JPH0613092B2 - Fluidized Granulation Coating Apparatus and Method - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to an apparatus and method for fluidized bed granulation and coating of powdery materials, and more particularly to an apparatus and method for producing coated granules of high quality, uniformity and good yield.

The present invention significantly improves the coating rate of spherical granules, and improves the sugar coating, coloring, enteric coating, fast dissolving, and
The present invention relates to a fluidized bed granulation and coating apparatus and method that can also be used for sustained-release and sustained-release coatings.

[Background technology]

It has long been known that granules obtained by fluid granulation of drug-containing powders or food raw material powders are formed by applying a necessary coating such as sugar coating or coloring under fluidization to form granules, and that a plurality of such granules are used to form pharmaceutical preparations or food products.

Recently, attention has been focused on formulation designs that use granules of an inert carrier such as sucrose, lactose, or corn starch (usually granules produced by fluidized bed granulation or tumbling granulation) as a core, the surface of which is coated with a drug-containing coating liquid, with the aim of achieving slow or sustained release of a drug (Japanese Patent Publication No. 45-33677, etc.).

For the preparation of such sustained-release or sustained-release preparations, it is advantageous to use a fluidized bed granulation/coating device that is capable of granulating or coating under fluidized conditions.

A typical example of this type of fluidized bed granulation and coating apparatus is the continuous type apparatus shown in FIG. 7, which is capable of not only granulation and coating in a solid-gas fluidized bed but also mixing and drying.

That is, the apparatus of FIG. 7 has a processing vessel 30, which is provided with a truncated cone-shaped portion 30a tapering downward, a bag filter 35, and a spray nozzle (spray gun) 37.
An air supply duct 31 is connected to the bottom of the processing vessel 30, and an exhaust duct 32 is connected to the top. An air flow straightening plate 33 made of a perforated plate is disposed between the processing vessel 30 and the air supply duct 31.
The processing vessel 30 is divided into a granulation and coating chamber 34 and a bag filter 35.
The bag filter 35 separates the granulation coating chamber 34 from the chamber 3 connected to the exhaust duct 32.
6 are defined. A spray nozzle 37 is provided in the granulation coating chamber 34 below the bubble filter 35, approximately in the center of the treatment vessel 30, and facing downward, and this spray nozzle 37 is adapted to spray, for example, a binder or a coating liquid into the granulation coating chamber 34. Air flows as shown by the dashed arrows in Fig. 7, causing the powder particles to rise and become fluidized in the fluidized coating chamber 34 (solid arrow). In this state, when a binder, for example, is sprayed from the nozzle 37,
After a predetermined time has passed and the product (granulated product, in this case granules) is produced, the exhaust port damper 38 is closed, and the granulated product flows out of the straightening plate 3.
The droplets fall and accumulate on the substrate 3. Reference numeral 39 denotes a heater, and reference numeral 40 denotes a filter.

In coating using this apparatus, the coating composition is dissolved in a solvent with a relatively high evaporation rate, and this is spray-coated onto the powder particles flowing in the granulation coating chamber 34 .

However, in the past, the spray nozzle 37 was installed inside the processing vessel 30 and sprayed downward during this granulation and coating process. As described above, the spray nozzle 37 is located above the granulation and coating chamber 34,
The binder or coating liquid is sprayed downward from above the granulation coating chamber 34. The spray nozzles are not always located in the upper center of the granulation coating chamber as described above, but may also be installed on the upper wall of the treatment vessel to spray diagonally downward. Another device has also been proposed in which the spray nozzles are installed at the bottom of the treatment vessel or below the air inlet in the air inlet duct to spray upward (Fluidized Bed Granulation and Coating Apparatus; Chemical Factory, Vol. 24, No. 5, pp. 51-59 (1980)).
), Japanese Patent Publication No. 59-73042, etc.].

Furthermore, Japanese Patent Publication No. 54-44268 discloses a funnel-shaped device consisting of an inverted cone section with a cylindrical body and a perforated plate at the bottom, and legs that serve as gas ejection pipes, in which a coating agent supply pipe is protruded upward close to the ejection port of the gas ejection pipe to supply the coating agent to the ejection section.

In addition, as a related art, Japanese Utility Model Publication No. 51-14914 states:
The apparatus shown has a spray device attached to the outer wall of the fluidized bed body, and its mounting angle _θ1 , based on the center line, can be changed in the range of 0 to 60°, and _θ2 , based on the vertical axis, can be changed in the range of 0 to 150°. This spray device can also be used to supply spray liquid from obliquely below to obliquely above.

[Technical issues]

In techniques where a spray nozzle is installed above the interior space of the treatment vessel or on the upper vessel wall of the treatment vessel and sprays downward or obliquely downward, the fluidized powder or spray liquid adheres to the spray nozzle, changing the spray pattern. Furthermore, the spray droplets dry out due to the fluidizing air, adhere to the powder, and scatter before being coated. Furthermore, the low probability of contact between the spray droplets and the powder leads to problems such as scattering and scattering. Furthermore, even if a spray nozzle spraying downward from above is immersed in the flowing powder, the same problems occur. Furthermore, in the above-mentioned techniques, when the material to be coated is spherical granules, the weight of the spherical granules themselves prevents sufficient fluidization within the treatment vessel, unlike powder granules. As a result, the fluidized granules concentrate below the middle of the treatment vessel, resulting in a high density in that area, especially in the peripheral wall of the truncated cone tapering downward. In order to move the fluidized bed upward, it is conceivable to increase the inflow air pressure and air volume. However, as mentioned above, increasing the inflow air pressure and air volume results in the coating liquid scattering, distorting the spray pattern, and making it difficult to obtain a stable coating. Thus, when coating spherical granules with conventional techniques that use a nozzle (spray nozzle) installed above the processing vessel, the gap between the nozzle and the spherical granules is too large, resulting in the spray liquid drying out and becoming fine powder before adhering to the spherical granules, which then dissipates. Furthermore, unlike powders, spherical granules have a certain surface area. Therefore, if the fluidization is insufficient, problems such as partial coating or insufficient stable coating occur.

In addition, a spray nozzle is installed at the bottom of the treatment vessel or below the air inlet, and sprays upward.
In the technique described in No. 268, in which the coating agent supply pipe is extended to the jet portion to spray the coating agent,
Because the temperature of the fluidized airflow is high due to the coating,
This accelerates the drying and scattering of the spray liquid, and also causes the blow-through phenomenon due to the spray air flow, which leads to the drying and scattering of the spray liquid. This also narrows the control range of the spray air volume, making it easier for the powder to aggregate and form agglomerates. Furthermore, if the spray nozzle is positioned at the bottom, the powder will adhere to the spray nozzle, changing the spray pattern and making it difficult to achieve a stable coating.

The technology disclosed in Japanese Utility Model Publication No. 51-14914 aims to control the spray angle within a certain range in a conventional device in which a spray device is attached to the vertical portion of the outer wall of a cylindrical portion. Therefore, this device has the problems of the technology of spraying from obliquely above to obliquely below, and
In a fluidization tank that does not have a downwardly tapered truncated cone portion, a uniform flow of powder particles is not formed, resulting in a lack of coating stability and an increased likelihood of agglomeration.

Furthermore, the technology of JP-A-59-73041 is consistent with the description of JP-B-54-44268 in that the spray liquid is supplied directly to the jet section, but the technology of JP-B-54-44268 has the problems of the spray liquid drying and scattering, the blow-through phenomenon, and the generation of agglomerates.

As described above, all of these prior art techniques have problems such as scattering and dispersal of the binder or sprayed coating liquid due to fluidizing air, and lack coating stability.
In particular, in the case of spherical granules, it is not possible to produce high-quality, uniform coated granules even if the coating process is carried out over a long period of time. Furthermore, these conventional techniques tend to produce agglomerates, which significantly affect yield and quality, resulting in significant economic losses.

In particular, it has been extremely difficult to achieve the objective of producing sustained-release and sustained-release preparations, which require high quality and homogeneity, using these conventional techniques.

As a related technique, a so-called centrifugal fluidized bed granulation coating apparatus equipped with an aerated rotating plate in a processing vessel is known.
A technology has been disclosed in which a tapered truncated conical section and a vertical cylindrical section are provided, and the spray liquid is supplied from the vertical cylindrical section. However, this device is a fluidized bed granulation/coating device that involves the rotation of a rotor, and its function is completely different. Moreover, since the nozzle is provided in the vertical section where the flow of powder and granules is not uniform, the same problems as in Japanese Utility Model Publication No. 51-14914 arise. Furthermore, in normal use, the problems of drying and scattering of the spray liquid, a decrease in the coating rate, and the generation of agglomerates cannot be traced back to the fluidizing air flow from the slit section (this problem is also addressed in Japanese Patent Publication No. 57-171429, Japanese Utility Model Publication No. 59-180725, and Pharm.Indust., 41 (1
0), 973-976 (1979), a problem common to the art.

These problems were mainly caused by the correlation between the flow conditions of the powder and granules and the properties and supply conditions of the coating liquid and binder, and were recognized to be particularly evident when coating spherical granules, but could not be solved by simply improving these factors.

DISCLOSURE OF THE INVENTION

SUMMARY OF THE INVENTION An object of the present invention is to provide a fluidized bed granulation and coating apparatus and method which can solve the above problems and enable stable coating even on spherical granules.

In order to solve the above technical problems, the present invention employs the following technical means. That is, to explain based on the embodiment shown in the drawings, in Fig. 1, the attachment position of the spray nozzle 4 is provided in a truncated cone portion 2 tapering downward, below the interface of the flowing powder or granules (particularly spherical granules) indicated by the solid arrow. Here, the truncated cone portion tapering downward is the truncated cone portion A shown in Fig. 1 illustrating the embodiment.
The wall is not necessarily limited to a truncated cone wall, and any wall configuration is acceptable as long as it allows uniformly flowing powder particles to be sprayed directly onto the high-density area.

Furthermore, as shown in Figure 2, a spray nozzle 4 is provided in the truncated cone portion 2 of the treatment vessel 1 below the interface of the flowing powder or granules (particularly spherical granules) as in Figure 1, and a compressed air ejection nozzle 15 is also provided in the truncated cone portion (position A) below the interface of the flowing powder or granules (particularly spherical granules).

As shown in Figures 3 and 4, a spray nozzle 4, similar to that shown in Figure 1, may be provided in the truncated conical portion 2 below the interface of the flowing powder or granules (particularly spherical granules); or, similar to that shown in Figure 2, a compressed air jet nozzle 15 may be provided in the truncated conical portion 2 below the interface of the flowing powder or granules (particularly spherical granules), in addition to the configuration shown in Figure 1, and if desired, a temperature measuring element may be provided in: (1) a compressed air pipe line connected to the spray nozzle 4 upstream of the fluidized bed granulation and coating apparatus, (2) in the flowing powder or granules, and/or (3) when a compressed air jet nozzle is used, in a pipe line connected to the compressed air jet nozzle upstream of the fluidized bed granulation and coating apparatus.

[Effect]

All conventional fluidized bed granulation and coating equipment have in common the fact that they spray coating liquid and binder directly onto the part of the flowing powder where the concentration is low, i.e., onto the layer where the powder is packed at a low density. This is recognized to be the main cause of the significant reduction in the coating rate, especially for spherical granules.

In this type of fluidized bed granulation/coating apparatus, as is clear from the flow pattern, the powder and granule concentration is low in the jet section where the fluidizing airflow speed is high and at the interface of the flowing powder and granules, and the powder and granules form a high-density layer, i.e., a high-packing density layer, in the section where the fluidizing airflow speed is low and the powder and granules drop. Therefore, in a fluidized bed granulation/coating apparatus having a cylindrical treatment vessel with a truncated conical lower section tapering downward, as shown in Figure 7, the peripheral wall of the truncated conical section not only achieves uniform powder and granule flow due to its shape, but also forms an area where the powder and granules and agglomerates have a high density because the fluidizing airflow speed is low.

Contrary to the prior art, the present invention involves spraying a coating liquid or binder directly onto the densest part of uniformly flowing powder particles to granulate and coat them.

According to the present invention having such a configuration, the coating rate of granules, particularly spherical granules, can be improved significantly, and a fluidized bed granulation and coating apparatus that can also be used to coat spherical granules can be provided.

That is, in the present invention, a coating liquid or binder is sprayed directly onto uniformly flowing powder or granules, particularly near the high density of spherical granules, so that the probability of contact between the sprayed droplets and the powder or granules is greatly increased, and the sprayed liquid is not dried and scattered away by the fluidizing air flow. As a result, efficient granulation or coating can be achieved in a short time, and uneven coating is eliminated, resulting in an improved yield.

In addition, since the spray nozzle is located in the truncated cone part of the processing vessel, it is cleaned by the powder circulating inside the processing vessel, so the spray pattern does not change and stable granulation and coating is possible.Furthermore, since it is not located at the bottom, there is no adhesion or contamination of the spray nozzle.

Furthermore, since the effects of air pressure, air volume, temperature, etc., as in the past, are less pronounced, the control conditions can be broadened, making handling easier, and it is possible to suppress the occurrence of agglomeration by increasing air pressure and air volume. Furthermore, as a secondary effect of the spray air from the spray nozzle, agglomerates of powder and granules are appropriately broken down, allowing for optional adjustment of particle size. This allows for coating without the need for sorting the granules after granulation. Furthermore, by controlling the amount of spray air, air pressure, etc. from the compressed air ejection nozzle, it is possible to prevent the agglomeration and agglomeration of powder and granules.

[Brief explanation of the drawings]

FIG. 1 is a schematic cross-sectional view showing the configuration of one embodiment of the present invention, FIG. 2 is a schematic cross-sectional view showing the configuration of another embodiment of the present invention, FIG. 3 is a schematic cross-sectional view showing the configuration of yet another embodiment of the present invention, FIG. 4 is a schematic cross-sectional view showing the configuration of yet another embodiment of the present invention, FIG. 5 is a schematic cross-sectional view showing the configuration of yet another embodiment of the present invention, FIG. 6 is a schematic cross-sectional view showing the configuration of yet another embodiment of the present invention, and FIG. 7 is a schematic cross-sectional view showing the configuration of a conventional fluidized granulation/coating apparatus. In the drawings, reference numeral 1 denotes a fluidized bed granulation/coating apparatus, 2 denotes a truncated cone portion, 3 and 12 denote filters, 4 denotes a spray nozzle, 5 denotes an air supply duct, 6 denotes an exhaust duct, 8 denotes a granulation/coating chamber, 9 and 16 denote pipelines, 13 denotes a heater, 15 denotes a compressed air nozzle, 17 denotes an air humidity control device, 18 denotes a heater (cooler), 19 and 20 denote temperature measuring elements, 21 denotes a compressed air heater (cooler), 22 denotes a dehumidifier (cooler), 23 denotes a compressor, 24 and 25 denote signal generators, 26 denotes a temperature detection control device, 27 denotes a granulation/coating control device, and 28 denotes pipelines. [Best Mode for Carrying Out the Invention] Hereinafter, embodiments of the present invention will be described with reference to the drawings. However, it should be understood that the components and other parts and their arrangements described or illustrated in the following examples are not intended to limit the scope of the present invention and are merely illustrative. Figure 1 is a cross-sectional view showing the configuration of one embodiment of the present invention. In this example, the coating of spherical granules will be described, but the invention is not limited to coating and can be applied to granulation. In the figure, a processing vessel 1 is equipped with a truncated cone part 2, a bag filter 3, a spray nozzle 4, etc. An air supply duct 5 is connected to the bottom of the processing vessel 1, and the processing vessel 1
An exhaust duct 6 is connected to the top of the treatment vessel 1. An air flow straightening plate 7 made of a perforated plate is disposed between the treatment vessel 1 and the air supply duct 5, and this air flow straightening plate 7 separates the air supply duct 5 from the granulation coating chamber 8. A bag filter 3 is disposed at the top inside the treatment vessel 1, and this bag filter 3 separates the granulation coating chamber 8 from a chamber 10 connected to the exhaust duct 6. A spray nozzle 4 is provided in the granulation coating chamber 8 at the position of the truncated cone portion 2, below the interface of the flowing spherical granules. This spray nozzle 4
Atomizing air and coating liquid, for example, are supplied to the nozzle 4 via a conduit 9 and a metering pump (not shown), and the coating liquid is sprayed into the granulation coating chamber 8. In this example, the nozzle 4 is oriented upward relative to the horizontal with respect to the processing vessel 1. However, the orientation of the nozzle 4 in this example is not limiting to the present invention, and it may be oriented downward. Furthermore, the spray direction may be controlled by arbitrarily changing the orientation up, down, left, or right. In a fluidized bed granulation and coating apparatus configured as described above, for coating, spherical granules, for example, are introduced into the processing vessel 1 through a material supply port (not shown) and then closed. Spherical or irregularly shaped granules used as the core of sustained-release or sustained-release formulations are typically composed of 100 to 20% by weight of a single or mixture of inert carriers, such as sucrose, lactose, corn starch, and crystalline cellulose. Further components mixed with the carriers include substances that adjust the disintegration and solubility of the granules, such as calcium carboxymethylcellulose, sodium carboxymethylcellulose, D-mannitol, and other starches. Next, when the exhaust fan (not shown) is operated, air flows as shown by the dashed arrow in Fig. 1, causing the spherical granules to fly up and become fluidized in the granulation coating chamber 8. When the coating liquid is sprayed from the nozzle 4 in this state, the coating liquid, for example, obtained by dissolving the coating liquid in a solvent with a relatively high evaporation rate, is sprayed from the spray nozzle 4 toward the high-density part of the spherical granules flowing homogeneously in the spray coating chamber 8. As the drug-containing coating liquid for sustained-release or sustained-release preparations, drugs for which sustained-release or sustained-release preparations are needed, for example, various circulatory system drugs such as dipyridamole and various antibiotics, are coated with propylene glycol, polyethylene glycol (macrogol), polyvinylpyrrolidone (P
VP), polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), methylcellulose (M
The coating agent may be dissolved in alcohols such as ethanol, organic solvents such as methylene chloride, water, or a mixture thereof, together with methacrylic acid/methacrylic acid ester copolymers, pregelatinized starch, dextrin, polysorbate 80, sorbitan mono-fatty acid esters, sucrose fatty acid esters, polyoxyl 40 stearate, etc., or in water or a mixture thereof. After a predetermined time has elapsed, coated spherical granules are produced. When the exhaust damper 11 is closed, the coated spherical granules fall and accumulate on the straightening plate 7. An outlet is provided on the side wall at the bottom of the granulation coating chamber 8, and an on-off valve for opening and closing the outlet is attached to the outlet (neither is shown). The end of the air intake duct 5 is open to the atmosphere, and a filter 12 for filtering and purifying the intake air and a heater 13 for heating the air are installed along the duct. The end of the exhaust duct 6 is connected to an exhaust fan (not shown).
An exhaust port damper 11 is disposed at the connecting port between the exhaust duct 12 and the chamber 10 to open and close this connecting port.
The exhaust port of the exhaust fan is connected to a dust collector (not shown). In the above embodiment, one spray nozzle is provided at a predetermined position on the downwardly tapered truncated cone portion provided at the bottom of the treatment vessel, but the number of nozzles is not limited to one and multiple nozzles can be provided.
Preferably, 2 to 8 nozzles are provided at equal intervals. By providing a plurality of nozzles in this manner, the spray pattern can be made more stable. For example, using a device having the above-described configuration, air heated to a predetermined temperature is supplied from an air supply duct 5 into a cylindrical treatment vessel 1 having a truncated cone portion 2 tapering downward, and at the same time, this supplied air is discharged from an exhaust duct 6 via a filter 3. In this manner, the powder or spherical granules in the treatment vessel 1 are made to flow. Then, the binder or coating liquid is applied to a predetermined portion of the truncated cone portion tapering downward provided at the bottom of the treatment vessel 1 toward the vicinity of the high density of the powder or spherical granules that are flowing uniformly (see FIG. 1A).
This results in a fluidized bed granulation and coating method in which the fluidized bed is discharged from a fluidizing air source (range A) and granulated from powder or granules or coated onto spherical granules. The fluidization conditions, such as fluidizing air pressure, fluidizing air volume, temperature, and time, the granulation and coating conditions, such as the supply amount, supply pressure, temperature, and time of the binder and coating liquid, and the mixing and drying conditions, are controlled automatically by a control panel that systematically controls the entire apparatus. Next, the invention shown in the embodiment in Figure 2 will be described. Figure 2 is a cross-sectional view showing the configuration of another embodiment of the invention. In this description, the same members and components as those shown in Figure 1 are designated by the same reference numerals and will not be described again. In this example, as in the example described in Figure 1, the spray nozzle 4 is attached so that the truncated cone portion 2 is positioned below the interface of the flowing powder or granules (range A in the drawing). In this example, the nozzle 4 is oriented upward relative to the horizontal with respect to the processing vessel 1, but this is not limiting. According to this embodiment, a compressed air jet nozzle 15 is further provided in the truncated cone portion (range A in the drawing) below the interface of the flowing powder or granules or spherical granules. In this embodiment, the compressed air jet nozzle is also provided facing upward from the horizontal with respect to the processing vessel 1, but this is not limited to this. For example, the compressed air nozzle 15 is provided on the vessel wall of the processing vessel 1 below the interface of the flowing powder or granules, and sprays upward or downward. The direction may also be changed arbitrarily. The number of compressed air nozzles 15 is preferably in the range of 1 to 8, but is not limited to this. The number of compressed air nozzles 15 may or may not match the number of spray nozzles 4. Nozzles 15
The direction of the compressed air may be the same, but preferably, the compressed air is blown from different directions toward the center of the truncated cone portion 2 provided in the treatment vessel 1, thereby ensuring the flow of the powder or spherical granules. The flow velocity of the compressed air may be within a range that can suppress and control the generation of agglomerates of the powder or spherical granules, and this range is generally 50 to 1000 m/s, and preferably 100 to 600 m/s. By appropriately adjusting the flow velocity of the compressed air in this way,
This prevents excessive grinding and the formation of agglomerates, allowing for efficient granulation and coating. Furthermore, since the flow rate of compressed air can be adjusted during granulation using this apparatus, the resulting grinding effect can be utilized to freely adjust the particle size of the granules. Therefore, granules can be coated without sorting after granulation. The compressed air nozzle is connected to a heater, compressed air generator, control device, etc. (all not shown) via a pipe 16, and the desired flow rate, temperature, humidity, time, and other conditions are automatically controlled by a computer or other device in response to the operation of the entire apparatus. For example, using the apparatus configured as described above, air heated to a predetermined temperature is supplied through the air supply duct 5 into the cylindrical processing vessel 1 having the truncated cone portion 2, and simultaneously, the supplied air is exhausted through the exhaust duct 6 via the filter 3, as in the embodiment of the method invention described above. In this manner, the powder or spherical granules in the processing vessel 1 are fluidized. At the same time, compressed air is exhausted from a predetermined location in the truncated cone portion 2 of the processing vessel 1. Then, a binder or coating liquid is sprayed from a predetermined location (range A in Figure 2) of a downwardly tapering truncated cone-shaped portion provided at the bottom of the treatment vessel 1 toward the vicinity of the high density of the uniformly flowing powder or spherical granules, thereby granulating the powder or coating the granules (especially the spherical granules). The flow rate of the compressed air and other conditions are the same as those described above. In the above explanations, detailed explanations of the operation and control methods of the dampers, etc. have been omitted, but these are automatic on-off valves operated, for example, by electricity or air pressure, and
The entire apparatus is automatically controlled by a control panel which systematically controls the apparatus. Next, Fig. 3 is a cross-sectional view showing the configuration of one embodiment of the present invention, in which the same members and configurations as those shown in Fig. 1 are given the same reference numerals and their explanation will be omitted. In this embodiment, as in the example explained in Fig. 1, the spray nozzle 4 is attached to the truncated conical portion 2 below the interface of the flowing powder and granules, particularly spherical granules.
The spray nozzle 4 is supplied with a binder or coating liquid via a pipe 9 and a metering pump (not shown). On the other hand, the other pipe 28 connected to the spray nozzle 4 is connected to a heater (or cooler) 2 for compressed air.
1, compressed air dehumidifier (cooler) 22, compressor 2
The compressed air is sent to the dehumidifier 22 to remove moisture from the compressed air. In the dehumidifier 22, the compressed air is cooled to about -10°C and dehumidified. The cooled and dehumidified compressed air is sent to the next heater (or cooler) 2
At this time, the portion of the pipe 28 before the processing vessel 1 (preferably, the portion before the processing vessel 1) is heated (or cooled) by the
An electrical temperature measuring element 19, for example, is arranged in the area closest to the treatment vessel 1, which is not affected by the temperature of the treatment vessel itself.
Meanwhile, in the granulation/coating chamber 8 of the processing vessel 1, an electrical temperature measuring element 20, for example, is disposed at a location where the powder or granules are fluidized, preferably near the high density of the fluidized powder or granules. The former measuring element 20 is connected to a signal generator 24, which generates a signal corresponding to the measured temperature. The signal generated by the signal generator 24 is read by a subsequent detection controller 26, which then detects the temperature.
Furthermore, the fluidized bed granulation/coating control device 27, which controls the entire apparatus, controls the compressed air heater (cooler) 21 to maintain the temperature of the compressed air at a predetermined temperature. The latter element 20 is connected to another signal generator 25, and is further read by the temperature detection control device 26, which controls the entire apparatus. While one element of temperature control is sufficient, it is preferable to control the temperature based on both elements. That is, the information obtained from the temperature measurement of the element 20 provided in the granulation/coating chamber 8 and the information obtained from the temperature measuring element 19 provided in the pipeline 28 are used to control the compressed air heater 21 and the heater 18 for heating the air via the control device 27, so that they are each maintained at a predetermined temperature. In this example, the heater 18 is controlled by the heater 1.
The amount of steam flowing into the spray nozzle 8 is controlled by adjusting a valve, but an electric heater or other heating element may be used instead of steam. The spray liquid is then sprayed from the spray nozzle 4 using compressed air under the most appropriate conditions, while the fluidizing air flow is also appropriately controlled. In the above description, heaters 18 and 21 have been described as heaters, but depending on the summer season and the characteristics of the spray liquid, they may need to be used as coolers to maintain the desired temperature. For this reason, heaters 18 and 21 are preferably designed to function as coolers, but they may also be connected separately and used selectively. Therefore, the temperature control range generally varies depending on the characteristics of the material and the spray liquid, but it is sufficient to be adaptable to a range of 0 to 100°C. Next, Figure 4 shows an apparatus that combines the apparatus of Figure 2 with the temperature control method of Figure 3. In this example, a temperature measuring element 19 is also installed in the pipe 16 connected to the compressed air nozzle to control the temperature of the compressed air for more reliable temperature control, but this is not necessarily required. Next, another invention will be described. This invention is configured so that the spray nozzle may be provided above the center of the treatment vessel as in the prior art, on the upper vessel wall of the treatment vessel, or on the bottom of the treatment vessel or below the air flow straightening plate as explained in the above inventions. That is, the gist of this invention is a fluidized bed granulation/coating apparatus having at least one spray nozzle, a cylindrical treatment vessel equipped with at least an air inlet duct, an air outlet duct, and a truncated conical portion tapering downward,
This relates to a fluidized bed granulation and coating apparatus characterized in that a compressed air jet nozzle is provided in the truncated cone portion below the interface of the flowing powder or granules. Figs. 5 and 6 showing an embodiment of this invention will be explained with reference to the symbols in Figs. 2, 4 and 7. The compressed air jet nozzle 15 is provided in a truncated cone portion (range A in the drawing) below the interface of the flowing powder or granules. In this example, the compressed air jet nozzle is also provided facing upward from horizontal 5 relative to the processing vessel 1, but this is not limiting. For example, the compressed air nozzle 15 is provided on the vessel wall of the processing vessel 1 below the interface of the flowing powder or granules. The number of compressed air nozzles 15 can be 1 to 8.
The range is preferred, but not limited to this.
Furthermore, by arranging the nozzles 15 at equal intervals, the fluidization of the powder or spherical granules can be made uniform, but even if the intervals are not equal, this can be adjusted by adjusting the predetermined air pressure and air volume. The direction of the nozzles 15 may be in one direction, but preferably, compressed air is blown from different directions toward the center of the truncated cone portion 2 provided in the treatment vessel 1, thereby ensuring the flow of the powder or spherical granules. The flow rate of this compressed air may be within a range that can suppress and control the generation of agglomerates of the powder or spherical granules, and this range is generally 50 to 1000 m/s, preferably 100 to 600 m/s. By appropriately adjusting the flow rate of the compressed air in this way,
This prevents excessive crushing and the occurrence of agglomerates, allowing for efficient granulation and coating. Furthermore, when granulating with this device, the flow rate of compressed air can be adjusted, and the resulting crushing effect can be utilized to adjust the particle size of the granules as desired. Therefore, the granules can be subjected to coating without being sorted after granulation. As is clear from Figure 6, the compressed air nozzle is connected to a heater or cooler 21 via a pipe 16, and to a compressor 22 after generating the compressed air.
2, a control device 27, etc., and is controlled so that compressed air having the desired flow rate, temperature, humidity, etc. is ejected from the nozzle 15 in response to the operation of the entire apparatus. By configuring as described above, it is possible to advantageously prevent the aggregation and agglomeration of powder and granules by controlling, for example, the amount of spray air, air pressure, and temperature of the compressed air ejection nozzle, regardless of the position of the spray nozzle. [Effects of the Invention] The present invention, configured as described above, has the following advantages: It enables efficient coating of powder and granules in a short time without drying out and dissipating the spray droplets. It significantly increases the coating rate of spherical granules in particular, enabling the production of high-quality, uniform, and highly productive coated spherical granules. This enables drug coating of the core of an inactive carrier for sustained-release and sustained-release formulations. It prevents the formation of agglomerates during granulation and coating. There is absolutely no adhesion or contamination to the spray nozzle nozzle. Since particle size is not a factor in granulation, particle size can be freely adjusted. This eliminates the need for particle sorting after granulation. In particular, the coating rate of spherical granules and the effect on the occurrence of agglomeration were confirmed by the following experimental examples. Experimental Example 1: 8,000 g of spherical granules having a size of 32 to 42 mesh (495 to 350 μm) were charged into the apparatus shown in Figure 4 and kept in a fluidized state under conditions of a fluidizing air volume of 6 to ⁹ m3/min and a powder temperature of 50°C. 9 parts of an active substance, 9 parts of a methacrylic acid-methyl methacrylate copolymer, polysorbate 80,
A coating solution prepared by dissolving 2 parts of ethanol in 80 parts of a methanol-methylene chloride mixed solvent was sprayed at a spray air pressure of 3 to 4.5 kg/cm ² , a spray air rate of 250 to 300/min, and a spray air temperature of 40 to
50°C, coating liquid supply rate 100-200g/min
35,000 g of the coating liquid was sprayed and supplied under the conditions of 15.
Air was sprayed at a flow rate of 0 m/sec. As a result, the adhesion rate of the coating liquid composition to the spherical granules, i.e., the coating rate, was 97%, and it was homogeneous. The rate of agglomeration (the rate of granules that passed through a 24 mesh sieve when sieved) was 2%. In addition, the rate of agglomeration when air was not sprayed from the compressed air spray nozzle was 5%.
As a conventional general method, the same amount of spherical granules as described above were charged into the apparatus shown in Figure 7, and the fluidized state was maintained under the same conditions as described above. 35,000 g of the above coating liquid was sprayed onto the granules at an air pressure of 3 to 45 kg/ ^cm2 , an air flow rate of 250 to 300/min, and a spraying speed of 1000 kJ/min.
The coating solution was sprayed at a supply rate of 100-200 g/min to coat the spherical granules. The spray nozzle was immersed in the fluidized spherical granules to ensure good coating. The coating rate with the conventional device was 85%, and the rate of clumping was 11%. Experimental Example 2: 8,000 g of spherical granules with a size of 32-42 mesh (495-350 μm) were charged into the device shown in Figure 4, and fluidized at a fluidizing air volume of 6-9 ^m3 /min and a powder temperature of 40°C. 6 parts of the active substance, 8 parts of hydroxypropylmethylcellulose, Macrogol 400, and 6 parts of hydroxypropylmethylcellulose were added.
50,000 g of a coating solution prepared by dissolving 1 part of 00 in 85 parts of a methanol-methylene chloride mixed solvent was sprayed at an air pressure of 3
up to 4.5 kg/ ^cm2 , spray air volume 250-300/min,
Spray air temperature 30 to 45°C, coating liquid supply amount 10
The coating was carried out by spraying the material at a rate of 0 to 350 g/min. The compressed air was sprayed from a nozzle at a rate of 150 m/sec.
The air was sprayed at a flow rate of 1000 rpm. As a result, the coating rate was 99% and the coating was homogeneous. The rate of agglomeration was 2%. When air was not sprayed from the compressed air nozzle, the rate of agglomeration was 4%.
As a conventional general method, the same amount of spherical granules as described above was charged into the apparatus shown in Figure 7, and the fluidized state was maintained under the same conditions as described above. 50,000 g of the coating liquid was sprayed onto the granules at an air pressure of 3 to 4.5 kg/ ^cm² and an air volume of 250 to 300 g.
The coating was carried out by spraying and supplying the coating liquid under the conditions of a fluidizing air flow rate of 6-9 m3/min and a coating liquid supply rate of 100-350 g/min. At this time, the spray gun was immersed in the spherical granules in a fluidized state. As a result, with the conventional device, the coating rate was 80% and the rate of agglomeration was 9%. Experimental Example 3 15,000 g of spherical granules containing an active substance with a size of 24-42 mesh (700-350 μm) were charged into the device shown in Figure 4, and the fluidizing air flow rate was 6-9 ^m3 /min, the powder temperature was 3
The mixture was kept in a fluidized state at 0 ° C., and 5,000 g of a coating solution prepared by dissolving 9 parts of a polymer of ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate chloride and 1 part of Macrogol 400 in 90 parts of a methanol-methylene chloride mixed solvent was sprayed and supplied under the following conditions: spray air pressure 3 kg/cm ² , spray air volume 250/min, spray air temperature 5 ° C., and coating solution supply volume 100 g/min. At this time, air was sprayed at a flow rate of 150 m/sec using a compressed air spray nozzle. As a result, the coating rate was 96%, and the aggregated particle generation rate (the percentage of particles that passed through a 20-mesh sieve when sieved) was 1%. The spherical granule surfaces were coated smoothly and uniformly. When air was not sprayed from the compressed air spray nozzle, the aggregated particle generation rate was 3%. As a conventional general method, the same amount of spherical granules as described above were charged into the device shown in Figure 7 and kept in a fluidized state under the same conditions as above, and 5,000 g of the above coating liquid was sprayed and supplied under the conditions of an atomizing air pressure of 3 kg/ ^cm2 , an atomizing air volume of 250/min, and a coating liquid supply volume of 100 g/min to coat them. At this time, the spray gun was immersed in the spherical granules in a fluidized state. As a result, the coating rate with the conventional device was 75%, and the rate of agglomeration was 6%. The spherical granules had many irregularities on their surfaces,
It was unevenly coated.

Claims (12)

[Claims] [Claim 1] A fluidized bed granulation and coating apparatus having a cylindrical processing vessel equipped with at least one spray nozzle, at least an air intake duct, an air exhaust duct, and a truncated cone portion tapering downward, characterized in that: (a) the spray nozzle is attached to the truncated cone portion below the interface of the flowing powder or granular material; (b) the compressed air supplied to the spray nozzle and/or the air flow for fluidizing the powder or granular material is temperature-controlled based on the temperature measurement results of the air flow in the pipe supplying the compressed air and/or the temperature measurement results of the powder or granular material being fluidized; and (c) an air flow straightening plate consisting of a perforated plate is disposed in the lower part of the processing vessel. 2. The fluidized bed granulation and coating apparatus according to claim 1, wherein the powder particles are spherical granules. 3. The fluidized bed granulation and coating apparatus according to claim 1 or 2, wherein the coating is a coating liquid containing a pharmaceutical agent. [Claim 4] A fluidized bed granulation and coating apparatus having a cylindrical processing vessel equipped with at least one spray nozzle, at least an air intake duct and an exhaust duct, and a truncated conical section tapering downward, characterized in that: (a) the spray nozzle is attached to said truncated conical section below the interface of the flowing powder or granule; (b) a compressed air jet nozzle is attached to said truncated conical section below the interface of the flowing powder or granule; (c) the compressed air supplied to said spray nozzle and/or said compressed air jet nozzle, and/or the air flow for fluidizing said powder or granule, is temperature-controlled based on the temperature measurement results of the air flow in the pipe supplying the compressed air and/or the temperature measurement results of the powder or granule to be fluidized; and (d) an air flow straightening plate consisting of a perforated plate is disposed in the lower part of said processing vessel. 5. The fluidized bed granulation and coating apparatus according to claim 4, wherein said powder and granules are spherical granules. 6. The fluidized bed granulation and coating apparatus according to claim 4 or 5, wherein the coating is a coating liquid containing a pharmaceutical agent. [Claim 7] A method for fluidized granulation and coating, characterized in that air is supplied from an air supply duct into a cylindrical processing vessel having a truncated conical section tapering downward, and simultaneously the supplied air is discharged from an exhaust duct to fluidize the powder or granules in the processing vessel, and a binder or coating liquid is sprayed from the truncated conical section below the interface of the flowing powder or granules near the inner wall of the truncated conical section where the flowing powder or granules have a high density, thereby granulating or coating the powder or granules, and the granulation or coating is carried out while controlling the temperature of compressed air supplied to a spray nozzle and/or the air stream fluidizing the powder or granules based on temperature measurements of the air stream in a pipeline supplying compressed air and/or the temperature of the powder or granules to be fluidized, and the air stream fluidizing the powder or granules is supplied into the processing vessel through an air flow straightening plate consisting of a perforated plate provided in the lower part of the processing vessel. 8. The fluidized bed granulation and coating method according to claim 7, wherein the powder particles are spherical granules and are coated by spraying a coating liquid. 9. The fluidized bed granulation and coating method according to claim 7 or 8, wherein the coating is a coating liquid containing a pharmaceutical agent. 10. A method for fluidized granulation and coating, comprising the steps of: supplying air from an air inlet duct into a cylindrical processing vessel having a truncated conical section tapering downward; simultaneously discharging the supplied air from an exhaust duct to fluidize the powder or granules in the processing vessel; and spraying a binder or coating liquid and compressed air independently from the truncated conical section below the interface of the flowing powder or granules near the inner wall of the truncated conical section, where the flowing powder or granules have a high density, to the vicinity of the wall; granulating or coating the powder or granules while controlling the temperature of the compressed air supplied to a spray nozzle and/or a compressed air ejection nozzle, and/or the air stream fluidizing the powder or granules, based on temperature measurements of the air flow in a pipeline for supplying the compressed air and/or the temperature measurements of the powder or granules to be fluidized; and supplying the air stream fluidizing the powder or granules into the processing vessel through an air flow straightening plate consisting of a perforated plate provided in the lower part of the processing vessel. 11. The method of claim 1, wherein the powder particles are spherical granules and the coating liquid is sprayed to coat the particles.
10. The fluidized bed granulation and coating method according to claim 0. 12. The fluidized bed granulation and coating method according to claim 10 or 11, wherein the coating is performed using a coating liquid containing a pharmaceutical agent.