EP2977195A1 - Apparatus and method of manufacturing multiple-layer tablets - Google Patents

Abstract

The invention relates to a device (10, 11) for producing multilayer tablets (200, 201) from solid starting materials (210, 211, 212, 213), in particular from powders, granules and / or from geometrically limited intermediates (220, 221, 222 , 223), comprising a plurality of processing stations (100) and a conveyor unit (50, 60) with a plurality of conveyor containers (51, 61), wherein the individual processing stations (100) are modularly variable in their arrangement. Furthermore, multilayer tablets (200, 201) which can be produced with a device (10, 11) according to the invention and methods for producing multilayer tablets (200, 201) are also provided within the scope of the invention.

Description

The invention relates to a device for producing multilayer tablets from solid starting materials, in particular from powders, granules and / or from geometrically limited intermediates, comprising a plurality of processing stations and a conveyor unit with a plurality of conveyor containers. Furthermore, within the scope of the invention, multilayer tablets are also disclosed, which are produced using a device according to the invention, as well as process variants for the production of multilayer tablets.

Different variants for the production of multilayer tablets are known from the prior art. The term "multilayer tablet" as used hereinafter generally refers to solid bodies which have multiple layers of powders, granules and / or of geometrically limited intermediates, such as single-layered tablets, which are joined together in one unit. Thus, among multi-layer tablets within the scope of the invention in addition to pharmaceutical tablets, which are provided for oral use or as soluble effervescent tablets, so-called cleaning rod, as used for example for dishwashers or for cleaning dentures ("third teeth"), and various Dietary supplements in tablet form to understand.

Usually, in the production of multilayer tablets, two or more layers of different starting materials, for example granules or powders, are compressed into one unit. For this purpose, for example, rotary presses are used with at least two filling and pressing stations. The pressing process usually proceeds as follows: The granules or powder, which forms a first tablet layer, is thereby filled into a die and compacted by a press die under a relatively low pressure. Thereafter, this part is lowered in the die by moving the lower punch to a lower position and filling the powder or granules of the second layer above it. Finally, this layer and the two layers are compacted with the full pressing force. The filling takes place from different Füllschuhen with appropriate storage containers. As an alternative, the granules can also be successively filled into the matrix and pressed in a single step.

Primarily, so-called rotary tableting machines or rotary presses are used in which both punches are moved against each other. One disadvantage of the known tabletting machines is that for pressing multi-layered or multi-layered tablets, usually high pressing forces are required, which often leads to undesirable positional displacements of the individual tablet layers or tablet layers relative to one another and thus to an increased proportion of reject production during the pressing process.

Furthermore, it is disadvantageous that the currently known tableting machines are each set for a specific production process and assembled accordingly. A simple retrofitting of existing tableting machines to produce if necessary new or changed products is usually not possible or requires at least a high conversion costs, including the associated conversion costs and uneconomically long downtime until a correspondingly upgraded tabletting machine can be put into operation again , Which is why the purchase of a tailor-made, new tableting machine was usually the only economic alternative to the production of new or modified multi-layer tablets. In particular, in the production of small series of multilayer tablets, for example as prototypes in the context of clinical research programs, the lack of flexibility or lack of opportunity for rapid and cost-effective conversion of existing tabletting machines is particularly disturbing.

The design of multilayer tablets with known from the prior art tableting machines is subject to restrictions. Thus, in conventional tabletting machines, the possible layer thicknesses depend on the fineness of the granulation or a particle size of the powder particles and on the design of the tablet press. Currently standard layer thicknesses are at least 1 mm, which is why with conventional tableting usually not more than three layers are pressed together.

Furthermore, it is currently required in the known devices that the starting materials or intermediates to be pressed are each dry or at least have only a very low moisture content. In addition, the use of problematic starting materials such as lubricants, which have a lubricating effect on the rotary plate of known rotary tableting machines, must be avoided as far as possible in the currently known tabletting machines. Likewise, granules that break easily under a compressive load, with conventional Tableting machines at the currently usual, high pressing pressures, which are usually between 5 kN and 20 kN, but also presses are used with a main pressure of up to 200 kN, are not processed.

Moreover, it is known from the prior art that it can come after the compression of different powders, granules and / or of geometrically limited intermediates with each other for layered detachment of compressed mass of the produced compact. This detachment process, in which the individual compressed layers of a multilayer tablet usually separate again after a relatively long time, is referred to as "capping" - or in English as "capping".

Furthermore, in multi-layer tablets currently known from the state of the art, it should be noted that undesirable reactions or undesired mutual influence may occur within the multilayer tablet between different starting materials and / or active substances in adjoining layers.

It is therefore an object of the present invention to provide a device for producing multilayer tablets of solid starting materials, which avoids the disadvantages of the prior art.

This object is achieved with a device according to the preamble of claim 1 having the features of the characterizing part of claim 1. The subclaims relate to further particularly advantageous embodiments of the invention.

In a device according to the invention for producing multilayer tablets from solid starting materials, in particular from powders, granules and / or from geometrically limited intermediates, comprising a plurality of processing stations and a conveyor unit with a plurality of conveyor containers, the individual processing stations are modularly variable in their arrangement.

A number and / or a sequence of the processing stations is or are modularly variable in a production device according to the invention. Thus, it is possible, one and the same inventive device quickly and with relatively little effort and in a short set-up time by modular variation of the correspondingly required processing stations, for example, from the production of two-layer tablets on the production of three or multi-layer tablets retrofit. Due to the advantageous separation The sequence and the number of process steps can be variably set for the respective process steps in individual processing stations. Thus, a manufacturing device according to the invention can be used particularly flexible for the production of a variety of multilayer tablets.

For example, multilayer tablets with different contours in oval, circular and / or in square or square shape can be produced with the same device after appropriate adaptation. Likewise, in the production according to the invention, various bonding agents may be used which, depending on the nature or property of the selected bonding agent, may also each have different processing methods for applying the bonding agents to powder, granules and / or geometrically limited intermediates, for example by spraying, dripping, etc., require. For this purpose, the respectively required processing stations are selected and, if necessary, arranged in a corresponding sequence or individual processing stations are correspondingly replaced by other processing stations. Thus, it is possible to produce different products with the same or optionally suitably adapted arrangement of the processing stations with one and the same device.

Another advantage of the modularly variable arrangement of the processing stations is that a device according to the invention can be used with the same basic structure for the production of various products from different industrial sectors. For example, with a device of the same basic construction, it is possible to produce both multilayer tablets for pharmaceutical applications and, for example, cleansing tablets which are used for cleaning purposes for dishwashers or for cleaning dentures, or else dietary supplements in tablet form.

In addition, the novel, modular variable arrangement of the individual processing stations in a device according to the invention has the advantage that individual processing stations, if necessary, can be maintained separately or renewed. Thus, in a device according to the invention, the costs for service and maintenance are advantageously lower than is the case in currently known from the prior art machines for tablet production. The coupling of individual processing stations with other external units and devices within a process chain is facilitated by the modular arrangement of the device according to the invention. Thus, individual processing stations or even the Integrate entire device according to the invention particularly simple and flexible in existing processes and facilities of a complex manufacturing process. For example, already existing packaging machines, loading stations and / or unloading stations can be flexibly coupled to the corresponding processing stations of the device according to the invention.

In a device according to the invention, the multiple processing stations are particularly advantageously arranged serially along a substantially linear processing path. In this embodiment, the processing stations required in each case for producing an individual multilayer tablet are arranged in a particularly compact and clearly arranged linear manner. Thus, the sequence of the individual manufacturing steps can also be monitored very easily. Due to the clear arrangement and easy accessibility monitoring of quality parameters of current production, for example, with external monitoring devices is particularly comfortable possible in a device according to the invention in addition to monitoring of incoming or outgoing materials. Likewise, monitoring devices for monitoring quality parameters of ongoing production, in particular for monitoring flow, mass or weight, density, temperature and / or composition can be provided within the scope of the device according to the invention. If necessary, external monitoring devices, measuring devices, analyzers, sensors, etc. can be used and coupled with the corresponding processing stations or integrated into them.

Required changes in the sequence and / or number of processing stations along the substantially linear processing path are also easy to accomplish.

In a particularly expedient embodiment, in a device according to the invention, the several processing stations are arranged serially along a curved processing path, preferably along a closed curved processing path. This variant has the advantage of a particularly compact, space-saving arrangement of the processing stations. Furthermore, this arrangement is particularly advantageous for manufacturing processes in which an at least partially multiple passage of individual processing stations or a repetition of certain processing steps is required. If necessary, the delivery unit or the corresponding delivery containers can be moved several times in a circle along the curved processing path over an entire revolution in order to pass through individual processing stations several times.

Alternatively or in addition, it is within the scope of the invention further possible for multiple repetition of a particular processing step, for example, the processing step of connecting at least two tablet layers together at appropriate positions along the processing path, the corresponding same processing station, for example, here a composite station for connecting the Tablets layers, provide at appropriate locations several times in succession.

Depending on the space requirement or space available, the closed curved processing paths can have, for example, a circular or elliptical shape.

In one development of the invention, in one device, the processing stations are arranged in one plane, preferably in a substantially horizontal plane. The arrangement of the processing stations in a plane also underlines advantages of the modular construction of the devices according to the invention. When retrofitting the device between different production methods, an optionally required change of individual processing stations is particularly easy due to their arrangement in a common plane, preferably in a common horizontal plane.

Suitably, in a device according to the invention for the production of multilayer tablets, at least one of the processing stations is repeatedly passable. A multilayer tablet or its starting materials and / or their geometrically limited intermediates and / or their multilayer tablet body passes through or pass through at least one of the processing stations of the device according to the invention several times. Advantageously, the device can be made compact in this embodiment and operated particularly economically. In this embodiment, for example, multilayer tablets having more than two layers connected to one another can be produced by a plurality of circulations or runs, even with a device prepared for producing a two-layer tablet. Thus, for example, six-layered multilayer tablets can be produced by passing through the corresponding processing stations three times with a device which is in itself prepared for producing a two-layered tablet.

In a device according to the invention, a plurality of solid starting materials and / or a plurality of geometrically limited intermediates can advantageously be processed simultaneously in a processing station. Depending on the requirement, individual can thus be used Processing stations are also arranged parallel to each other and / or fed in parallel. This is particularly useful for processing stations for individual manufacturing steps with a comparatively long processing time.

In a preferred embodiment of the invention, in a device of the conveyor unit in a production cycle, the solid starting materials and / or the geometrically limited intermediates can be transferred from a previous processing station to a subsequent processing station in the transport direction. For the transfer of a preceding to a subsequent processing station, the conveyor unit with the corresponding conveyor containers.

Suitably remain in a device according to the invention, the solid starting materials and / or the geometrically limited intermediates at least between two adjacent processing stations within their respective delivery container. Depending on the individual manufacturing process, it is possible within the scope of the invention to carry out production steps in individual processing stations in each case directly in the delivery container. For example, it is conceivable that a processing step in which a starting material is pressed and compacted as powder or granulate into a geometrically limited intermediate product is carried out within the corresponding delivery container, which for example has a female mold with the contours of the intermediate product.

It is also provided within the scope of the invention that, if necessary, intermediates and / or tablet body removed from the respective conveyor and fed to a corresponding processing station for performing the respective processing step, then after the processing step again the same delivery container or another delivery container or fed to this to be handed over. Likewise, it is possible within the scope of the invention for mixed forms of the two abovementioned regimes to be carried out within a device according to the invention or a production method. Thus, if appropriate, with the device according to the invention, individual processing steps can be carried out directly on the media respectively within the conveying container, while for other processing steps the substances or substance mixtures are removed from the conveying containers and the following treatment and / or processing then outside Delivery container takes place in the respective processing stations. In a device according to the invention, it is particularly expedient to provide at least one application station for applying at least one bonding agent to a solid starting material and / or a geometrically limited intermediate product. By using one or more connecting agents which are applied to a starting material or an intermediate product, for example a starting material already compacted into a tablet compact or a multilayer tablet body, the otherwise usually required high pressing pressures for pressing the tablets or their components can be significantly reduced become.

Due to the lower pressing pressures required when using corresponding connecting means, unwanted layer displacement and / or breakage of individual layers in the production of multilayer tablets is reduced or avoided, and thus the reject rate of multilayer tablets which are broken or deformed during production is advantageously reduced. Advantageously, multilayer tablets with a greater number of interconnected layers or with layers having lower layer thicknesses can be produced by the use of connecting agents and the lower tablet pressures required for tablet production. For example, layer thicknesses of bonding agents that are applied between individual layers of powders, granules and / or geometrically limited intermediates may be a few nanometers or micrometers. It is likewise provided within the scope of the invention, depending on the requirement, to realize multilayer tablets having layer thicknesses - in the micrometer range or millimeter range, depending on the powders, granules and / or geometrically limited intermediates used.

In a device according to the invention, in the at least one application station for applying bonding agent to a solid starting material and / or a geometrically limited intermediate, it is particularly advantageous to use female molds with receiving bores with an undersize within which female molds the geometrically limited intermediate products are inserted and glued together. By using appropriate Matrizenformen a particularly accurate, displacement-free positioning of the individual tablet layers is ensured during bonding.

Suitable binders are in themselves all known from the prior art binders in question, which improve the cohesion in the starting materials, for example in powders or granules or in the geometrically limited intermediates and thus increase the overall strength of the tablets.

If necessary, the use of lubricants in multi-layer tablets is also made possible by the use of appropriate connecting means, since adequate bonding between the individual layers, despite the lubricants used, is ensured by the connecting means used. For example, metallic stearates, which are usually problematic as a lubricant in tablet production, can also be used in multi-layer tablets consolidated with bonding agents.

One or more connecting means can also be applied in the production of a multilayer tablet such that the connecting medium layer acts as a separating layer between two adjacent layers and different active substances in the respective adjacent tablet layers can not influence one another.

In a preferred embodiment of the invention, in a device for producing multilayer tablets, the at least one bonding agent has a formulation that is liquid or solid at ambient temperature. Connecting agents may be used as so-called dry binders - examples being microcrystalline cellulose or starch - or as moisture binders or adhesives. Examples of possible representatives of moisture binders or adhesives known from the prior art are starch pastes, cellulose ethers, collidone and gelatin.

• Fischgelatine, 40%
• Polyvinylpyrrolidon (PVP), 20%
• Natrium-Carboxymethylcellulose (Molekulargewicht 90000, Low Molecular (LM)), 10%
• Natrium-Carboxymethylcellulose (Molekulargewicht 250000, High Molecular (HM), 5%
• Cellulose (Hydroxypropylmethylcellulose HPMC), 10%

Furthermore, in the context of the invention, the use of one or more of the following components or constituents in a connecting agent has proven to be advantageous:

• Fish gelatin, 40%
• Polyvinylpyrrolidone (PVP), 20%
• Sodium carboxymethyl cellulose (molecular weight 90000, Low Molecular (LM)), 10%
• Sodium Carboxymethylcellulose (molecular weight 250,000, High Molecular (HM), 5%
• Cellulose (hydroxypropylmethylcellulose HPMC), 10%

In a further embodiment variant of the invention, in a device for producing multilayer tablets, the application station comprises a tempering device for setting a temperature of the connection means. This is particularly advantageous in a bonding agent which, for example, has a viscous, highly viscous formulation at ambient temperature and which, in the heated state at low viscosity, can be applied much more simply and uniformly to a solid starting material or intermediate.

In one development of the invention, the bonding agent contains at least one active substance, preferably a pharmaceutical active substance. Furthermore, it is conceivable within the scope of the invention to also incorporate one or more active substances into a connecting means, which are applied together with the connecting means.

In a device according to the invention, it is particularly expedient to provide at least one cleaning station. By means of a cleaning station a cyclic cleaning of the entire conveyor unit or at least of individual conveyor containers is particularly easy. Regular cleaning of the wetted parts of the device is essential in particular when connecting means are used in order to ensure a consistent quality of the products and to avoid cross-contamination by deposits of connecting agents and / or intermediates in the conveying containers. If necessary, the at least one cleaning station may comprise a separate drying station to ensure that the cleaned device parts are also dried again before being used again in a subsequent production cycle. Likewise, it is provided in the context of the invention that one or more cleaning stations and one or more drying stations are each arranged at suitable locations in the course of the processing stations. Furthermore, it is possible in a device according to the invention to arrange at least one cleaning station and / or at least one drying station next to the conveyor unit or - depending on the embodiment of the device according to the invention - next to a rotary indexing table or next to a clock belt. Thus, processing stations that serve for cleaning of conveyor containers or the conveyor unit, also be positioned laterally next to, above or below the conveyor unit.

The modular arrangement of the processing stations further allows regular complete cleaning of individual or, if necessary, all in use processing stations of the device or a complete system for the production of multilayer tablets.

Preferably, the individual processing stations are designed such that they can be cleaned and / or sterilized in an autoclave.

In a multilayer tablet which is produced with a device according to the invention, at least one bonding agent is applied to a solid starting material and / or a geometrically limited intermediate product. Be beneficial in the Production of multilayer tablets with the device according to the invention one or more connecting means used in order to use the advantages of the use of connecting means described above can.

• Zuführen eines ersten festen Ausgangsstoffs und/oder eines ersten geometrisch begrenzten Zwischenprodukts an eine erste Beladestation;
• Übergeben des ersten festen Ausgangsstoffs und/oder des ersten geometrisch begrenzten Zwischenprodukts von der ersten Beladestation an eine Fördereinheit;
• Gegebenenfalls Überwachen der Zufuhr und/oder der Übergabe des ersten Ausgangsstoffs und/oder des ersten geometrisch begrenzten Zwischenprodukts an die erste Beladestation und/oder an die Fördereinheit;
• Transport des ersten Ausgangsstoffs und/oder des ersten geometrisch begrenzten Zwischenprodukts an eine erste Auftragestation;
• Aufbringen zumindest eines Verbindungsmittels auf dem ersten Ausgangsstoff und/oder dem ersten geometrisch begrenzten Zwischenprodukt in der ersten Auftragestation;
• Gegebenenfalls Durchlaufen einer oder mehrerer Zwischenstationen zum Kühlen, Erwärmen, Pressen, Trocknen, Bestrahlen und/oder Härten;
• Zuführen eines zweiten festen Ausgangsstoffs und/oder eines zweiten geometrisch begrenzten Zwischenprodukts an eine zweite Beladestation;
• Übergeben des zweiten festen Ausgangsstoffs und/oder des zweiten geometrisch begrenzten Zwischenprodukts von der zweiten Beladestation an die Fördereinheit bzw. an einen mit dem ersten Ausgangsstoff und/oder dem ersten geometrisch begrenzten Zwischenprodukt beladenen Förderbehälter;
• Gegebenenfalls Überwachen der Zufuhr und/oder Übergabe des zweiten Ausgangsstoffs und/oder des zweiten geometrisch begrenzten Zwischenprodukts an die zweite Beladestation und/oder die Fördereinheit;
• Transport des ersten Ausgangsstoffs und/oder des ersten geometrisch begrenzten Zwischenprodukts an eine Verbundstation;
• Verbinden des zweiten Ausgangsstoffs und/oder des zweiten geometrisch begrenzten Zwischenprodukts mit dem ersten Ausgangsstoff und/oder dem ersten geometrisch begrenzten Zwischenprodukt in der Verbundstation erforderlichenfalls durch Zugabe eines weiteren Verbindungsmittels;
• Gegebenenfalls weiteres Behandeln der verbundenen Ausgangsstoffe und/oder der verbundenen Zwischenprodukte in der Verbundstation oder in einer oder mehreren Zwischenstationen durch Kühlen, Erwärmen, Pressen, Trocknen, Bestrahlen und/oder Härten zu einem mehrschichtigen Tablettenkörper;
• Gegebenenfalls neuerliches Durchführen oder Wiederholen eines oder mehrerer vorgenannter Verfahrensschritte zur Verbindung eines oder mehrerer weiterer Ausgangsstoffe und/oder eines oder mehrerer weiterer geometrisch begrenzter Zwischenprodukte mit dem mehrschichtigen Tablettenkörper;
• Gegebenenfalls Beschichten, Färben, Trocknen, Glätten, Polieren und/oder Härten des mehrschichtigen Tablettenkörpers in einer Beschichtungsstation zu einer Mehrschichttablette;
• anschließender Transport der Mehrschichttabletten zu einer Entladestation;
• Entnehmen der Mehrschichttabletten aus der Fördereinheit;
• Gegebenenfalls Verpacken der Mehrschichttabletten in der Entladestation oder in einer Verpackungsstation;
• Optional Durchlaufen einer Reinigungsstation zur Reinigung zumindest eines Abschnitts der Fördereinheit;
• Optional Durchlaufen einer Trocknungsstation zum Trocknen zumindest eines Abschnitts der Fördereinheit.

A method for producing multilayer tablets, in which a device according to the invention is used, can be indicated by the following production steps:

• Feeding a first solid starting material and / or a first geometrically limited intermediate product to a first loading station;
• Transferring the first solid starting material and / or the first geometrically limited intermediate product from the first loading station to a conveying unit;
• Optionally monitoring the supply and / or the transfer of the first starting material and / or the first geometrically limited intermediate product to the first loading station and / or to the conveyor unit;
• Transporting the first starting material and / or the first geometrically limited intermediate product to a first application station;
• Applying at least one bonding agent on the first starting material and / or the first geometrically limited intermediate product in the first application station;
• Optionally passing through one or more intermediate stations for cooling, heating, pressing, drying, blasting and / or curing;
• Feeding a second solid starting material and / or a second geometrically limited intermediate product to a second loading station;
• Transferring the second solid starting material and / or the second geometrically limited intermediate product from the second loading station to the conveyor unit or to a delivery container loaded with the first starting material and / or the first geometrically limited intermediate product;
• Optionally monitoring the supply and / or transfer of the second starting material and / or the second geometrically limited intermediate product to the second loading station and / or the conveyor unit;
• Transporting the first starting material and / or the first geometrically limited intermediate product to a composite station;
• Connecting the second starting material and / or the second geometrically limited intermediate product with the first starting material and / or the first geometrically limited intermediate product in the connecting station, if necessary by adding a further connecting agent;
• Optionally further treating the combined starting materials and / or the associated intermediates in the composite station or in one or more intermediate stations by cooling, heating, pressing, drying, irradiating and / or curing to a multilayer tablet body;
• Optionally, repeating or repeating one or more of the aforementioned process steps for the connection of one or more further starting materials and / or one or more further geometrically limited intermediates with the multilayer tablet body;
• Optionally, coating, dyeing, drying, smoothing, polishing and / or curing the multilayer tablet body in a coating station to form a multilayer tablet;
• subsequent transport of the multilayer tablets to an unloading station;
• Removing the multilayer tablets from the conveyor unit;
• Optionally, packaging the multi-layer tablets in the unloading station or in a packaging station;
• Optionally passing through a cleaning station for cleaning at least a portion of the conveyor unit;
• Optionally, passing through a drying station for drying at least a portion of the conveyor unit.

In the context of the invention, it is provided that only a sequence of individual sub-steps of said manufacturing process can be run through. It is likewise conceivable to repeatedly pass through said production process in all sub-steps or in a selection of several sub-steps in order to obtain a two-layered or two-layered tablet body with the same device, for example in a first process run, in order to subsequently separate this tablet body into a further, second ( partially) process to form a four-layer or four-layer multilayer tablet. Furthermore, if necessary, a sub-step or several sub-steps may also be added to the said production process. Thus, it may be advantageous to carry out intermediate working steps, such as, for example, pre-curing of the applied bonding agent or cleaning of abrasion in the context of the method according to the invention.

• Fig. 1 eine erste Ausführung einer erfindungsgemäßen Vorrichtung zur Herstellung von Mehrschichttabletten in einer Draufsicht;
• Fig. 2 eine zweite Ausführung einer erfindungsgemäßen Vorrichtung zur Herstellung von Mehrschichttabletten in einer Draufsicht;
• Fig. 3 in einer isometrischen Ansicht von vorne eine erste Ausführung einer zylindrischen Mehrschichttablette, welche mit einer erfindungsgemäßen Vorrichtung bzw. mittels eines erfindungsgemäßen Verfahrens hergestellt wurde;
• Fig. 4 in einer isometrischen Ansicht von vorne eine zweite Ausführung einer bikonvexen Mehrschichttablette, welche mit einer erfindungsgemäßen Vorrichtung bzw. mittels eines erfindungsgemäßen Verfahrens hergestellt wurde.

Further details, features and advantages of the invention will become apparent from the following explanation of exemplary embodiments schematically illustrated in the drawings. In the drawings show:

• Fig. 1 a first embodiment of a device according to the invention for the production of multilayer tablets in a plan view;
• Fig. 2 a second embodiment of a device according to the invention for the production of multilayer tablets in a plan view;
• Fig. 3 in an isometric view from the front a first embodiment of a cylindrical multilayer tablet, which was produced with a device according to the invention or by means of a method according to the invention;
• Fig. 4 in an isometric view from the front, a second embodiment of a biconvex multilayer tablet, which was produced with a device according to the invention or by means of a method according to the invention.

In Fig. 1 a device 10 according to the invention with a curved machining path 20 is illustrated in a plan view. The device 10 has a delivery unit 50 with a plurality of delivery containers 51 and is embodied here by way of example as a rotary transfer table 52. The delivery containers 51 are moved in a transport direction 55, which is here identified by an arrow 55, along the substantially circular processing path 20. A plurality of processing stations 100 are arranged serially along the processing path 20, and a sequence of a plurality of successive process steps for the production of multilayer tablets can thus be processed in succession at individual, serially arranged processing stations 100. Advantageously, the number and / or the sequence of processing stations 100 are modularly variable.

If necessary, at individual processing stations 100 monitoring devices 57, such as devices for automatic visual inspection, arranged. Monitoring devices 57 may also be provided for monitoring quality parameters of current production, in particular for monitoring flow, mass or weight, density, temperature and / or composition in the context of device 10 according to the invention. For this purpose, if necessary, external monitoring devices, measuring devices, analyzers, sensors, etc. may be used and coupled to the corresponding processing stations 100 or integrated into them.

Starting materials are fed either as powdered starting materials or as granules 210, or as geometrically limited intermediates 220, for example as already pressed powder or powder mixtures in the direction of arrow 70, wherein an arrow 70 symbolizes a feed direction, a loading station 110. Furthermore, the Starting materials in the direction of arrow 75, which indicates a transfer direction 75 from the loading station 110 to the conveyor unit 50, are transferred to the conveyor unit 50 or to one or more delivery containers 51 of this conveyor unit 50.

The conveyor containers 51 are conveyed further by the conveyor unit 50 in the transport direction 55 and reach the next processing station 100, which serves as an applicator station 120 here. In the application station 120, a connection means 230 is applied to the solid starting material 210 or to the powder already pressed, for example, already to a geometrically limited intermediate product 220. An application or application of the connecting means 230 is symbolized as arrow 80. As a method for applying or applying 80 of the connecting means 230, for example, transfer methods can be used. Likewise, depending on the application, the connecting means 230 can be applied by spraying, dropping or by means of a screen printing process. The applicator station 120 is here in Fig. 1 equipped with a tempering 125, which serves tempering 125 for adjusting the temperature of the connecting means 230. This is particularly advantageous in a connection means 230 which, for example, has a highly viscous, viscous formulation at ambient temperature and which, in the heated state at low viscosity, can be applied much more simply and uniformly to the solid starting material. Together with the connecting means 230, which is sprayed here in the heated state or low viscosity on the solid starting material 210 located in the delivery container 51, an active substance 240 is additionally sprayed onto the starting material 210, which is contained in the connecting means 230 or admixed thereto has been.

In a further sequence, the transport containers 51 are further conveyed in the transport direction 55 and then pass through an intermediate station 130, in which here, for example, the applied connecting means 230 dried by blowing dried air and thus pre-cured. In the context of the invention, it is further conceivable that several intermediate stations 130, 131, 132, 133, etc. are passed through in series, which serve, for example, for cooling, heating, pressing, drying, irradiating and / or curing the media located in the conveyor containers 51 , These further intermediate stations are in Fig. 1 not explicitly shown.

In a subsequent processing station 100, which serves here as a further or second loading station 111, the transfer 75 of a second solid starting material 211 or a second already pressed to a geometrically limited intermediate product 220 takes place Powder or granules to the conveyor unit 50 and to the respective delivery container 51. The supply of the second solid starting material 211 and the second already to a geometrically limited intermediate 220 shaped powder or granules is symbolized by an arrow 70. It is likewise conceivable to supply a further active ingredient 241 to the device 10 at this point indicated by the arrow 70. Depending on the application or depending on the formulation, the further active compound 241 can optionally be added as an additive to the second solid starting material 211 or the second powder or granules already pressed to form a geometrically limited intermediate product 220. Likewise, the active ingredient 241 may already be present as a component in the starting material 211 or in the intermediate 220.

Further conveyed in the transport direction 55, the delivery container 51 then passes to a composite station 140. In the composite station 140, the second starting material 211 and / or the second geometrically limited intermediate 221 with the first starting material 210 and / or the first geometrically limited intermediate product 220 are added if necessary another connecting means 231 connected to each other.

Optionally, the interconnected starting materials 210, 211 and / or interconnected intermediates 220, 221 in the composite station 140 and / or in one or more other intermediate stations 131, 132, 133, etc. by cooling, heating, pressing, drying, irradiation and or hardening further treated and thus formulated into a multilayer tablet body 250.

In a subsequent coating station 150, the tablet bodies 250 may, if necessary, be further coated, dyed, dried, smoothed, polished and / or cured, thus obtaining a finished multilayer tablet 200.

Subsequently, the transport 55 of the multilayer tablets 200 takes place to an unloading station 160, where the multilayer tablets 200 are removed from the conveyor unit 50. Optionally, the multilayer tablets 200 are packaged in the unloading station 160 or in a subsequent packaging station 170.

Thereafter, the empty conveyor container 51 undergo an optional cleaning in a separate cleaning station 180 and - optionally also - a drying step in a drying station 190 before the corresponding of Verbindungsmittelresten or of adhering solid cleaned conveying container 51 are available for a new production cycle.

If necessary, one or more of the aforementioned method steps can also be repeated several times within a production cycle, or the corresponding processing stations 100 can be run through multiple times for this purpose. In Fig. 1 For this purpose, the position numbers of the respective processing stations are listed in ascending order in brackets, with the corresponding position numbers correspondingly increasing in the case of multiple, repeated passes.

For example, it is conceivable for the production of a so-called multi-layer tablet with three layers of solid starting materials, the conveyor container 51 on the rotary table 52 in the transport direction 55 more than a complete revolution to move and thus at least individual processing stations 100 to pass through several times. For example, in the apparatus 10 according to the invention, in a first pass, as described above, in the first loading station 110, a pulverulent first starting material 210 together with a first active substance 240 is loaded into a delivery container 51. This first starting material 210 together with the first active substance 240 is then sprayed in a dispensing station 120 with a first connecting means 230, for example, and then passes into a first intermediate station 130 in which the substances located in the corresponding conveyor 51 are pressed and cooled, wherein a first geometrically limited intermediate 220 - a single-layer tablet compact comprising the solid starting material 210, the active agent 240 and the connecting means 230 - is obtained.

Subsequently, the intermediate product 220 passes in the corresponding conveying container 51 to a second loading station 110, in which, for example, an already geometrically limited intermediate product 221, which contains a compacted granulate of a solid starting material 221 and a further active ingredient 241, is added to the intermediate product 220.

In the subsequent bonding station 140, the two intermediates 220 and 221 are joined together by adding a bonding agent 231, which also contains an active substance 140, for example. Subsequently, the rotary indexing table 52 is conveyed further in the transport direction 55 until the relevant conveyor container 51 again reaches the position of the original first loading station 110, which is now passed through as a loading station 112 a second time and in which another solid starting material 212 or another geometrically limited intermediate product 222 loaded become. In the applicator station 120, which is now also passed through a second time as the applicator station 121, a further connecting means 232 is applied to the meanwhile three-layered tablet body 251. Following this, the relevant delivery container 51 with the tablet body 251 therein optionally passes through further intermediate stations 132, 133, in which the tablet body 251 is pressed and hardened by means of UV light irradiation, for example, before the tablet body 251 is coated in the coating station 150, whereby a finished Multi-layer tablet 201 is obtained. Finally, the multilayer tablet 201 is transferred in the direction of arrow 85 from the conveyor unit 50 to the unloading station 160 and passes from the unloading station 160 on to the packaging station 170, in which the multilayer tablets 201 are packed in corresponding pack sizes.

As mentioned above by way of example, different sequences of processing steps for the production of multilayer tablets can be carried out particularly flexibly with the device 10 according to the invention. The processing stations 100 can be modularly varied in their arrangement and sequence along the processing path 20. Particularly when various connecting means are used, the cleaning station 180 and the drying station 190 are particularly advantageous for cleaning the rotary transfer table 52 or for cleaning the delivery containers 51.

Optional processing stations 100, for example one or more intermediate stations 130 (or 131, 132, 133, etc.), the packaging station 170 or the cleaning station 180 and drying station 190 are in Fig. 1 each drawn in dashed lines.

Instead of producing multilayer tablets containing powdery starting materials with active pharmaceutical ingredients, the device 10 can also be used, for example, for the preparation of soluble effervescent tablets, of nutritional supplements or of dishwasher tablets, dentures, or for comparable applications.

Fig. 2 shows a second embodiment of a device 11 according to the invention for the production of multilayer tablets in a plan view. In this device 11, the individual processing stations 100 are arranged serially along a substantially linear processing path 21.

The device 11 has a delivery unit 60 with a plurality of delivery containers 61 and is embodied here by way of example as a timing belt 62. The delivery containers 61 are moved in a transport direction 65, which is here identified by an arrow 65, along the substantially linear processing path 21. A plurality of processing stations 100 are arranged serially along the processing path 21, and a sequence of a plurality of successive process steps for the production of multilayer tablets can thus be processed in succession at individual, serially arranged processing stations 100. Advantageously, the number and / or the sequence of processing stations 100 are modularly variable. As in Fig. 1 shown schematically, the processing stations 100 are, for example, laterally next to the timing belt 62, which is why the starting materials 210 (or 211, 212, etc.) and / or the intermediates 220 (or 221, 222, etc.) respectively the respective processing stations 100th must be supplied. The assignment of the individual processing stations 100 to the respective position of the conveying container 61 on the timing belt 62 is here in Fig. 2 indicated by dash-dotted lines.

It is likewise conceivable to arrange the processing stations 100 next to or above the timing belt 62 in the apparatus 11 in such a way that the conveying containers 61 on the timing belt 62 are moved directly through the processing stations 100 during operation.

• eine erste Beladestation 110 zum Beladen eines ersten festen Ausgangsstoffs 210 bzw. eines ersten geometrisch begrenzten Zwischenprodukts 220 gemeinsam mit einem ersten Wirkstoff 240 in Übergaberichtung 75 an einen Förderbehälter 61; anschließend
• eine Auftragestation 120 zum Auftragen 80 eines ersten Verbindungsmittels 230; danach
• eine optionale Zwischenstation 130 (strichliert gezeichnet) zum Voraushärten des Verbindungsmittels 230 beispielsweise unter Einblasen von trockener Luft; weiters
• eine zweite Beladestation 111 zum Beladen eines weiteren festen Ausgangsstoffs 211 bzw. eines weiteren geometrisch begrenzten Zwischenprodukts 221 gemeinsam mit einem weiteren Wirkstoff 241 in Übergaberichtung 75 an den entsprechenden Förderbehälter 61;
• eine Verbundstation 140 zum Pressen und Aushärten der Zwischenprodukte 220, 221 zu einem mehrschichtigen Tablettenkörper 251; anschließend
• eine Beschichtungsstation 150 zum Beschichten und gegebenenfalls Färben des mehrschichtigen Tablettenkörpers 251, wobei eine fertige Mehrschichttablette 201 erhalten wird; abschließend
• eine Entladestation 160, in welcher die Mehrschichttablette 201 der Fördereinheit 60 bzw. dem entsprechenden Förderbehälter 61 entnommen wird bzw. an die Entladestation 160 übergeben 85 wird; und
• eine optionale Verpackungsstation 170 (strichliert gezeichnet) zur Verpackung der Mehrschichttabletten 201 in entsprechenden Packungsgrößen;
• zur Reinigung der leeren Förderbehälter 61 zwischen den einzelnen Herstellzyklen weiters eine optionale Reinigungsstation 180 kombiniert mit einer optionalen Trocknungsstation 190 (strichliert gezeichnet).

The here in Fig. 2 illustrated sequence of processing stations 100 is for example:

• a first loading station 110 for loading a first solid starting material 210 or a first geometrically limited intermediate product 220 together with a first active substance 240 in the transfer direction 75 to a delivery container 61; subsequently
• an application station 120 for applying 80 a first connection means 230; after that
• an optional intermediate station 130 (drawn in dashed lines) for pre-curing the connecting means 230, for example by blowing in dry air; further
• a second loading station 111 for loading a further solid starting material 211 or another geometrically limited intermediate product 221 together with another active substance 241 in the transfer direction 75 to the corresponding delivery container 61;
• a bonding station 140 for pressing and curing the intermediates 220, 221 into a multi-layered tablet body 251; subsequently
• a coating station 150 for coating and optionally coloring the multilayer tablet body 251 to obtain a finished multilayer tablet 201; finally
• an unloading station 160, in which the multilayer tablet 201 of the conveyor unit 60 or the corresponding conveyor container 61 is removed or transferred to the unloading station 160; and
• an optional packaging station 170 (shown in phantom) for packaging the multi-layer tablets 201 in appropriate package sizes;
• For cleaning the empty conveyor container 61 between the individual production cycles further an optional cleaning station 180 combined with an optional drying station 190 (dashed line drawn).

If necessary, also at individual processing stations 100 monitoring devices 57, for example, devices for automatic visual inspection, arranged. Further processing stations 100 can also be supplemented in a particularly flexible modular manner here with the device 11 with a linear processing path 21. Likewise, the sequence of processing stations 100 can be easily changed and varied in order to be able to fulfill with the device 11 the respective individual requirements for the production of different multilayer tablets.

Fig. 3 FIG. 2 illustrates in an isometric view from the front a first embodiment of a multilayer tablet 200, which was produced with a device according to the invention or by means of a method according to the invention. This multilayer tablet 200 consists of three layers of tablet pellets or powdery starting materials 210, 211, 212 connected to intermediates 220, 221, 222. In addition to the pulverulent, solid starting material 210, the intermediate product 220 further comprises a pharmaceutically active substance 240. Likewise, the intermediate product 221 comprises besides the powdery, solid starting material 211, a further active pharmaceutical ingredient 241. The intermediate product 222 further includes in addition to the powdery, solid starting material 212, a third pharmaceutical agent 242. The geometrically limited intermediates 220, 221 and 222 each have here a substantially cylindrical shape , Between the tablet pellets or between the intermediates 220, 221, 222 are each thin intermediate layers of a bonding agent 230. The multilayer tablet 200 shown here was pressed after application of bonding agent 230, dried and cured by UV irradiation.

Fig. 4 relates in an isometric view from the front a second embodiment of a multilayer tablet 201, which was also produced with a device according to the invention or by means of a method according to the invention. This multilayer tablet 201 likewise consists of three layers of tablet compacts or powdery starting materials 210, 211 and 213 connected to intermediates 220, 221, 223. The intermediate product 220 comprises, in addition to the pulverulent, solid The starting material 210 further comprises a first active pharmaceutical ingredient 240. Likewise, the intermediate product 221 arranged in the middle of the multi-layer tablet 201 comprises, in addition to the powdery, solid starting material 211, a further pharmaceutical active ingredient 242. The intermediate product 223 further contains no additional active pharmaceutical ingredient apart from the powdered solid starting material 213 , The multilayer tablet 201 here has a substantially biconvex shape with a round cross section and is arched on its upper side and on its underside.

Between the intermediate products 220, 221 there is a thin intermediate layer of a first connecting means 230. Between the intermediate products 221, 223 there is a thin intermediate layer of a second connecting means 232, which itself contains an active substance 242. The multilayer tablet 201 shown here was pressed after the application of bonding agent 230 or 232, dried and cured by UV irradiation. Furthermore, a possible coating or printing and / or dyeing of the multilayer tablet 201 are not explicitly shown here.

In the context of the invention, geometrically limited intermediates 220, 221, 222, 223 with the same or different shapes or contours can also be combined with one another in order to form further multilayer tablet structures. The embodiments of multilayer tablets according to the invention may comprise all types of tablets in any desired shape or contour. Thus, multilayer tablets made by the method of the invention may have, for example, a circular, oval or polygonal top view and / or may have rounded or sharp edges.

Likewise, multilayer tablets made by the process of the present invention may include interfaces between adjacent tablet layers which are performed in complementary mating engagement structures to achieve a positive engagement. For example, individual or all layers or geometrically limited intermediates of a multilayer tablet may be positively connected to each other by one or more teeth in step shape, serrated shape, dovetail shape and / or waveform. Thus, advantageously, a multilayer tablet is produced in which an undesired separation ("lapping") of adjoining layers is reliably prevented.

List of position signs:

10

Device (or 11)

20

curved machining path

21

linear machining path

50

Feed unit (or 60)

51

Delivery container (or 61)

55

Transport direction (arrow) (or 65)

52

Rotary table

57

Monitoring device (for visual inspection)

62

timing belt

70

Supply to the loading station (arrow)

75

Transfer from the loading station to the conveyor unit (arrow)

80

Applying or applying a bonding agent (arrow)

85

Transfer from the delivery unit to the unloading station (arrow)

100

processing station

110

Loading station (or 111, 112, 113, ...)

120

Order station (or 121, 122, 123, ...)

125

tempering

130

Intermediate station (or 131, 132, 133, ...)

140

Connection station (or 141, 142, 143, ...)

150

Coating station (or 151, 152, 153, ...)

160

Unloading station (or 161, 162, 163, ...)

170

packing station

180

cleaning station

190

drying station

200

Multilayer tablet (or 201)

210

solid starting material (or 211, 212, 213)

220

geometrically limited intermediate product (or 221, 222, 223)

230

Connecting means (or 231, 232, 233)

240

Active substance (or 241, 242, 243)

250

multilayer tablet body (or 251)

Claims (15)

Device (10, 11) for producing multilayer tablets (200, 201) from solid starting materials (210, 211, 212, 213), in particular from powders, granules and / or from geometrically limited intermediates (220, 221, 222, 223), comprising a plurality of processing stations (100) and a conveyor unit (50, 60) with a plurality of conveyor containers (51, 61), characterized in that the individual processing stations (100) are modularly variable in their arrangement. Device (11) according to claim 1, characterized in that the processing stations (100) are arranged serially along a substantially linear processing path (21). Apparatus (10) according to claim 1, characterized in that the processing stations (100) are arranged serially along a curved processing path (20), preferably along a closed curved processing path. Device (10, 11) according to one of claims 1 to 3, characterized in that the processing stations (100) are arranged in one plane, preferably in a substantially horizontal plane. Device (10, 11) according to one of claims 1 to 4, characterized in that for the production of multilayer tablets (200, 201) at least one of the processing stations (100) is repeatedly passable. Device (10, 11) according to one of claims 1 to 5, characterized in that in a processing station (100) at the same time several fixed
Starting materials (210, 211, 212, 213) and / or a plurality of geometrically limited intermediates (220, 221, 222, 223) are machinable. Device (10, 11) according to one of claims 1 to 6, characterized in that of the conveyor unit (50, 60) in a manufacturing cycle, the solid starting materials (210, 211, 212, 213) and / or the geometrically limited intermediates (220 , 221, 222, 223) each from a preceding one Processing station (100) to a in the transport direction (55, 65) subsequent processing station (100) can be transferred. Device (10, 11) according to claim 7, characterized in that the solid starting materials (210, 211, 212, 213) and / or the geometrically limited intermediates (220, 221, 222, 223) at least between two adjacent processing stations (100). remain within their respective delivery container (51, 61). Device (10, 11) according to one of claims 1 to 8, characterized in that at least one applicator station (120, 121, 122, 123) for the application of at least one bonding agent (230, 231, 232, 233) on a solid starting material ( 210, 221, 212, 213) and / or a geometrically limited intermediate product (220, 221, 222, 223) is provided. Device (10, 11) according to claim 9, characterized in that the at least one connecting means (230, 231, 232, 233) has a liquid or solid formulation at ambient temperature. Device (10, 11) according to claim 9 or 10, characterized in that the applicator station (120, 121, 122, 123) comprises a tempering device (125) for setting a temperature of the connecting means (230, 231, 232, 233). Device (10, 11) according to one of Claims 9 to 11, characterized in that the connecting means (230, 231, 232, 233) contains at least one active substance (240, 241, 242, 243), preferably a pharmaceutical active substance. Device (10, 11) according to one of claims 1 to 12, characterized in that at least one cleaning station (180) is provided. Multi-layer tablet (200, 201) produced by a device (10, 11) according to one of claims 1 to 13, characterized by at least one connecting means (230, 231, 232, 233) mounted on a solid starting material (210, 211, 212 , 213) and / or a geometrically limited intermediate product (220, 221, 222, 223) is applied. Method for producing multilayer tablets (200, 201) with a device (10, 11) according to one of Claims 1 to 13, characterized by the following production steps: - feeding (70) a first solid starting material (210) and / or a first geometrically limited intermediate product (220) to a first loading station (110); - transferring (75) the first solid starting material (210) and / or the first geometrically limited intermediate product (220) from the first loading station (110) to a conveying unit (50, 60); Optionally monitoring (57) the supply (70) and / or the transfer (75) of the first starting material (210) and / or the first geometrically limited intermediate product (220) to the first loading station (110) and / or to the conveyor unit ( 50, 60); - Transport (55, 65) of the first starting material (210) and / or the first geometrically limited intermediate product (220) to a first applicator station (120); - applying (80) at least one connecting means (230) on the first starting material (210) and / or the first geometrically limited intermediate product (220) in the first application station (120); Optionally passing through one or more intermediate stations (130, 131, 132, 133) for cooling, heating, pressing, drying, irradiation and / or curing; - feeding (70) a second solid starting material (211) and / or a second geometrically limited intermediate product (221) to a second loading station (111); - Passing (75) of the second solid starting material (211) and / or the second geometrically limited intermediate product (221) from the second loading station (111) to the conveyor unit (50, 60) or one with the first starting material (210) and / or the first geometrically limited intermediate product (220) loaded conveyor container (51, 61); Optionally monitoring (57) the supply (70) and / or transfer (75) of the second starting material (211) and / or the second geometrically limited intermediate product (221) to the second loading station (111) and / or the conveying unit (50, 60); - Transport (55, 65) of the first starting material (210) and / or the first geometrically limited intermediate product (220) to a composite station (140); - Connecting the second starting material (211) and / or the second geometrically limited intermediate product (221) with the first starting material (210) and / or the first geometrically limited intermediate product (220) in the Composite station (140) if necessary by adding a further connection means (231, 232); Optionally further treating the combined starting materials (210, 211) and / or the associated intermediates (220, 221) in the bonding station (140) or in one or more intermediate stations (130, 131, 132) by cooling, heating, pressing, drying Irradiating and / or curing to a multilayer tablet body (250, 251); Optionally renewing or repeating one or more of the aforementioned method steps for connecting one or more further starting materials (212, 213) and / or one or more further geometrically limited intermediates (222, 223) to the multilayer tablet body (250, 251); Optionally coating, dyeing, drying, smoothing, polishing and / or curing the multilayer tablet body (250, 251) in a coating station (150) into a multilayer tablet (200, 201); - subsequent transport (55, 65) of the multilayer tablets (200, 201) to an unloading station (160); - removing the multilayer tablets (200, 201) from the conveyor unit (50, 60); Optionally packaging the multilayer tablets (200, 201) in the unloading station (160) or in a packaging station (170); - optionally passing through a cleaning station (180) for cleaning at least a portion of the conveyor unit (50, 60); - Optional passing through a drying station (190) for drying at least a portion of the conveyor unit (50, 60).

Images