through the feed nozzle (4) to the drive shaft (5, 8) and can adhere to it or be mechanically gripped, so that by a combination of the rotation of the drive shaft (5, 8) and the translational and / or oscillating movements of the at least one feed nozzle (4) relative to the drive shaft (5, 8) a rotating body (1, 16, 22) can be built up from turns of the thread (2) in order to produce a pharmaceutical dosage form.

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