Coating apparatus unit and method for producing granules that are functionally coated with a coating agent

Abstract

The invention relates to a coating apparatus unit (1) for producing granules (6) that are functionally coated with a coating agent (5), and to a method for producing granules (6) that are functionally coated with a coating agent (5).

Description

[0001] ADD Advanced Drug Delivery Technologies Ltd.

[0002] Coating apparatus unit and method for producing functionally coated with a coating agent

[0003] Granules

[0004] The invention relates to a coating apparatus unit for producing granules functionally coated with a coating agent, with a coating apparatus for coating the granules with the coating agent, wherein the coating apparatus has a coating chamber and a spray device arranged in the coating chamber for spraying the coating agent, and wherein in the coating chamber the granules having an active substance content can be or are coated by the spray device in a coating process with a quantity of coating agent to form a layer having a layer thickness, and wherein the coating apparatus unit has a process analysis tool and an electronic evaluation unit.

[0005] The invention further relates to a method for producing granules functionally coated with a coating agent, comprising a coating apparatus unit with a coating apparatus for coating the granules with the coating agent, wherein the coating apparatus has a coating chamber and a spray device arranged in the coating chamber for spraying the coating agent, and wherein in the coating chamber, the granules having an active ingredient content are coated in a coating process by the spray device with a quantity of coating agent to form a layer having a layer thickness, and wherein the coating apparatus unit has a process analysis tool and an electronic evaluation unit. Granules are ideal dosage forms for achieving specific active ingredient release profiles.Due to their round shape, smooth surface, and narrow particle size distribution, they can easily be functionally coated, for example, to achieve taste masking, enteric-coated protection, or the release of the active pharmaceutical ingredient (API) in specific areas of the gastrointestinal tract. The release profile depends on the amount of coating agent applied, which determines the layer thickness of the functional coating itself. Granules are defined here as powdery, granular, or lumpy mixtures that are in a pourable form (bulk material), preferably materials consisting of particles, such as granulated particles, agglomerates, pellets, or tablets.In an unpublished prior art, the coating is carried out using a predetermined amount of coating agent, which is evenly applied to the granules to be coated during the coating process so that a desired active ingredient release profile can be achieved. After the coating process, the active ingredient in the granules is then determined in the laboratory by analytical content determination as a quality control measure. The layer thickness is usually not determined. The quality of the functional coating can be assessed from the ratio of theoretical to practical active ingredient content. In addition, a release test is carried out in which the proportion of active ingredient released is measured over time. There is usually a relationship between the amount of coating agent applied, which determines the layer thickness, and active ingredient release.As the amount of coating agent applied increases, the active ingredient content in the granules decreases. Such quality control is very time-, cost-, and personnel-intensive. The object of the invention is therefore to provide a coating apparatus unit and a method for producing granules functionally coated with a coating agent, which overcome the disadvantages known from the prior art and enable the determination of the amount of coating agent applied to the granules by means of the sprayed coating agent, and thus the layer thickness of the applied layer, during the coating process.This task is achieved in a coating apparatus unit of the type mentioned above in that the process analysis tool is suitable for measuring the active ingredient content of the granules, which is transmitted to the evaluation unit, so that the mass increase of the granules by means of the coating agent applied to the granules can be determined in the evaluation unit, taking into account the measured active ingredient content of the granules. Advantageously, the preferred coating apparatus unit makes it possible to determine the mass increase of the coating applied to the granules by means of the sprayed coating agent, and thus to influence the coating process and adapt it accordingly in order to obtain an optimal active ingredient release profile for the produced granules.Furthermore, it is relatively easy for the strictly regulated pharmaceutical industry to integrate the coating unit into existing processes for the production of coated granules, thereby further optimizing them. Offline or online measurement of the active ingredient content, for example, during a coating process, is essential for determining the mass increase of the granules, since the active ingredient content decreases with increasing mass of the functional coating applied to the granules. Thus, it is now possible to produce granules that, in addition to a defined active ingredient content, also have a coating layer applied to the granules with an optimal thickness for a desired drug release profile.According to an advantageous embodiment of the coating apparatus unit in this regard, the evaluation unit is part of a control device having a control functionality that is configured to regulate and / or control the coating process taking into account the measured active ingredient content. The advantage of regulating and / or controlling the coating process taking into account the measured active ingredient content is that an optimal active ingredient release profile can be generated on the granules. The regulation and / or control of the coating process can also be carried out taking into account the specific layer thickness. Here, too, an optimal active ingredient release profile is achieved through the optimally coated granules.According to a further advantageous embodiment of the coating apparatus unit in this regard, the control device is further configured to determine a control deviation between a target active ingredient content value and the active ingredient content measured as the actual active ingredient content value, and to use the determined control deviation to determine a manipulated variable and transmit this to the spraying device. It is equally possible to determine the control deviation between the target layer thickness value and the layer thickness determined as the actual layer thickness value, and to use the determined control deviation to determine a manipulated variable and transmit this to the spraying device. In both cases, it is possible to produce functionally coated granules with an optimal layer thickness, which in turn has an optimal active ingredient release profile.According to a further development of the coating apparatus unit, the spraying device is configured to be or be regulated by the control variable transmitted from the control device to the spraying device. Preferably, the spraying device is configured so that an atomizing gas pressure of the spraying device or the spraying rate of the spraying device is or is regulated by the control variable of the control device. Due to the advantageously designed coating apparatus unit having a control device, it is now possible to record the active ingredient content inline during the coating process using the process analysis tool and to influence the layer thickness of the layer applied to the granules during the manufacturing process via the control device connected to the spraying device.The droplet size of the sprayed droplets is preferably regulated by adjusting the atomizing gas flow in the spraying device or by adjusting the spray rate, i.e., the volume flow of the at least one liquid to be sprayed, in the spraying device. According to an additional advantageous embodiment of the coating apparatus unit, the control device has an active ingredient content tolerance value and is configured to produce the granules with an active ingredient content within the active ingredient content tolerance value. It is also possible to store a layer thickness tolerance value in the control device and, with the appropriate control of the spraying device, to obtain granules with a defined active ingredient content and, at the same time, with a layer thickness that is optimal for a specific active ingredient release profile.This allows the coating process to be carried out even more effectively, since the coating process only needs to achieve a predefined level of accuracy. According to a further development of the coating apparatus unit, the spray device has at least one spray element. In this regard, the spray element is designed as a multi-component nozzle. The spray device is expediently designed as a head and / or bottom spray unit and / or tangential spray unit. Preferably, the spray device has at least one spray element. Particularly preferably, the spray element is designed as a multi-component nozzle. Most particularly preferably, the spray device is designed as a head and / or bottom spray unit. This makes it possible to optimally spray the solid particles in the solid particle bed of the fluidization chamber at all times and thus treat them more effectively.According to a preferred development of the coating apparatus unit, the coating apparatus is designed as a drum coater or as a fluidization apparatus, wherein the fluidization apparatus is expediently designed as a fluidized bed or spouted bed apparatus. According to an additional advantageous embodiment of the coating apparatus unit, the process tool is designed as a measuring device for the spectrally spatially resolved recording of the VIS-NIR absorption spectra, expediently as a VIS-NIR hyperspectral camera. The measuring device is preferably configured to record VIS-NIR absorption spectra in a wavelength range between 250 nm and 2700 nm, expediently between 550 nm and 1700 nm. Surprisingly, it has been found that the active ingredient content can be optimally recorded in these wavelength ranges.Further preferably, the coating apparatus unit is designed such that the coating apparatus comprises the process analysis tool, wherein the process analysis tool is expediently arranged in the coating chamber or a coating chamber bypass. Such an arrangement of the process analysis tool enables optimal detection of the active ingredient content during the coating process. Furthermore, process analysis tools arranged in the coating chamber bypass are not directly exposed to the coating agent and therefore have a longer service life and improved detection properties. Furthermore, the evaluation unit is preferably connected to the process tool, expediently via a data line. This enables automated evaluation.According to an additional advantageous embodiment of the coating apparatus unit, the evaluation unit is configured to determine the layer thickness of a coating agent applied to the granules from the mass increase of the granules. Such knowledge of the layer thickness further improves the active ingredient release profile, and the coating layer thickness does not require laborious recording in a downstream quality control step. Furthermore, this task is achieved in a method of the type mentioned above in that the process analysis tool measures the active ingredient content of the granules and transmits this to the evaluation unit, so that the mass increase of the granules is determined in the evaluation unit using the coating agent applied to the granules, taking into account the measured active ingredient content of the granules.The preferred method advantageously makes it possible to indirectly measure the layer thickness of the coating agent applied to the granules using the sprayed coating agent in the coating apparatus using the active ingredient content, thus influencing the coating process and adapting it accordingly to achieve an optimal active ingredient release profile for the produced granules. Online measurement of the active ingredient content during a coating process is essential for determining the layer thickness, since the active ingredient content decreases with increasing layer thickness of the functional coating applied to the granules. Thus, it is now possible to provide a method that, in addition to a defined active ingredient content, also produces an optimal layer thickness for a desired active ingredient release profile for a layer of a coating agent applied to the granules.In this regard, the evaluation unit is advantageously part of a control device having a control functionality that regulates and / or controls the coating process taking into account the measured active ingredient content. The control device preferably ends the coating process when a desired active ingredient content of the granules is reached. According to an advantageous embodiment of the method, the control device regulates the coating process taking into account the measured active ingredient content by determining a control deviation between a target active ingredient content value and the active ingredient content measured as the actual active ingredient content value, and using the determined control deviation to determine a manipulated variable, which is then transmitted to the spraying device.In a method advantageous in this regard, the spray device is configured to be controlled by the manipulated variable transmitted from the control device to the spray device. Preferably, the spray device is configured so that an atomizer gas pressure of the spray device or the spray rate of the spray device is controlled by the manipulated variable of the control device. Here, too, the regulation and / or control of the preferred method produces optimally coated granules, which in turn have an optimal active ingredient release profile. The regulation and / or control of the method does not necessarily have to be carried out by means of the measured active ingredient content, but can also be carried out by means of the determined layer thickness of the layer applied to the granules.According to a further advantageous embodiment of the method, the control device has an active ingredient content tolerance value and is configured to produce the granules with an active ingredient content within the active ingredient content tolerance value. It is also possible to store a layer thickness tolerance value in the control device and, with the appropriate control of the spray device, to obtain granules with a defined active ingredient content and, at the same time, with a layer thickness that is optimal for a specific active ingredient release profile. By specifying a tolerance value, it is possible to effectively regulate and / or control the coating process, for example, by terminating the coating process when a value within the tolerance range is reached.Further preferably, the process tool is designed as a measuring device for the spectrally resolved detection of the VIS-NIR absorption spectra, expediently as a VIS-NIR hyperspectral camera, wherein VIS-NIR absorption spectra are detected in a wavelength range between 250 nm and 2700 nm, expediently between 550 nm and 1700 nm. Surprisingly, it has been found that the active ingredient content can be optimally detected in these wavelength ranges. According to a further advantageously designed method, the evaluation unit determines the layer thickness of a coating agent applied to the granules from the increase in mass of the granules. Such a method further improves the active ingredient release profile, and the layer thickness of the coating does not require complex determination in a downstream quality control step.The invention is explained in more detail below with reference to the accompanying drawing, in which: Figure 1 shows a schematic representation of a first embodiment of a coating apparatus unit with a coating apparatus designed as a fluidized bed apparatus and a spray device designed as a head spray unit, Figure 2 shows a schematic representation of a second embodiment of a coating apparatus unit with a coating apparatus designed as a fluidized bed apparatus and a spray device designed as a bottom spray unit, and Figure 3 shows a scatter diagram of the predicted active ingredient content versus the measured active ingredient content. Unless otherwise stated, the following description refers to all embodiments of a coating apparatus unit 1 illustrated in the drawing for producing granules functionally coated with a coating agent. Fig.1 shows a schematic representation of a first embodiment of a coating apparatus unit 1. In the first embodiment, the coating apparatus unit 1 is operated as a batch process, i.e., discontinuously. Other embodiments not shown here are expediently also operated as continuous coating processes for granules. The coating apparatus unit 1 has a coating apparatus 4 designed as a fluidization apparatus 2 in the form of a fluidized bed apparatus 3 for producing granules 6 functionally coated with a coating agent 5. In another embodiment, not shown, the coating apparatus 4 is designed as a spouted bed apparatus or as a drum coater.The fluidization apparatus 2, designed as a fluidized bed apparatus 3 in the first embodiment, has a fluidization chamber 8 designed as a coating chamber 7 and a process gas chamber 9 arranged below the fluidization chamber 8. The fluidization chamber 8 is separated from the process gas chamber 9 by a flow plate 10. Perforated floor plates, for example, are used as the flow plate 10. The granules 6 containing an active ingredient are produced in the fluidization chamber 8 or are fed in via a granulate inlet (not shown). The granules 6 are fluidized in a granulate bed 12 having a granulate bed height 11 by a process gas 13 flowing from the process gas chamber 9 into the fluidization chamber 8. The granulate bed height 11 depends on the volume flow or the flow velocity of the process gas 13 flowing into the fluidization chamber 8.After the coating process is complete, the coated granules 6 are discharged from the fluidization apparatus 2 via a granule discharge (also not shown). The process gas 13 is purified by means of a flushable filter 14 arranged in the fluidization apparatus 2 and, for example, fed back into the process gas chamber 9. Furthermore, a controllable spray device 15 and a process analysis tool 16 are arranged in the fluidization chamber 8, designed as a coating chamber 7. The process analysis tool 16 is designed as a measuring device 17 for the spectrally spatially resolved recording of the VIS-NIR absorption spectra, expediently as a VIS-NIR hyperspectral camera 18. A Hyperspec® EVNIR from HeadWall Photonics Inc., which had an NIR-corrected lens, was used as the VIS-NIR hyperspectral camera 18 in the tests.In this regard, the measuring device 17 is configured to detect VIS-NIR absorption spectra in a wavelength range between 250 nm and 2500 nm, expediently between 550 nm and 1700 nm. In the first embodiment shown, the active ingredient content is detected as an online measurement directly in the coating chamber 7. The spray device 15 has at least one spray element 19, wherein the spray element 19 is preferably designed as a multi-component nozzle 20. In the first embodiment, the spray device 15 is equipped with a spray element 19 designed as a multi-component nozzle 20 and is designed as a head spray unit 21. The coating agent 5 to be sprayed, in particular pH-dependent and pH-independent polymers, as well as an atomizing gas 22 having an atomizing gas pressure are supplied to the spray device 15.By adjusting the atomizer gas pressure, the droplet size of the droplets of coating agent 5 sprayed by the spray unit 15 can be adjusted. The droplet size of the droplets sprayed by the spray unit 15 can also be changed by adjusting the volume flow of the coating agent 5 to be sprayed. Furthermore, the coating apparatus unit 1 has a control device 23 connected to the spray device 15 and having a control functionality. The control device 23 is connected to the process analysis tool 16 via a data line 24. The process analysis tool 16 is configured to measure the active ingredient content of the granules and to transmit it to an evaluation unit 25 designed as a component of the control device 23.In the evaluation unit 25, the mass increase of the coating agent 5 applied to the granules 6 by means of the sprayed coating agent 5 can be determined, taking into account the measured active ingredient content of the granules 6, and thus also indirectly the layer thickness of the coating. The active ingredient content of the granules 6 measured by the process analysis tool 16 is transferred from the process analysis tool 16 to the control device 23 as the actual active ingredient content value. The control device 23, which has a control functionality, is configured to determine a control deviation between an active ingredient content target value and the active ingredient content measured as the actual active ingredient content value. The stored active ingredient content target value, which changes over time, is determined empirically, for example, through series of tests. In the control device 23, the determined control deviation is used to determine a manipulated variable, which is transmitted to the controllable spray device 15.To determine the manipulated variable, a function comprising a proportional element and an integral element is expediently used. The spray device 15 is controlled by the manipulated variable, in particular in such a way that an atomizer gas pressure of the spray device 15 or the spray rate of the spray device 15 can be or is controlled by the manipulated variable transmitted from the control device 23 to the spray device 15. It is also possible to adjust the amount of sprayed coating agent 5 in order to compensate for possible spray losses. Preferably, the control device 23 has an active ingredient content tolerance value and is configured to produce the granules 6 with an active ingredient content within the active ingredient content tolerance value. In the first embodiment, the atomizer gas pressure is controlled. This sets the droplet size of the droplets sprayed by the spray device 15 during the production of the granules 6. In Fig.Figure 2 shows a schematic representation of a second embodiment of a coating apparatus unit 1. In the second embodiment, identical components have the same reference numerals compared to the first embodiment. In contrast to the first embodiment, the fluidization apparatus 2 of the coating apparatus unit 1 has a spray device 15 designed as a bottom spray unit 26 and a vertically arranged riser pipe 27 centrally located in the coating chamber 7. Furthermore, the coating chamber 7 has a coating chamber bypass 28 in which the process analysis tool 16 is arranged. In the second embodiment, an online measurement of the active ingredient content takes place in the coating chamber bypass 28. The advantage of bottom spray coating (Wurster process) is a very uniform coating, coupled with optimal film quality.The coating process is therefore particularly suitable for the targeted functionalization of granules 6, especially for achieving defined and reproducible release profiles of an active ingredient. Bottom spray coating involves spraying from the bottom upwards. The spray elements 19, preferably the multi-component nozzles 20, are integrated into the flow plate 10 and are thus completely surrounded by the product. The combination of the flow plate 10 and the riser pipe 27 ensures targeted and controlled movement of the granules 6, which is a prerequisite for the optimal application of the coating agent 5 to the granules 6. The uniform residence times of the granules 6 in the spray zone 29 thus ensure a homogeneous film quality and application quantity to the individual granules 6. The granule speed in the riser pipe 27 also generates a high kinetic energy in the granule bed 12, which prevents the granules 6 from sticking together in a moist state.This allows even very small granules 6 to be coated without agglomeration. Since the bottom spray unit 26 is arranged in the middle of the granule flow and sprays evenly, premature evaporation of the carrier liquid is also prevented. The result is optimal film quality for the targeted functionalization of the granules 6. In a third embodiment (not shown but implemented), the spray device 15 was designed as a tangential spray unit. In a fourth and fifth embodiment (not illustrated), the measurement of the active ingredient content of the granules (6) is carried out as an at-line measurement or as an offline measurement. In a further embodiment, which has an at-line measurement of the active ingredient content of the granules (6), the evaluation unit (25) is designed as a stand-alone solution, so that the evaluation unit (25) can fulfill its function independently, i.e., without any additional devices.In a first experiment, granules 6 (MCC, Cellets® 200) were produced on the coating unit 1 shown in Fig. 2 (Glatt GPCG 1.1 with 6" riser tube 27 (Wurster insert)) using a cellulose-based binder and an anti-tacking agent with the aim of achieving an active ingredient loading of 50%, using a readily soluble active ingredient. In a second experiment, granules 6 were directly granulated on a coating unit 1 (not shown) using ProCell technology (ProCell 5), which enables the production of granules 6 with a high active ingredient content in a spray bed. The readily soluble active ingredient from the first experiment was used as the active ingredient. In the second experiment, two types of granules 6 were produced: granules 6 without a binder and thus with an active ingredient content of 100%, and granules 6 with 5% cellulose-based binder and an active ingredient content of 95%.All three granule populations were functionally coated with a mixture or a sequential coating of two pH-dependent polymers including release agent and plasticizer. When the single-thickness layer was applied as a coating with a mixture of two polymers, proportions of 10 to 60% or 30 to 60% were evaluated in 10% intervals; with sequential coating, only 30% coating proportions were investigated. A total of 16 samples were produced in this way, the properties of which are described in more detail in Table 1. The active ingredient content was measured using HPLC and DAD (PV 1741). Table 1 shows an overview of the 16 samples investigated, with the abbreviations W: Wurster, PC: ProCell, seq.: sequential coating, mix: mixture of polymers 1 and 2 applied, PEL: pellets:. The VIS-NIR hyperspectral data in the following experiments were acquired using a measuring device 17 (Hyperspec® EVNIR, HeadWall Photonics Inc., wavelength range: 560–1680 nm, spectral resolution 6 nm, spatial resolution 70 μm) in a push-broom configuration. It consists of an NIR line-scan camera with a lens, a spectrograph, a linear drive, and a halogen light source. To calculate the absorption of the samples, a Spectralon® standard with 99% reflection was measured. For each measured sample, the spatially resolved active ingredient content was calculated from the spatially resolved, preprocessed absorption spectra using PLS regression. The evaluation is performed using modeling with partial least squares regression. The 16 samples of the coated granules 6 examined were divided into a calibration and a test data set in a ratio of 1 / 1.Only the calibration dataset was used for the regression models. The test dataset was then used for validation. The regression models were evaluated using the following parameters: RMSEP: Root Mean Square Error of Prediction; Rank: Number of principal components included in the model; R. 2 (coefficient of determination): coefficient of determination RPD (residual prediction deviation): the ratio of the standard deviation of the prediction to the standard error of the validation The optimized calibration model provided the following properties after external validation: R 2= 99.82 RMSEP = 0.77 Rank = 5 RPD = 23.9 Figure 3 shows the scatter plot of the active ingredient contents calculated by the calibration model versus the active ingredient contents determined by HPLC and DAD (PV 1741) for the test data set. The actual active ingredient content of sample 4 was 81.35%, and the mean of the active ingredient content calculated by the calibration model used was 80.9%. For sample 12, the measured and predicted active ingredient contents were 29.33% and 30.5%, respectively. Due to the very good correlation between measured and predicted active ingredient contents, a measurement of the active ingredient content during a coating process is possible, regardless of the coating process performed.so that in the evaluation unit 25, taking into account the measured active ingredient content of the granules 6, the amount of coating agent 5 applied to the granules 6 can be determined, and thus the layer thickness of the layer applied to the granules 6 by means of the sprayed coating agent 5 can be determined at least indirectly. The method for producing granules 6 functionally coated with a coating agent 5, comprising a coating apparatus unit 1, with a coating apparatus 4 for coating the granules 6 with the coating agent 5, wherein the coating apparatus 4 has a coating chamber 7 and a spray device 15 arranged in the coating chamber 7 for spraying the coating agent 5,and wherein, in the coating chamber 7, the granules 6 containing an active ingredient are coated in a coating process by the spray device 15 with a quantity of coating agent 5 to form a layer having a layer thickness, and wherein the coating apparatus unit 1 has a process analysis tool 16 and an electronic evaluation unit 25. The process analysis tool 16 measures the active ingredient content of the granules 6, and this is transmitted to the evaluation unit 25, so that in the evaluation unit 25, taking into account the measured active ingredient content of the granules 6, the mass increase of the granules 6 is determined by means of the coating agent 5 applied to the granules 6. According to a preferred embodiment, the evaluation unit 25 determines a layer thickness of a layer of coating agent applied to the granules 6 from the mass increase of the granules 6.

Claims

Claims 1. Coating apparatus unit (1) for producing granules (6) functionally coated with a coating agent (5), comprising a coating apparatus (4) for coating the granules (6) with the coating agent (5), wherein the coating apparatus (4) has a coating chamber (7) and a spray device (15) arranged in the coating chamber (7) for spraying the coating agent (5), and wherein in the coating chamber (7) the granules (6) containing an active ingredient can be coated or are coated in a coating process by the spray device (15) with an amount of coating agent (5) to form a layer having a layer thickness, and wherein the coating apparatus unit (1) comprises a process analysis tool (16) and an electronic evaluation unit (25), characterized in that the process analysis tool (16) is suitable,to measure the active ingredient content of the granules (6), which is transmitted to the evaluation unit (25), so that in the evaluation unit (25) taking into account the measured active ingredient content of the granules (6), the mass increase of the granules (6) can be determined by means of the coating agent (5) applied to the granules (6).

2. Coating apparatus unit (1) according to claim 1, characterized in that the evaluation unit (25) is part of a control device (23) having a control functionality, which is configured to regulate and / or control the coating process taking into account the measured active ingredient content.

3. Coating apparatus unit (1) according to claim 2, characterized in that the control device (23) is further configured to determine a control deviation between a target active ingredient content value and the active ingredient content measured as the actual active ingredient content value, and to use the determined control deviation to determine a manipulated variable and to transmit this to the spray device (15). 4.Coating apparatus unit (1) according to claim 3, characterized in that the spraying device (15) is configured to be controllable or regulated by the control variable transmitted to the spraying device (15) by the control device (23).

5. Coating apparatus unit (1) according to claim 3 or 4, characterized in that the spraying device (15) is configured so that the atomizing gas pressure of the spraying device (15) or the spray rate of the spraying device (15) can be controlled or regulated by the control variable of the control device (23).

6. Coating apparatus unit (1) according to any one of the preceding claims, characterized in that the control device (23) has an active ingredient content tolerance value and is configured to produce the granules (6) with an active ingredient content within the active ingredient content tolerance value.

7. Coating apparatus unit (1) according to any one of the preceding claims, characterized in that the spray device (15) comprises at least one spray element (19).

8. Coating apparatus unit (1) according to claim 7, characterized in that the spray element (19) is configured as a multi-component nozzle (20).

9. Coating apparatus unit (1) according to any one of the preceding claims, characterized in that the spray device (15) is configured as a top (21) and / or bottom spray unit (26) and / or tangential spray unit.

10. Coating apparatus unit (1) according to any one of the preceding claims, characterized in that the coating apparatus (4) is configured as a drum coater or as a fluidization apparatus (2), wherein the fluidization apparatus (2) is expediently configured as a fluidized bed (3) or jet coating apparatus. 11.Coating apparatus unit (1) according to one of the preceding claims, characterized in that the process tool (16) is configured as a measuring device (17) for spatially resolved spectral acquisition of the VIS-NIR absorption spectra, expediently as a VIS-NIR hyperspectral camera (18).

12. Coating apparatus unit (1) according to claim 11, characterized in that the measuring device (17) is configured to acquire VIS-NIR absorption spectra in a wavelength range between 250 nm and 2700 nm, expediently between 550 nm and 1700 nm.

13. Coating apparatus unit (1) according to any one of the preceding claims, characterized in that the coating apparatus (4) comprises the process analysis tool (16), wherein the process analysis tool (16) is expediently arranged in the coating chamber (7) or a coating chamber bypass (28).

14. Coating apparatus unit (1) according to any one of the preceding claims, characterized in that the evaluation unit (25) is connected to the process tool (16), expediently via a data line (24).

15. Coating apparatus unit (1) according to any one of the preceding claims, characterized in that the evaluation unit (25) is configured to further determine, from the mass increase of the granules (6), a layer thickness of a layer of coating material (5) applied to the granules (6). 16.A method for producing granules (6) functionally coated with a coating agent (5), comprising a coating apparatus unit (1) with a coating apparatus (4) for coating the granules (6) with the coating agent (5), wherein the coating apparatus (4) comprises a coating chamber (7) and a spray device (15) arranged in the coating chamber (7) for spraying the coating agent (5), and wherein in the coating chamber (7) the granules (6) containing an active ingredient are coated in a coating process by the spray device (15) with an amount of coating agent (5) to form a layer having a layer thickness, and wherein the coating apparatus unit (1) comprises a process analysis tool (16) and a.

17. Method according to claim 16, characterized in that the process analysis tool (16) measures the active ingredient content of the granules (6) and transmits this to the evaluation unit (25), so that the mass increase of the granules (6) is determined in the evaluation unit (25) taking into account the measured active ingredient content of the granules (6) by means of the coating agent (5) applied to the granules (6).

18. Method according to claim 17, characterized in that the evaluation unit (25) is part of a control device (23) having a control function which regulates and / or controls the coating process taking into account the measured active ingredient content.

19. Method according to claim 17, characterized in that the control device (23) terminates the coating process when a desired active ingredient content of the granules (6) is reached.A method according to claim 17, characterized in that the control unit (23) regulates the coating process taking into account the measured active ingredient content by determining a control deviation between a target active ingredient content value and the actual active ingredient content measured as the actual active ingredient content value, and using the determined control deviation to determine a control variable and transmitting this variable to the spraying unit (15). A method according to claim 19, characterized in that the spraying unit (15) is configured to be controlled by the control variable transmitted from the control unit (23) to the spraying unit (15).

21. A method according to claim 19 or 20, characterized in that the spraying device (15) is configured such that the atomizing gas pressure of the spraying device (15) or the spraying rate of the spraying device (15) is controlled by the actuating variable of the control device (23).

22. A method according to any one of claims 16 to 21, characterized in that the control device (23) has an active ingredient content tolerance value and is configured to produce the granules (6) with an active ingredient content within the active ingredient content tolerance value.

23. Method according to one of claims 16 to 22, characterized in that the process tool (16) is designed as a measuring device (17) for spectrally spatially resolved acquisition of the VIS-NIR absorption spectra, expediently as a VIS-NIR hyperspectral camera (18), wherein VIS-NIR absorption spectra are acquired in a wavelength range between 250 nm and 2700 nm, expediently between 550 nm and 1700 nm.

24. Method according to one of claims 16 to 23, characterized in that the evaluation unit (25) further determines a layer thickness of a layer of coating agent (5) applied to the granules (6) from the mass increase of the granules (6).

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