EP3515581B1 - Module de production et procédé pour la fabrication de formes médicamenteuses solides - Google Patents

Module de production et procédé pour la fabrication de formes médicamenteuses solides Download PDF

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Publication number
EP3515581B1
EP3515581B1 EP17751038.5A EP17751038A EP3515581B1 EP 3515581 B1 EP3515581 B1 EP 3515581B1 EP 17751038 A EP17751038 A EP 17751038A EP 3515581 B1 EP3515581 B1 EP 3515581B1
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EP
European Patent Office
Prior art keywords
sluice
collection
mixing device
production module
distinguished
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP17751038.5A
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German (de)
English (en)
Other versions
EP3515581A1 (fr
Inventor
Marc Michaelis
Syed Muhammad Mushahid Azher
Matthias BOERNER
Christian Karl Paasche
Christian Gebauer
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Huettlin GmbH
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Huettlin GmbH
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Publication of EP3515581A1 publication Critical patent/EP3515581A1/fr
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/60—Mixing solids with solids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/714—Feed mechanisms for feeding predetermined amounts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
    • B01F35/71805—Feed mechanisms characterised by the means for feeding the components to the mixer using valves, gates, orifices or openings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/75—Discharge mechanisms
    • B01F35/754—Discharge mechanisms characterised by the means for discharging the components from the mixer
    • B01F35/7547—Discharge mechanisms characterised by the means for discharging the components from the mixer using valves, gates, orifices or openings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/10—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of compressed tablets

Definitions

  • the present invention relates to a production module for producing solid dosage forms.
  • Solid dosage forms are understood to mean, in particular, tablets, pills or capsules.
  • a production module according to the preamble of claim 1 is in DE-C2-33 90 423 disclosed.
  • the production module according to the invention comprising several process units for producing solid dosage forms in individual lots allows pharmaceutical powders to be processed fully automatically into solid dosage forms, in particular tablets and capsules.
  • the automation ensures that process limits are automatically observed for all important or necessary process parameters in every process unit of the production module. This also allows an automatic detection of occurring technical problems with each individual process unit and a message to a user, in particular via an HMI, i.e. a human machine interface. Finally, the automation also enables automatic cleaning of the entire production module, or in particular also of individual process units, after a production process.
  • the lots are preferably passed on from an upstream to a downstream process unit without having to remove the product from the production module.
  • the manufacturing steps within the production module can preferably be coordinated with such lots, the mixing of the individual lots being largely prevented.
  • the recorded production data from each device and each unit are preferably linked to each relevant lot and stored so that the process path through the individual modules and units of this lot can be tracked.
  • the substance name, material number, batch number, date of manufacture, mass of the respective batch and dosing factor (purity factor of the excipients and the API), which are weighed into the powder sources (IBC), are ideally weighed in by the user or by scanning these data into the control device of the production module made available.
  • Scanning is to be understood in particular that said parameters are present in coded form on a storage container, so that when the storage container is connected to the supply device, manual or automatic detection of the coded parameters can be read out and fed to the control device.
  • This information is automatically linked to each lot made up of these batches.
  • the production module comprises a feeding device, a mixing device, a finishing device, a cleaning device and a control device.
  • the production module has a transport network for powder and / or manufactured granules, tablets and / or capsules, which is preferably assigned to the individual devices Lines and nodes is based.
  • the individual devices are connected to one another via this transport network.
  • the feed device is connected to the mixing device.
  • the mixing device is preferably connected to the finishing device.
  • the mixing device, the finishing device and the feed device represent, in particular, individual process units of the production module.
  • the supply unit preferably has a metering unit for each supplied starting material.
  • a defined amount of starting materials can be fed to the production module, in particular the mixing device.
  • the feed device is used to feed raw materials in order to define each solder.
  • the starting materials are preferably powdered pharmaceutical substances.
  • the mixing device is used to mix the defined lot of the supplied starting materials. In addition, processing, in particular granulating and / or drying, and coating of the supplied starting materials can preferably take place within the mixing device.
  • the finishing device is used to finish the mixed and / or granulated and / or coated starting materials into an end product. This includes in particular the shaping of the mixed and / or granulated and / or coated starting materials. In this way, the solid medicaments in particular can be shaped.
  • the production module also includes a control device.
  • the control device is designed for fully automatic control of the feed device, mixing device and finishing device as well as a cleaning device that is preferably present.
  • the control device is set up to transport a substrate in the form of a solder from the feed device to the mixing device and from the Mixing device to control the finishing device. In particular, no manual intervention is necessary. An entire production cycle starting with the supply of the required starting materials up to the dispensing of the finished solid medicament forms from the finishing device thus preferably runs automatically and without the intervention of a user.
  • the control device also enables the production data to be saved and linked to the individual lots.
  • the control device can preferably be used to link data from all available process sensors and quality sensors of the production module to the respective lots, which enables each lot to be tracked later or each lot to be tracked in real time.
  • a transfer of each lot from the supply device to the mixing device and from the mixing device to the finishing device can be carried out without backmixing through a collecting sluice. In particular, this prevents each solder from coming into contact with other substrates that are not intended for processing the solder. In particular, several lots can therefore be processed simultaneously in the production module, since separation of the individual lots is ensured at all times by the collecting sluices.
  • the production module of the invention is defined by the features of claim 1.
  • a method for the production of solid dosage forms is defined in claim 11.
  • the subclaims show preferred developments of the invention.
  • a first collecting sluice is arranged between the feed device and the mixing device.
  • the first collecting sluice serves to prevent fluid communication between the supply device and the mixing device. In this way, quality assurance is made possible.
  • the starting material can thus be transferred from the feed device into the first collecting sluice.
  • the starting material can then be fed to the mixing device from the first collecting sluice. There is therefore always a defined amount of starting materials within the first collecting sluice that are to be fed to the mixing device.
  • the first collecting sluice for highly precisely dosed pharmaceutical powdery substances advantageously has at least one agitator for mixing and / or equalizing and / or homogenizing the powdery substances, and ideally also at least one measuring nozzle for at least one quality sensor and at least one Quality sensor to control the purity of the dosed substances, mixing quality, particle size distribution and, if necessary, input moisture of the highly precisely dosed pharmaceutical powders under constant conditions.
  • the first collecting sluice preferably has at least one opening for entering the powdery substances and an outlet.
  • a second collecting sluice is arranged between the mixing device and the finishing device.
  • the second collecting sluice is used to prevent, in particular briefly, continuous fluid communication between the mixing device and the finishing device, and to hold material for the uninterrupted production process in the finishing device in the event of a delay in the process in the upstream modules. This in turn enables quality assurance.
  • a product produced by mixing and / or granulating and / or coating the starting materials can thus be transferred from the mixing device into the second collecting sluice.
  • the product can be transferred from the second collecting sluice to the finishing device, so that there is no direct fluid communication between the mixing device and the finishing device.
  • This second collecting sluice can ideally like the first collecting sluice with at least one agitator, at least one measuring connector for at least one quality sensor to control the mixed and / or granulated and / or dried and / or coated substances with regard to purity, mixing quality, particle size distribution and, if necessary, Humidity of the pharmaceutical substances equipped to be under constant conditions.
  • the second collecting sluice can mix the processed product from the mixing device with other substances.
  • the other substances can be added to the second collecting sluice, in particular via an additional dosing unit.
  • the other substances are, in particular, magnesium stearate or other additives referred to as the outer phase.
  • a switch is preferably installed between the second collecting sluice and the finishing device.
  • a solder can be discharged via the switch and, in particular, transferred into a waste container. This prevents a product that does not meet predefined quality criteria fulfilled, remains in the transport network of the production module. In this way, in particular, contamination of the transport network with products of inferior quality is prevented.
  • a third collecting sluice is preferably arranged between the finishing device and a module boundary of the production module.
  • the module limit is to be understood as a limit of the production module on the finished end product, that is, solid dosage forms that leave the production module.
  • a limit at which the starting materials are entered into the production module is preferably viewed as the module limit. Fluid communication between the surroundings of the production module and the finishing device is thus prevented by the third collecting sluice. This in turn enables quality assurance. In addition, contamination of the production module by external influences is prevented.
  • the third collecting sluice can ideally be a deduster or a simple container. Quality sensors are preferably attached to the third collecting sluice in order to enable quality controls under constant conditions.
  • the first collecting sluice and / or the second collecting sluice and / or the third collecting sluice and / or the fourth collecting sluice allow a monitoring of a product quality particularly advantageously.
  • at least one quality sensor is attached within the first collecting sluice and / or the second collecting sluice and / or in the third collecting sluice and / or in the fourth collecting sluice. With the quality sensor, the quality of the content of the respective collecting sluice can be detected. In this way it is possible for the control device to determine and monitor the quality of the contents of the collecting sluices.
  • At least one pharmaceutical active ingredient and at least one pharmaceutical excipient can preferably be supplied via the supply device.
  • a pharmaceutical active ingredient and a large number of different pharmaceutical excipients are particularly preferably supplied.
  • Both the pharmaceutical active ingredient and the pharmaceutical excipient are preferably a powder.
  • the finishing device preferably comprises a tablet press and / or a capsule filler.
  • the tablet press and / or the capsule filler can be used to manufacture solid pharmaceutical forms from the product produced by the mixing device by mixing the starting materials. In this way, different geometric shapes of the solid dosage forms can be produced.
  • the tablets produced are also preferably coated in an optional coating device.
  • the feed device comprises at least one metering unit for highly precise metering of the pharmaceutical powdery components.
  • the feed device preferably has a collecting container for receiving the highly precisely dosed pharmaceutical powdery substances.
  • this collecting container can alternatively be equipped with at least one agitator for mixing the powdery substances, and ideally additionally with at least one measuring connector for at least one quality sensor and at least one quality sensor for checking the purity of the dosed substances, mixing quality, particle size distribution and, if necessary, input moisture of the highly precisely dosed pharmaceutical powders be equipped.
  • the collecting container has at least one opening for entering the powdery substances and an outlet.
  • the mixing device preferably comprises a fluidized bed system in which drying and / or granulation can take place, or a wet granulator.
  • the wet granulator preferably comprises an extruder and / or high-shear mixer.
  • a mixing process in the broadest sense takes place in the mixing device.
  • a mixing device is not to be understood as a screw feeder, since only substances are present here in the purest form. The mixing process can thus be regarded as synonymous with a drying process and / or a granulating process.
  • the tablet press and / or the capsule filler is preferably followed by a coating device.
  • the coating device is used in particular to coat the tablets produced or the capsules produced. It is also preferably provided that between the tablet press and / or the capsule filler and the coating device a fourth collecting sluice is arranged.
  • the fourth exit lock allows quality assurance to be enabled.
  • the fourth exit lock prevents direct fluid communication between the tablet press and / or the capsule filler and the coating device. Fluid communication between the finishing device and the environment is thus prevented by the fourth collecting sluice.
  • quality assurance is again made possible.
  • contamination of the finishing device by external factors is prevented.
  • a fourth collecting sluice can in particular also be present if the production module does not have a third collecting sluice.
  • the production module preferably comprises a cleaning device, which can be started and run partially or fully automatically by the user via a man-machine interface.
  • the feeding device, the mixing device and the finishing device can be cleaned together and / or separately from one another, so that partial manual cleaning by the user (WIP-Wipe In Place), but preferably no manual cleaning (CIP-Clean In Place) is necessary is.
  • Quality sensors are preferably attached to the individual process unit of the mixing device in order to release the transfer of good product, which means that predefined quality features are met, into the transport network, or to release a bad product, which means that predefined quality features are not met, if possible not in to allow the transport network to arrive and to discharge it directly to or from the units of the mixing device manually or automatically with a suction device into a waste container,
  • the invention also relates to a method for the production of solid dosage forms with a production module as described above. It is provided that starting materials to be used are dosed with high precision into the first collecting sluice by means of a dosing unit in the feed device. This is how each lot is defined. It is particularly advantageous that always during production the same amounts are used. It is particularly advantageous to always dose the same proportions of mass.
  • each lot is preferably processed separately in the feed device and subsequently separately in the mixing device and subsequently separately in the finishing device.
  • the respective solder is transported into a collecting sluice in order to be checked there by means of a quality sensor and for its suitability for further processing.
  • each solder is granulated and dried in the mixing device in only one process unit.
  • each solder is granulated in the mixing device in an extruder or in a high shear granulator and then dried in a processing unit of the mixing device. Since the mixing device advantageously has several process units, the mixing device can process several lots at the same time. The individual lots are preferably kept separate from one another so that mixing of the individual lots is impossible.
  • further substances can be fed into the second collecting sluice by at least one additional dosing unit.
  • the other substances can be mixed with the respective solder that is located in the second collecting sluice.
  • the other substances are, in particular, magnesium stearate or other additives referred to as the outer phase.
  • Each lot is preferably checked by quality sensors, the quality sensors being mounted in the individual process units of the mixing device. In this way, it can be decided whether a respective lot is released into the transport network or whether it is manually or automatically discharged into a waste container directly after or from the processing units of the mixing device. In this way, if predefined quality parameters are not achieved, each lot can be ejected via a switch into a waste container before the lot reaches the finishing device.
  • FIG. 1 shows schematically an illustration of a production module 1 for manufacturing solid dosage forms 22 according to an embodiment of the invention.
  • the production module 1 comprises a feeding device 2, a mixing device 3, a finishing device 4 and a control device 5 and a cleaning device (36).
  • the feed device 2, the mixing device 3 and the finishing device 4 preferably represent process units of the production module 1.
  • Starting materials 17, 18, 19, 20 can be fed to the production module 1 via a module boundary 8 via the feed device 2.
  • the starting materials 17, 18, 19, 20 can be transported to the mixing device 3 via the feed device 2. This is in Figure 2 shown.
  • Figure 2 shows schematically a partial area of the production module 1.
  • the starting materials 17, 18, 19, 20 are in particular a pharmaceutical active ingredient 17 and a first pharmaceutical excipient 18, a second pharmaceutical excipient 19 and a third pharmaceutical excipient 20.
  • the inlets for the starting materials 17, 18, 19, 20 are preferably releasably connected to source containers (not shown).
  • the starting materials are in particular pharmaceutical powders.
  • the feed unit 2 comprises a first metering unit 13, a second metering unit 14, a third metering unit 15 and a fourth metering unit 16.
  • the pharmaceutical active ingredient 17 that is supplied can be metered via the first metering unit 13.
  • the first pharmaceutical excipient 18 can be dosed via the second dosing unit 14, the second pharmaceutical excipient 19 via the third dosing unit 15 and the third pharmaceutical excipient 20 via the fourth dosing unit 16.
  • a composition of the starting materials 17, 18, 19, 20 can thus be set precisely.
  • a first collecting sluice 6 is provided between the feed device 2 and the mixing device 3. It is provided that the first dosing unit 13 optionally via a first check valve 23, the second dosing unit 14 optionally via a second check valve 24, the third dosing unit 15 optionally via a third check valve 25 and the fourth dosing unit 16 optionally via a fourth check valve 26 with the first collecting sluice 6 is connected. Furthermore, the collecting sluice 6 has a filter 35 to enable air to flow into and out of the collecting sluice 6.
  • the metering units 13, 14, 15, 16 can preferably run in a common collecting pipe and thus be connected to the collecting sluice 6.
  • the fifth shut-off valve 27 is preferably only opened when both the first optional blocking valve 23, the second optional blocking valve 24, the third optional Check valve 25 and the fourth optional check valve 26 are all closed.
  • the first collecting sluice 6 thus enables direct fluid communication between the metering units 13, 14, 15, 16 and thus the feed device 2 and the Mixing device 3 is prevented. In this way, quality assurance can be made possible.
  • a quality sensor not shown, is located in the first collecting sluice 6, via which the quality of the starting materials 17, 18, 19, 20 can be checked.
  • the quality sensor is advantageously connected to the control device 5, so that the control device 5 can carry out the quality control fully automatically.
  • at least one agitator element is located in the collecting sluice 6 for equalizing and homogenizing the metered bulk.
  • the at least one mixing device 3 is connected downstream of the first collecting sluice 6.
  • the mixing device 3 has a sixth shut-off valve 28 at its inlet.
  • a supply of the starting materials 17, 18, 19, 20 to the mixing device 3 can be regulated with the sixth shut-off valve 28.
  • Mixing devices 3 are understood to mean only collections of such process units in which a mixing process takes place in the broadest sense of different materials.
  • the mixing device 3 is a fluidized bed system, a wet granulator, preferably a high-shear mixer or extruder, or some other mixing apparatus.
  • screw feeders are not regarded as mixing device 3, since substances are present here in the purest form.
  • the mixing device 3 preferably has a large number of individual process units.
  • the process units are connected via a distribution system and / or a separate collection system. Via the distribution system and / or the collection system, defined product quantities can be transported between the process units and / or the feed device and / or the finishing device, ideally gravimetrically or pneumatically.
  • the mixing device 3 is followed by a finishing device 4. Parts of the finishing device 4 are also shown in FIGS Figures 3 and 4th shown. In particular, a final manufacturing process takes place in the finishing device 4 in order to manufacture solid medicament forms 22.
  • the mixing device 3 is followed by a seventh shut-off valve 29.
  • the seventh shut-off valve 29 is outputting mixed and preferably also granulated starting materials 17, 18, 19, 20 from the mixing device 3 can be controlled.
  • Downstream that is, downstream of the mixing device 3, there is a second collecting sluice 7.
  • the second collecting sluice 7 is preferably designed in a conceptually analogous manner to the first collecting sluice 6 with measuring nozzle and agitator.
  • the second collecting sluice also allows a separation of fluid communication between the mixing device 3 and the finishing device 4, as well as a uniform and / or homogenizing of the lot (new number) from the mixing device 3.
  • the second collecting sluice 7 can have at least one further opening for magnesium stearate and other substances designated as the outer phase. This at least one opening is ideally connected to at least one additional metering unit 21 for this purpose.
  • the second collecting sluice 7 optionally has an eighth shut-off valve 30 and ideally a ninth shut-off valve 31.
  • An inlet of pharmaceutical granules or powder from the mixing device 3 into the second collecting sluice 7 can be controlled via the eighth shut-off valve 30.
  • a discharge of fluid from the second collecting sluice 7 can be controlled via the ninth shut-off valve 31.
  • a quality control can again preferably be carried out within the second collecting sluice 7.
  • controllable means the possibility of forwarding the solder good product into the finishing device 4, or if necessary the solder good product into an IBC (Intermediate Bulk Container - not shown), or the solder bad product into a waste container (not shown).
  • the finishing device 4 comprises, as in FIG Figure 1 shown, preferably a tablet press or a capsule filler 11 and a downstream coating device 10.
  • the coating device 10 is in particular optional. So is in Figure 1 It is shown that finished solid medicament forms 22 can be removed from both the tablet press or the capsule filler 11 and from the coating device 10.
  • the completed solid dosage forms 22 are preferably dispensed over the module limit 8.
  • Figure 4 finally shows a third section from the production module 1. It can be seen that the finishing device 4 is followed by a third collecting sluice 9.
  • the solid medicament forms 22 produced can thus be dispensed via the third lock 9 to an environment, that is to say beyond the module boundary 8.
  • the third collecting sluice 9 optionally has a tenth blocking module 33 at the entrance and a twelfth blocking module 34 at the exit. This in turn ensures that no fluid communication whatsoever can take place between the finishing device 4 and an environment of the production module 1.
  • a final inspection of the solid medicament forms 22 produced preferably takes place within the third collecting sluice 9. Such a control is carried out in particular with regard to mass, height, diameter, hardness and preferably the content of the pharmaceutical active ingredient.
  • a coating device 10 it is also preferably provided that a fourth collecting sluice 12 is present between the tablet press or the capsule filler 11 and the coating device 10.
  • the fourth collecting lock 12 prevents fluid communication between the coating device 10 and the tablet press or the capsule filler 11. This in turn also provides the possibility of quality assurance.
  • shut-off valves 23, 24, 25, 26, 27, 28, 29, 30, 31, 2, 30, 33, 34, if present, can be controlled by the control device 5.
  • the feed device 2, the mixing device 3 and the finishing device 4, which means in particular the coating device 10 and the tablet press or the capsule filler 11, and the cleaning device 36 can be controlled by the control device 5.
  • a fully automatic process sequence within the module limit 8 is thus preferably ensured. This means that no user intervention is necessary in order to produce the finished solid medicament forms 22 on the basis of the starting materials 17, 18, 19, 20. In particular, this also avoids the need to manually establish connection processes between individual process units by a user, thereby avoiding possible leaks.
  • the production module 1 is not enclosed by a dwelling.
  • Housing is to be understood as a housing that includes all Process units, that is to say the supply device 2, the mixing device 3 and the finishing device 4, would include and separate them from the immediate vicinity (GMP production room / clean room). Rather, it is provided that each process unit has its own walls in order to close off the process rooms from the environment (GMP room / clean room). In particular, this enables full access to the individual process units in the event that maintenance or cleaning is necessary.
  • a production of solid dosage forms 22 by means of the production module 1 described above advantageously proceeds as follows:
  • the starting materials 17, 18, 19, 20, in particular in powder form are pneumatically, preferably gravimetrically, transported from source containers to the feed device 2.
  • the starting materials 17, 18, 19, 20 are introduced into the first collecting sluice 6 with high precision, automatically and coordinated with one another.
  • a solder is thus present within the first collecting sluice 6.
  • Quality examinations can be carried out here using quality sensors.
  • quality examinations include recording a moisture content, a composition and a particle size distribution of the starting materials 17, 18, 19, 20, and ideally their purity. This enables corrections to be made at this point.
  • the solder can also ideally be homogenized here.
  • the composition can ideally be checked, ensured and corrected here via the metering units 13, 14, 15, 16.
  • the solder from the first collecting sluice 6 is only passed on if the quality is confirmed to be good.
  • the first shut-off valve is 23, the second shut-off valve 24, the third shut-off valve is 25 and the fourth shut-off valve is closed, if present.
  • the fifth shut-off valve 27 is opened. In this way it is ensured that no fluid communication can take place between the feed device 2 and the mixing device 3 during the transport of the defined product quantity from the first collecting sluice 6.
  • the solder is preferably supplied to at least one first process unit and preferably at least via a distribution system of the mixing device 3 a second process unit, wherein the process units are preferably parts of a fluidized bed granulation system and are individual, independent granulation units. Fluidized bed granulation system thus has several, in particular similar, process rooms.
  • the supplied solder is processed according to a predefined method, in particular mixed and / or granulated. Downstream of the mixing device 3 is the second collecting sluice 7 in order to collect the, in particular mixed and / or granulated and / or dried, products processed by the mixing device 3.
  • good product is passed on from the mixing device 3 via the transport network to the following unit.
  • a message is output to the user on the HMI and the user can automatically or manually remove the bad product from the mixing device.
  • a quality control is advantageously carried out again in the second collecting sluice 7. In this way, faulty batches can be identified at an early stage and, if necessary, sorted out with the aid of the switch 32. Furthermore, it is possible with the at least one additional metering unit 21 to meter magnesium stearate or other substances referred to as outer phase into the processed product with high precision.
  • the contents of the second collecting sluice 7 can be transported to the finishing device 4. Again, it is optionally ensured that fluid communication between the mixing device 3 and the finishing device 4 is avoided.
  • the content of the second collecting sluice 7 is delivered to the tablet press or the capsule filler 11.
  • the transferred product is processed into tablets or capsules. If tablets are produced, they are advantageously transferred to the fourth collecting lock 12.
  • the tablets are transferred from the fourth collecting lock 12 to the coating device 10. Again, on the one hand, fluid communication between the tablet press or capsule filler 11 and the coating device 10 is avoided by the fourth collecting lock 12, on the other hand, the fourth collecting lock 12 allows quality control to be carried out.
  • the tablets are coated with a film by the coating device 10. Subsequently, the thus completed solid drug forms 22 are dispensed into a third collecting lock 9. If capsules are to be produced, the capsules and thus the completed solid drug forms 22 are preferably dispensed from the tablet press or the capsule filler 11 into the third receiving lock 9 third collection sluice 9, a fluid communication with the environment is again prevented, and a final quality test can also be carried out.
  • the process described above can be carried out fully automatically by the control device 5.
  • the control device 5 By the presence of quality sensors in the collecting sluices (6, 7, 9, 12) as well as in the feeding device (2), the mixing device (3) and the finishing device (4), the first collecting sluice 6, the second collecting sluice 7, the third collecting sluice 9, and the fourth collecting sluice 12, a transport and constant quality control between and in the individual units of the production module 1 is made possible. In particular, no manual intervention by a user is necessary.

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  • Medical Preparation Storing Or Oral Administration Devices (AREA)
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Claims (15)

  1. Module de production (1) pour fabriquer des formes pharmaceutiques solides (22) en lots (37, 38, 39, 40) individuels, comprenant
    • un dispositif d'amenée (2) pour amener des matières de départ pulvérulentes,
    • un dispositif de mélange (3), relié au dispositif d'amenée (2), pour traiter les matières de départ pulvérulentes amenées en un produit,
    • un dispositif de traitement final (4), relié au dispositif de mélange (3), pour finir un produit final à partir des matières de départ traitées, et
    • un dispositif de commande (5) pour commander automatiquement le dispositif d'amenée (2) et le dispositif de mélange (3) et le dispositif de traitement final (4),
    - dans lequel une transmission d'un lot (37, 38, 39, 40) du dispositif d'amenée (2) au dispositif de mélange (3) et du dispositif de mélange (3) au dispositif de traitement final (4) peut être effectuée sans remélangeage à travers des sas de réception (6, 7, 9, 12),
    - dans lequel un premier sas de réception (6) est disposé entre le dispositif d'amenée (2) et le dispositif de mélange (3), afin d'empêcher une communication fluidique entre le dispositif d'amenée (2) et le dispositif de mélange (3), et dans lequel un deuxième sas de réception (7) est disposé entre le dispositif de mélange (3) et le dispositif de traitement final (4), afin d'empêcher une communication fluidique entre le dispositif de mélange (3) et le dispositif de traitement final (4),
    caractérisé en ce que
    - le premier sas de réception (6) et/ou le deuxième sas de réception (7) présentent au moins un organe agitateur.
  2. Module de production (1) selon la revendication 1, caractérisé en ce qu'un contrôle de qualité peut être effectué au moyen de capteurs de qualité dans des conditions constantes à travers le premier sas de réception (6).
  3. Module de production (1) selon l'une quelconque des revendications précédentes, caractérisé en ce que d'autres contrôles de qualité peuvent être effectués au moyen de capteurs de qualité dans des conditions constantes à travers le deuxième sas de réception (7).
  4. Module de production (1) selon la revendication 3, caractérisé en ce qu'un aiguillage (32) est installé entre le deuxième sas de réception (7) et le dispositif de traitement final (4), par lequel un lot (37, 38, 39, 40) peut être évacué.
  5. Module de production (1) selon l'une quelconque des revendications précédentes, caractérisé en ce qu'un troisième sas de réception (9) est disposé entre le dispositif de traitement final (4) et une limite de module (8) du module de production (1), afin d'empêcher une communication fluidique entre le dispositif de traitement final (4) et un environnement du module de production (1).
  6. Module de production (1) selon l'une quelconque des revendications précédentes, caractérisé en ce qu'au moins un principe actif pharmaceutique (17) et au moins un excipient pharmaceutique (18, 19, 20) peuvent être amenés par l'intermédiaire du dispositif d'amenée (2).
  7. Module de production (1) selon l'une quelconque des revendications précédentes, caractérisé en ce que le dispositif d'amenée (2) comprend au moins une unité de dosage (13, 14, 15, 16) pour doser les matières de départ amenées et/ou le dispositif de mélange (3) comprend une installation à lit fluidisé et/ou un granulateur par voie humide et/ou le dispositif de traitement final (4) comprend une presse à comprimés et/ou un remplisseur de capsules (11).
  8. Module de production (1) selon la revendication 7, caractérisé en ce qu'un dispositif de revêtement (10) est monté en aval de la presse à comprimés et/ou du remplisseur de capsules (11), dans lequel un quatrième sas de réception (12) est disposé entre la presse à comprimés et/ou le remplisseur de capsules (11) et le dispositif de revêtement (10), afin d'empêcher une communication fluidique entre la presse à comprimés et/ou le remplisseur de capsules (11) et le dispositif de revêtement (10).
  9. Module de production (1) selon la revendication 2, 3, 4, 5 ou 8, caractérisé en ce qu'au moins un capteur de qualité, par l'intermédiaire duquel une qualité du contenu du premier sas de réception (6) et/ou du deuxième sas de réception (7) et/ou du troisième sas de réception (9) et/ou du quatrième sas de réception (12) peut être détectée par le dispositif de commande (5), est présent à l'intérieur du premier sas de réception (6) et/ou du deuxième sas de réception (7) et/ou du troisième sas de réception (9) et/ou du quatrième sas de réception (12).
  10. Module de production (1) selon l'une quelconque des revendications précédentes, caractérisé en ce que le dispositif d'amenée (2) est relié au dispositif de mélange (3) et/ou le dispositif de mélange (3) au dispositif de traitement final (4) par l'intermédiaire d'un réseau de transport composé de conduites de produit et de soupapes.
  11. Procédé pour la production de formes pharmaceutiques solides avec un module de production (1) selon l'une quelconque des revendications précédentes, caractérisé en ce que des matières de départ (17, 18, 19, 20) sont dosées dans une quantité déterminée avec une très haute précision dans le premier sas de réception (6) au moyen d'unités de dosage (13, 14, 15, 16) du dispositif d'amenée (2), ce qui a pour effet que chaque lot est défini.
  12. Procédé selon la revendication 11, caractérisé en ce que chaque lot est traité séparément dans le dispositif d'amenée (2) et ensuite séparément dans le dispositif de mélange (3) et ensuite séparément dans le dispositif de traitement final (4) et/ou est transporté dans un sas de réception (6, 7, 9, 12) après chaque étape de traitement achevée et contrôlé à cet endroit au moyen de capteurs de qualité en ce qui concerne son aptitude au traitement supplémentaire.
  13. Procédé selon la revendication 11 ou 12, caractérisé en ce que chaque lot est granulé et séché dans le dispositif de mélange (3) uniquement dans une unité de traitement ou granulé dans le dispositif de mélange (3) dans une extrudeuse ou un granulateur haut cisaillement, et ensuite séché dans une unité de traitement du dispositif de mélange (3).
  14. Procédé selon l'une quelconque des revendications 11 à 13, caractérisé en ce que d'autres matières sont amenées dans le deuxième sas de réception (7) avec au moins une unité de dosage supplémentaire (21), afin de mélanger le lot respectif aux autres matières.
  15. Procédé selon l'une quelconque des revendications 11 à 14, caractérisé en ce que des capteurs de qualité contrôlent la qualité dans des unités de traitement individuelles du dispositif de mélange (3) afin de libérer la transmission du lot respectif dans le réseau de transport, ou afin d'évacuer le lot respectif de façon manuelle ou automatique directement en aval ou à partir des unités de traitement du dispositif de mélange (3) dans un contenant à déchets, de sorte que chaque lot, lorsque des paramètres de qualité prédéfinis ne sont pas atteints, est évacué dans un contenant à déchets par l'intermédiaire d'un aiguillage (32) avant d'atteindre le dispositif de traitement final (4).
EP17751038.5A 2016-09-21 2017-07-20 Module de production et procédé pour la fabrication de formes médicamenteuses solides Active EP3515581B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102016218135.1A DE102016218135A1 (de) 2016-09-21 2016-09-21 Produktionsmodul zum Herstellen fester Arzneiformen
PCT/EP2017/068360 WO2018054577A1 (fr) 2016-09-21 2017-07-20 Module de production et procédé pour la fabrication de formes médicamenteuses solides

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EP3515581B1 true EP3515581B1 (fr) 2020-11-25

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US (1) US11478762B2 (fr)
EP (1) EP3515581B1 (fr)
CN (1) CN109789379A (fr)
DE (1) DE102016218135A1 (fr)
ES (1) ES2854980T3 (fr)
WO (1) WO2018054577A1 (fr)

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GB2578272B (en) * 2018-07-10 2023-03-29 Innopharma Res Limited Apparatus and method for the production of solid dosage forms
WO2020105016A1 (fr) * 2018-11-24 2020-05-28 Scitech Centre Production en continu de capsules remplies et procédé associé
DE102019218379A1 (de) * 2019-11-27 2021-05-27 Glatt Ingenieurtechnik Gesellschaft mit beschränkter Haftung Modulare Anlage und Verfahren zur Herstellung von Arzneiformschüttgut
DE102020115777A1 (de) * 2020-06-16 2021-12-16 Fette Compacting Gmbh Verfahren zur Produktverfolgung in einer Anlage
CN114682154A (zh) * 2022-04-29 2022-07-01 山东晨煜石油技术有限公司 一种高温缓蚀剂制备装置及制备方法

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Publication number Publication date
EP3515581A1 (fr) 2019-07-31
DE102016218135A1 (de) 2018-03-22
ES2854980T3 (es) 2021-09-23
US20200016552A1 (en) 2020-01-16
CN109789379A (zh) 2019-05-21
US11478762B2 (en) 2022-10-25
WO2018054577A1 (fr) 2018-03-29

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