Fluidized bed installation

Abstract

Fluidized bed installation (1) comprising - a plurality of granulation units (2) functionally arranged in parallel for the production of pharmaceutical granules, each granulation unit (2) having: • a fluidized bed container (3), • an inlet (4) and an outlet (5) in the fluidized bed container (3), • a fluid feed (6) and a fluid discharge (7) into the fluidized bed container (3), and • at least one injection nozzle (8) for injecting a processing material into the fluidized bed container (3), and - a control unit (12) to adjust the process conditions within each granulation unit (2).

Description

Fluidized bed installation State of the art The invention relates to a fluidized bed system. In particular, the invention relates to a fluidized bed granulation system. Pharmaceutical powders can be processed using either a fluidized bed system or a fluidized bed granulation system. The processing of pharmaceutical powders in fluidized beds is well-established in the art. This includes, in particular, the processes of drying, coating, and granulation. For continuous-operation pharmaceutical wet granulation units, systems with downstream fluidized bed extruders and dryers are currently preferred. However, the changing properties of the granules due to increased compaction in the extruder are a disadvantage in this regard. Wet granulation of pharmaceutical powders in fluidized bed systems has been known since batch-operated systems. However, these systems have not yet been able to operate satisfactorily in fully automatic, continuous, or semi-continuous parallel operation.In particular, no solution is known or accepted in pharmaceutical production that guarantees continuous granulation in such a system and automated or partially automated intermediate cleaning of individual granulation units. Continuously operating fluidized bed granulators are known from chemical and / or food production, constructed as a channel with or without weirs, or with a classifying or non-classifying discharge. However, these systems are not accepted by either the pharmaceutical industry or regulatory authorities. Furthermore, to date, the pharmaceutical industry has lacked adequate process control and the integration of a higher-level overall control system for the fluidized bed granulation unit into a complete production line, as well as the possibility of continuous or semi-continuous parallel granulation and coating. Examples of fluidized bed drying installations with several fluidized bed chambers are shown in documents US 7908765 B2, DE 102013 102133 A1 and DE 102014103661 A1. Another generic prior art is also known from document WO 03 / 033126 A1. Disclosure of the invention The fluidized bed system according to the invention enables fully automatic granulation and drying of pharmaceutical powders. The fluidized bed system comprises a plurality of granulation units arranged in parallel. Each granulation unit is individually loaded through an inlet and emptied through an outlet. Preferably, the granulation unit has an opening through which the inlet and outlet are located. Each granulation unit includes a fluidized bed container, as well as an inlet and an outlet, both of which are located within the fluidized bed container. Furthermore, each granulation unit has a fluid feed and a fluid discharge, also located within the fluidized bed container.A working fluid, particularly air, is introduced into the fluidized bed container via a fluid feed system. There, the working fluid, specifically the air, is mixed with a powdered solid substance introduced through the inlet. The fluid is removed from the fluidized bed container through the fluid discharge port, while the powder or finished product is removed through the outlet port. Additionally, the granulation unit includes at least one injection nozzle for injecting a processing material into the fluidized bed container. The powder within the fluidized bed container can then be coated or granulated with the processing material. A control unit is provided to adjust the process conditions within each granulation unit.Advantageously, process conditions can be adjusted by parameters such as temperature, pressure, or humidity of the fluid fed through the fluid feed. Furthermore, process conditions can be adjusted by the quantity of the fluid fed and / or the quantity of powder or powdered solid fed through the inlet. The adjustment of process conditions within each granulation unit advantageously occurs independently of all other granulation units. With such parallel, automated, and coordinated operation of the individual granulation units, granules can be produced at regular intervals. Fluidized bed containers are advantageously constructed in the shape of a cylinder and comprise a lid and a bottom. A side wall extends between the lid and the bottom. It is particularly advantageous for the fluid feed to be arranged at the bottom and the fluid discharge at the lid, while the inlet and outlet are located on the side surface. In this way, a solid, particularly a powder, introduced into the fluidized bed container through the inlet can be mixed with the working fluid, which is introduced into the fluidized bed container through the fluid inlet and flows within the container to the fluid outlet. The solid to be processed, particularly a powder, thus adopts a fluid-like state.The side surface features a relatively large opening through which the entrance and exit are implemented. The dependent claims contain preferred refinements of the invention. Advantageously, the fluidized bed system is provided with an inlet pipe. This inlet pipe connects all the inlets of all the granulation units. The inlet pipe may also lead to a central distribution system. It is particularly advantageous for the granulation units to be arranged in a ring, so that the inlet pipe is annular. Alternatively, the granulation units are preferably arranged linearly in at least one row, so that the inlet pipe is also linear. Each inlet is advantageously connected to the inlet pipe via a valve, so that each fluidized bed container of each granulation unit can be filled separately through the inlet pipe. It is particularly advantageous for there to be exactly one inlet pipe, especially in an annular shape.Alternatively, the inlet duct may also preferably comprise an individual duct for each granulation unit. The inlet duct is also preferably connected to a waste collection device by means of which excess and / or defective material can be collected. Alternatively, each individual duct may be connected directly, without a valve, to the inlet of a waste collection device. Furthermore, the fluidized bed system is preferably designed to have an outlet pipe. All the outlets of all the granulation units are connected via this outlet pipe. Again, it is preferably designed to have the granulation units arranged in a ring, so that the outlet pipe is an annular pipe. Alternatively, the arrangement can also be linear, so that the outlet pipe also runs linearly. Each outlet is advantageously connected to the outlet pipe via its own valve, so that individual granulation units can optionally be emptied. The outlet pipe is also advantageously connected to a waste collection device. In this way, the excess material can be collected and preferably disposed of via the waste collection device.The waste collection device may be the same waste collection device described above. It is particularly advantageous for both the inlet and outlet ducts to be ring-shaped, although the ducts may also have other shapes, in particular running linearly. The inlet and / or outlet duct may also be configured as an annular segment. In another particularly preferred embodiment, the granulation units are arranged in a ring shape, with the inlet duct at least partially enclosing the granulation units on the outside, while the outlet duct is arranged, at least as an annular segment, within the annularly arranged granulation units. This ensures a space-saving structure.A linear arrangement of the granulation units allows for easy access to each individual unit within the fluidized bed system. This, in particular, facilitates simple manual cleaning. In an advantageous embodiment, the fluidized bed system comprises a cleaning module. The cleaning module is operatively connected to each granulation unit. Particularly advantageous is the presence of an annular or segmented cleaning conduit connecting the fluidized bed containers of all the granulation units. This allows each granulation unit to be cleaned by the cleaning module. Again, it is particularly advantageous to have valves connecting each fluidized bed container to the cleaning conduit. This ensures that one granulation unit can be cleaned independently of the others. In particular, this also allows one granulation unit to be cleaned while others remain in operation. The cleaning module is particularly advantageously configured for cleaning with subsequent manual intervention. This type of cleaning is also known as Wipe In Place (WIP). Alternatively, the cleaning module is also advantageously configured for cleaning without subsequent manual intervention. This type of cleaning is also known as Clean in Place (CIP). The fluidized bed system can therefore be cleaned at least partially in an automated manner by the cleaning module, with the cleaning affecting only individual granulation units within the plurality of granulation units. Therefore, production using the fluidized bed system is either unaffected or only slightly affected by the cleaning process. The fluidized bed system preferably has at least one module inlet. This module inlet is connected to the inlets of all the granulation units. The previously described inlet duct is particularly advantageous, as the module inlet is connected to it. The module inlet can be controlled by the control unit. Therefore, the control unit is a central entity not only for controlling the individual granulation units but also for controlling the module inlet. Consequently, the granulation process can be carried out safely and reliably within the granulation units, since all preparation parameters are known. The module inlet can be, in particular, a central distribution module and / or a diverter and / or a null conduit and / or a switching valve and / or an intermediate storage container. In this way, the optimal quantity required for one of the granulation units can always be available and fed to the granulation unit. Alternatively or additionally, the preparation module can include an inlet mill and / or an inlet scale. Furthermore, the fluidized bed system is preferably provided with at least one module outlet. The module outlet is connected to the outlets of all the granulation units. The previously described outlet conduit is particularly advantageous, as the module outlet is connected to it. The module outlet can be controlled by the control unit. Finally, the injection nozzle is preferably arranged in the bottom, lid, and / or side wall of the granulation unit. Multiple injection nozzles are particularly advantageous. A processing material, in particular a granulation liquid, can be injected into the fluidized bed container through the injection nozzles, allowing the powder inside the container to be granulated or otherwise processed, particularly by coating.This allows, in particular, the production of pharmaceutical agents. Several injection nozzles can be arranged particularly advantageously, especially in different locations within the granulation unit and / or the fluidized bed container. The invention also relates to a process for the semi-continuous production of granules, particularly pharmaceutical granules, within a fluidized bed system. In this regard, the individual granulation units of the fluidized bed system are designed to operate individually and / or independently of one another. Furthermore, it is preferably designed that the individual granulation units can be cleaned independently of the operation of the other granulation units. This allows for uninterrupted operation of the fluidized bed system. Brief description of the drawing(s) The following section describes in detail examples of embodiments of the invention with reference to the accompanying drawing. In the drawing: Figure 1 is a schematic illustration of a granulation unit of a fluidized bed installation according to an example embodiment of the invention, Figure 2 is a schematic illustration of an alternative granulation unit of a fluidized bed installation according to the embodiment of the invention, Figure 3 is a schematic illustration of a fluidized bed installation according to the example of embodiment of the invention in a second alternative, Figure 4 is a first alternative of an inlet module of a fluidized bed installation according to the embodiment of the invention, Figure 5 is a second alternative for an inlet module of a fluidized bed installation according to the embodiment of the invention, Figure 6 is a third alternative for an inlet module of a fluidized bed installation according to the embodiment of the invention, Figure 7 shows alternatives for an outlet module of a fluidized bed installation according to the embodiment of the invention, Figure 8 is a first alternative arrangement of the granulation units of the fluidized bed installation according to the embodiment of the invention, Figure 9 is a second alternative arrangement of the granulation units of the fluidized bed installation according to the embodiment of the invention, Figure 10 is a third alternative arrangement of the granulation units of the fluidized bed installation according to the embodiment of the invention, and Figure 11 is another schematic illustration of a part of the fluidized bed installation according to the embodiment of the invention. Figure 1 shows a granulation unit 2 of a fluidized bed installation 1 (compare Figures 2 and 3) according to an exemplary embodiment of the invention. A fluid, in particular a gas, and preferably air, is supplied to the granulation unit 2 via an air treatment installation (not shown) with a heat exchanger, filter, and external air supply. The gas is supplied to the granulation unit 2 via a fluid feed 6, the fluid feed 6 being arranged in a bottom 15 of the granulation unit 2. In particular, a disc-shaped gas distribution bottom (30) is arranged above the bottom 15, which distributes the supplied air over a large area across the entire cross-section of the fluidized bed container 3. The bottom 15 is circular and encloses a hollow cylindrical fluidized bed container 3. The fluidized bed container 3 is further enclosed by a similarly circular lid 16. The side walls 17 of the fluidized bed container 3 therefore extend between the bottom 15 and the lid 16. The bottom 15 and the lid 16 are arranged parallel to each other. In parallel, below the cover 16, a disc-shaped filter bottom 29 is provided. This filter bottom 29 comprises and carries at least one filter 27, which is arranged at a fluid outlet 7. The gas introduced into the bottom 15 through the fluid inlet 6 can thus be removed from the granulation unit 2 via the filter 27 and through the fluid outlet 7. In this way, a fluid flow, in particular a gas flow, can be generated within the fluidized bed container 3. Furthermore, the granulation unit 2 has injection nozzles 8, which protrude into the interior of the fluidized bed container 3. In Figure 1, the injection nozzles are configured as side spray nozzles. Alternatively or additionally, the injection nozzles 8 can be arranged within the bottom 15 (bottom spray) and / or within the cover 16 (top spray).The injection nozzles supply a processing material, in particular a granulation liquid, for use in the process within the fluidized bed container 3. The space enclosed by the fluidized bed container 3 between the bottom 15 and the lid 16, specifically between the gas distribution bottom 30 and the filter 27, forms the process space through which the gas, introduced via the fluid inlet 6, flows. The process space extends from a central axis of the fluidized bed container 3 to the side wall 17 and is created with rotational symmetry, advantageously in a cylindrical shape. A powdered solid can be introduced into the process space through an inlet 4 extending through the side wall 17.A finished product, in particular a dry granule, can be removed from the fluidized bed container 3 through an outlet 5, which also extends through the side wall 17. The powdered solid and the granule are preferably transported pneumatically into and out of the granulation unit by suction conveying, or alternatively gravimetrically with suitable equipment. The gas flowing through the process space, from fluid inlet 6 at the bottom 15 to fluid outlet 7 at the top 16, puts the powdered solid introduced into the process space through inlet 4 into a fluid-like state of motion. This results in intense heat exchange and mass transfer, facilitated by a very thorough mixing process. This mixing process also allows the fluidized powder in the process space to mix with a granulating liquid sprayed into the space through injection nozzles 8. The mixing of the fluidized powder with the sprayed granulating liquid allows several individual powder particles to agglomerate into larger particle clusters (agglomerates).Due to the intense simultaneous heat transfer, a large portion of the granulation liquid evaporates from the surface of the agglomerate and, to some extent, from within the agglomerates' pores, causing them to dry. However, some liquid remains within the agglomerates, allowing the individual particles to adhere to one another. The resulting agglomerate is called granules. As described above, the granulation liquid can be fed into the process space in different ways. In particular, top spray, bottom spray, and side spray procedures can be used. Advantageously, the 8 injection nozzles are nozzles for three substances. The fluidized bed granulation process within each granulation unit 2 is monitored by measuring equipment (not shown) in the supply and exhaust air ducts connecting the fluid inlet 6 to an air supply and the fluid outlet 7 to an air exhaust, above and below the bottom 15, in the process space, and before and after the filter 27. In this respect, the measuring equipment advantageously determines data on the gas mass flow rate between the fluid inlet 6 and the fluid outlet 7, the gas moisture content, the gas and solid temperatures, the pressure drop within the bottom 15 (preferably configured as an air distribution bottom) and at the filter 27, and optionally the particle size distribution and product moisture content. This data is transmitted to a control unit 12 (cf.Figure 3) of the fluidized bed installation 1. A top-level control unit 12 is intended to be used for all the granulation units 2. The control unit 12 can be used to influence corresponding adjustment actuators of the individual granulation units 2, enabling stable and reliable operation of the process within predefined process limits. To this end, valves can be appropriately adjusted to control material transport through inlet 4 and outlet 5, to control fluid flow, particularly gas flow, between fluid inlet 6 and fluid outlet 7, and to control a cleaning system. The functionality of the cleaning system, specifically a cleaning module 11, is described below with reference to Figure 2. Figure 2 shows an alternative embodiment of the granulation units 2 of the fluidized bed installation 1. The alternative embodiment is identical to the embodiment shown in Figure 1, with the only difference between Figure 1 and Figure 2 being the inlet 4 and outlet 5. In Figure 1, there is a separate opening for inlet 4 and outlet 5 in the lateral surface 3. In the alternative shown in Figure 2, there is a single opening within the lateral surface 3, with inlet 4 and outlet 5 being implemented through this common opening in the lateral surface 3. Figure 3 shows a first alternative of a fluidized bed installation 1 according to the embodiment of the invention. The fluidized bed installation 1 shown has five granulation units 2. The fluidized bed installation 1 has, in particular, at least two, and especially advantageously up to ten or more individual granulation units 2. All the granulation units 2 can operate in parallel. In this respect, it is preferably provided that at least one granulation unit remains in standby mode until it is activated. The granulation installation 1 also has equipment for the removal of waste material. Such a waste collection device 23 advantageously serves to collect both the waste material within the powdered solid to be fed to the granulation units 2 and within the finished granules. The individual granulation units 2 preferably have a common air supply 24. The air supply 24 is connected to all fluid inlets 6 of the granulation units 2. However, it is preferably provided that, via the control unit 12, the quantity and / or humidity and / or temperature of the inlet gas flowing through the fluid inlet 6 of each granulation unit 2 can be individually adjusted. Alternatively, each granulation unit 2 may have its own air supply 24. The fluidized bed system 1 also features a cleaning module 11. Specifically, the cleaning module enables cleaning without subsequent manual intervention (Clean in Place, CIP) or, alternatively, cleaning with subsequent manual intervention (Wipe in Place, WIP). The cleaning module is connected to each granulation unit 2 via a cleaning conduit 28 for fully automated cleaning. For this purpose, the connection is advantageously permanent, although it can also be established for cleaning purposes only.The cleaning conduit 28 is preferably connected to each individual granulation unit 2 via valves and, when required and selectively, ideally supplies a cleaning medium to one or more cleaning nozzles advantageously arranged on the side wall 17 and / or the fluid inlet 6 and / or the fluid outlet 7 and / or the lid 16 and / or the filter bottom 29 and / or the bottom 15 and / or the inlet 4 and / or the outlet 5 and / or the feed conduit 9 and / or the outlet conduit 10 and / or the module inlet 13 and / or the module outlet 14 and / or the main inlet 19, these valves being controllable by the control unit 12. Therefore, each granulation unit 2 can be cleaned individually by the control unit 12 without affecting the operation of the other granulation units 2. The fluidized bed installation 1 further comprises a conduit 9, which is configured as a ring segment or annular shape. The inlet conduit 9 surrounds the annularly arranged granulation units 2 and connects all the inlets of the granulation units 2. Each inlet 4 of a granulation unit 2 is connected to the inlet conduit 9 via a valve that can be controlled by the control unit 12. Therefore, the control unit 12 can be used to determine which granulation unit 2 should be fed with a powdered solid. The inlet conduit 9 is also connected to the waste collection device 23 for the purpose of transferring unsuitable material to the waste collection device 23.In this case as well, a valve is provided between the waste collection device 23 and the inlet conduit 9, this valve being controllable by the control device 12. Finally, the inlet conduit 9 is provided to be connected to a module inlet 13. The inlet conduit 9 can be filled with a material, in particular a powdered solid, through the module inlet 13. The fluidized bed installation 1 also features an outlet pipe 10. The outlet pipe 10 is configured as a ring segment and is enclosed by the annularly arranged granulation units 2. The outlet pipe 10 connects the outlets 5 of all the granulation units 2. This connection is made via its own valve in each case, each valve being controllable by the control device 12 independently of any other valve. The outlet pipe 10 is also connected to the waste collection device 23 for the disposal of waste material from the granules produced in the granulation units 2. This device also preferably includes a valve controllable by the control unit 12. Finally, the outlet pipe 10 is connected to a module outlet 14.Again in this case, a valve is preferably present, the valve being controllable by control unit 12. With control unit 12, the fluidized bed installation 1 features a superior level general control equipment which, in addition to the plurality of granulation units 2, also controls, in particular, the preparation module 13 and the cleaning module 11. Preferably, a transport air supply 25 is also present. The transport air supply 25 allows the granules to be pneumatically removed from the granulation units 2 by sucking the granules into the outlet duct 10. This is the purpose of the transport air supply 25. The transport air supply 25 also ensures that the granules can be transported to the outlet of module 14. The following describes, by way of example, how the fluidized bed installation 1 can be used: The granulation units 2 are pneumatically filled in series with powdered solid, successively at intervals of at least ten to 600 seconds or more, using the air supply 24. In this respect, the airflow within each granulation unit 2 generates suction, by means of which the powdered solid can be drawn into the fluidized bed container 3. Alternatively, the granulation units 2 can be filled gravimetrically. As soon as the filling process of an individual granulation unit 2 is complete, fluidized bed granulation begins in that unit 2.The granules are also emptied pneumatically from the granulation units 2 using the transport air supply 25, when the granulation unit ceases to generate suction and the transport air supply 25 creates suction towards the outlet duct 10. Alternatively, emptying can also be carried out gravimetrically. Emptying takes place sequentially at the same time interval as filling, with the order and time interval for emptying individual granulation units 2 corresponding to the filling order. Each granulation unit 2 is preferably refilled with powdered solid immediately after emptying. The emptying time can alternatively be determined by reaching a termination criterion (temperature or humidity in the process space) for the granulation and drying process. After a granulation unit 2 has been filled and emptied once, one cycle of that granulation unit 2 is complete. Each granulation unit 2 can be operated for several cycles without cleaning, depending on the material. After a predefined maximum number of cycles is reached, the control device 12 initiates either fully automatic cleaning or pre-cleaning of the respective granulation unit 2 using the cleaning module 11. After the cleaning or pre-cleaning is complete, the granulation unit 2 can be put back into operation directly or, if necessary, finished manually. The cleaning process using the cleaning module 11 is carried out in such a way that the other granulation units 2 can continue operating during this time. The top-level general control equipment in the form of control unit 12 controls the air supply 24 for the process gas, i.e., the fluid that is fed to each granulation unit 2 via the fluid feed 6, as well as the transport air supply 25. In addition, the general control equipment in the form of control unit 12 controls all valves for product transport and / or material transport that are connected to the inlet duct 9 and / or the outlet duct 10. Finally, the general control equipment in the form of control unit 12 controls the cleaning module 11 as well as all the adjustment actuators that influence the fluidized bed granulation process in the individual granulation units 2.This ensures that process parameters remain stable and reliable within predefined process limits, making fluidized bed granulation highly safe and reliable. Furthermore, the overall control equipment, in the form of control unit 12, monitors the fluidized bed installation 1, recording and evaluating all measurement data from the sensors located in the granulation units 2. This measurement data can then be presented to a user via a human-machine interface. This allows for the rapid identification of potential technical issues that could lead to technical failures or quality fluctuations in the process. In particular, the time evolution of the pressure drop over the gas distribution bottom 30 of each granulation unit 2 or over the filter 27 of each granulation unit 2 is relevant in this regard.If a temporary increase in this parameter is detected and identified as problematic, control unit 12 can autonomously decide which granulation unit 2 should be automatically cleaned next and / or send a message to the user indicating that cleaning is required. Monitoring the spray rate of the granulation liquid via the injection nozzles 8 can also be used as an indicator of the condition of the injection nozzles 8 or the ducts located behind them. Therefore, the granulation plant 1 can autonomously monitor and optimize its technical status, minimizing downtime. Figure 4 schematically shows a first alternative for a module 13 inlet. The module 13 inlet is configured as a diverter 18. In the example shown in Figure 4, the diverter 18 has a plurality of individual outlets 21 which together form the inlet duct 9. Each individual outlet 21 can be connected separately to a general inlet 19. Figure 4 shows three different ways to do this, according to which each individual outlet 21 can be connected to the general inlet 19. The inlet duct 9 thus comprises a plurality of individual ducts connecting each individual outlet 21 to a granulation unit 2. Figure 5 schematically shows a second alternative for the module 13 inlet. In this configuration, the module 13 inlet is configured as a switching unit 22. As in the example shown in Figure 4, there is again a plurality of individual outlets 21, the individual outlets 21 together forming the inlet conduit 9. Therefore, it is again preferably arranged that each individual outlet 21 is connected separately to a granulation unit 2. Each individual outlet 21 can be individually connected to the main inlet 19 via the switching unit 22. Figure 6 schematically shows a third alternative for the module 13 inlet. In this case, the module 13 inlet comprises a central distributor 26 having a plurality of individual valves 20. Each individual valve 20 is connected to the main inlet 19 via the central distributor 26.Each individual valve 20 controls an individual outlet 21, each individual outlet 21 being connected in turn to exactly one granulation unit 2. Thus, by controlling each individual valve 20, the associated granulation units 2 can be connected to the general inlet 19. Figure 7 schematically shows two preferred alternatives for a module outlet 14 of the fluidized bed installation 1. On the one hand, a linear outlet conduit 10 can be used, connected to the module outlet 14. This is particularly advantageous when the granulation units 2, and in particular any waste collection device 23 that may be present, are arranged in series, i.e., in a row. Alternatively, the outlet conduit 10 can be U-shaped, as shown in Figure 7, if the granulation units 2, and in particular any waste collection device 23 that may be present, are arranged along two or more rows. The module outlet is, in turn, preferably connected to the outlet conduit 10. Figures 8 to 10 show examples of alternative arrangements to the annular arrangement of the granulation units 2 shown in Figure 3. Thus, in Figures 8 to 10, the fluidized bed installations 1 are represented only by the granulation units 2. The other components shown in Figure 3 are not shown in Figures 8 to 10 for clarity. Figure 8 shows a schematic arrangement of the fluidized bed system 1, with the granulation units 2 arranged in columns. This has the particular advantage that each granulation unit 2 is easily accessible from the outside, allowing for easy access for maintenance and / or manual cleaning. In Figure 9, the granulation units 2 form two parallel columns. Finally, Figure 10 shows the granulation units 2 arranged in a row. This configuration also offers the advantages described above regarding accessibility and simplified maintenance and / or manual cleaning. It is also possible to arrange several granulation units 2 in a parallel row. Figure 11 shows another alternative for a fluidized bed installation 1 according to the embodiment of the invention. The granulation units 2 are arranged in a semicircle on a polygonal technical wall 31 that resembles a semicircle. The inlet 4 and outlet 5 are oriented towards the technical wall 31. The powder inlet 4 of each granulation unit 2 is connected to its own inlet duct 9 through the technical wall 31. Each inlet duct 9 is connected to the inlet of module 13. The general powder inlet 19 is connected to the inlet of module 13.The outlet 5 of each granulation unit is connected to outlet duct 10. A shut-off valve 32 is advantageously interposed to allow for maintenance work on outlet 5 of granulation unit 2 when necessary, while the other granulation units 2 are in operation and, if applicable, while product is being conveyed through outlet duct 10. Outlet duct 10 conveys the product to the outlet of module 14. The waste collection device 23 is connected either via inlet duct 9 to the inlet of module 13 or, alternatively, to outlet duct 10, ideally to the outlet of module 14. The control unit 12, air supplies 24 and 25, and cleaning system 11 are not shown for clarity. The fluidized bed installation 1 offers the following advantages: - no scaling up of laboratory tests to production processes is necessary, as the facility can be used for both purposes, - a single inlet for a plurality of pharmaceutical powders at the inlet of module 13, - 100% traceability of each batch, - absence of cross-contamination between individual batches, as the granulation units 2 operate completely separately and independently from each other, - Individual granulation units 2 can be automatically cleaned during the operation of the other granulation units 2 without the need to open the fluidized bed installation 1; alternatively, the granulation units 2 can be pre-cleaned, so that subsequent manual cleaning must take place; in either case, the cleaning and / or pre-cleaning is carried out during the ongoing operation of the other granulation units 2, - The fluid supply, in particular the air supply, to each granulation unit 2 can be regulated individually and independently; specific parameters can be configured for each granulation unit 2, such as air quantity, air humidity and air temperature, - supply of the 2 individual granulation units, as well as the discard container, preferably through individual annular conduits, the annular conduits being configured in the form of a ring or in the form of a ring segment, - possibility of sluice gate discharge before and after fluidized bed granulation, - The inlet duct 9 and outlet duct 10 described reduce the number of valves required and increase process flexibility, - Various options for spraying processing substances, particularly granulation liquids: top spray, bottom spray, side spray, - integration into a control concept and / or regulation concept of the granulation units 2, which means • upper level regulation equipment for integrating the 2 individual granulation units into the fluidized bed installation 1, • Implementation of a closed-loop control system with a top-level regulating equipment for the 2 individual granulation units. - A coordinated and efficient process analytical technology (PAT) concept across all granulation units 2 • Continuous process verification (CVP) • virtual sensor modeling (soft sensor modeling) • Process analytical technology (PAT) • Statistical process control (SPC) through multivariate data analysis (MVDA) and univariate data analysis • Database system for data management, data collection, and data evaluation - Automatic identification of any technical problems that may arise in the individual granulation units 2 and notification to the user, presentation of recommendations and, advantageously, autonomous action, in particular cleaning, to prevent more serious problems, - minimizing downtime and the amount of waste material, - development and production in a single facility, - Automatic execution of test programs (DoE, etc.) through a complete fluidized bed calculation process according to a user's specifications • various formulations • various fill quantities • various operating parameters

Claims

1. A fluidized bed installation (1) comprising: a plurality of granulation units (2) functionally arranged in parallel for the production of pharmaceutical granules, each granulation unit (2) having: a fluidized bed container (3), an inlet (4) and an outlet (5) in the fluidized bed container (3), a fluid feed (6) and a fluid discharge (7) in the fluidized bed container (3), and at least one injection nozzle (8) for injecting a processing material into the fluidized bed container (3), and a control unit (12) for adjusting the process conditions within each granulation unit (2).

2. A fluidized bed installation (1) according to claim 1, characterized by an inlet conduit (9) through which the inlets (4) of all the granulation units (2) are connected. 3.A fluidized bed installation (1) according to any of the preceding claims, characterized by an outlet conduit (10) through which the outlets (5) of all the granulation units (2) are connected.

4. A fluidized bed installation (1) according to any of the preceding claims, characterized by a cleaning module (11) that is operatively connected to each granulation unit (2) and by which each granulation unit (2) can be cleaned independently of any other granulation unit (2).

5. A fluidized bed installation (1) according to claim 4, characterized in that the cleaning module (11) is configured to carry out cleaning with subsequent manual intervention or cleaning without subsequent manual intervention. 6.A fluidized bed installation (1) according to any of the preceding claims, characterized by at least one module inlet (13), the module inlet (13) being connected to the inlets (4) of all the granulation units (2) and the module inlet (13) being controllable by the control unit (12).

7. A fluidized bed installation (1) according to claim 6, characterized in that the module inlet (13) is configured as a central distribution module (18) and / or intermediate storage module and / or switching valve and / or diverter and / or annular conduit.

8. A fluidized bed installation (1) according to any of the preceding claims, characterized by at least one module outlet (14), the module outlet (14) being connected to the outlets (5) of all the granulation units (2) and the module outlet (14) being controllable by the control unit (12). 9.Fluidized bed installation (1) according to any of the preceding claims, characterized in that at least one injection nozzle (8) is arranged in a bottom (15) and / or in a lid (16) and / or in a side wall (17) of the granulation unit (2).

10. Method for the semi-continuous production of pharmaceutical granules in a fluidized bed installation (1) according to claim 1, characterized in that the granulation units (2) of the fluidized bed installation (1) are operated and / or cleaned independently of each other.

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