JPH0369575B2 - - Google Patents

Description

[Detailed description of the invention]

<Industrial Field of Application> The present invention relates to an apparatus for producing fine granules (medicinal products made into fine granules) defined in the Ninth Edition Japanese Pharmacopoeia. <Conventional technology> Generally, according to the fluidized granulation method, the raw material 10μ
This process is carried out by placing a certain amount of powder and granules in a granulation drying tank, fluidizing it with hot air blown in from below the screen, and at the same time supplying the binding liquid in the form of a spray from a spray nozzle installed in the tank. By promoting the aggregation effect between particles, it is possible to obtain, for example, a granulated product with a size of 200μ or more. However, since such a fluidized granulation method is a new granulation method that has recently been developed, the relationship between various factors has not yet been fully elucidated even when attempting to obtain a desired particle size. For this reason, conventionally, when fine granules requiring strict quality had to be manufactured, the granules had to be sieved through a sieving process after the granulation process was completed. <Problems to be solved by the invention> According to the Ninth Edition Japanese Pharmacopoeia, the particle size distribution of fine granules is defined as "75% or more of particles between 500 and 105μ, 5% or less of particles of 500μ or more, and 10% of particles of 74μ or less. % or less.” In order to stably granulate particles with a particle size distribution that satisfies the standards for "fine granules" stipulated in the Ninth Edition Japanese Pharmacopoeia, the present inventors investigated various factors and their effects on the particle size of granulated products. As a result of our research, we found that the clogging of the back filter installed at the top of the tank, the temperature and humidity of the hot air supplied from below the screen, the amount of binding liquid supplied from the spray nozzle and its moisture content, etc. are important along with the granulation time. We found that this is a contributing factor. Therefore, in order to simplify the control system of manufacturing equipment,
As a result of further research to understand the interrelationships between factors and narrow down the number of factors, we found that if the moisture content of the granules in the tank during granulation is constant, the desired result can be achieved despite fluctuations in other factors. It has been found that it is possible to stably obtain particles of uniform particle size that correspond to fine granules. On the other hand, in the fluidized granulation method, unlike other granulation methods, compressed air and granulation liquid are ejected into the tank, and during granulation, the granules become atomized and flow inside the tank. It is believed that it is difficult to easily and stably measure the moisture content during granulation due to the large number of disturbance factors, and the challenge was how to achieve this. Therefore, the present inventors installed a moisture detector at a specific location in the tank, and determined the electrical resistance value directly measured by the moisture detector and the actual moisture content of the powder itself during granulation. As a result of considering the interrelationship with It was found that an extremely close correlation was maintained between the two. Based on this knowledge, we were able to control the particle size of granules with high precision, and in particular, we completed an apparatus that can stably produce "fine granules" according to the Japanese Pharmacopoeia. <Means for Solving the Problems> The fine granule manufacturing apparatus of the present invention consists of a tank in which an inverted truncated conical inclined part is continuously formed below a cylindrical straight tower part, and a horizontal part is provided on the bottom of the tank. The powder to be treated is placed on a stretched screen, and atomized liquid is supplied from a spray nozzle placed above the screen, and pressurized gas is sent into the tank from below the screen. Granulation is performed by adding
In a batch type apparatus for obtaining a dry granulated product by cutting off the supply of the atomized liquid and continuing to feed the pressurized gas after granulation is completed, near the inner wall of the inclined part of the inverted truncated cone, A moisture detector is provided, which consists of a pair of electrode plates facing each other, with the normal line of the electrode surfaces extending in the circumferential direction of the tank, and the moisture content of the powder during granulation is measured from the electrical resistance value between the electrodes. The apparatus is characterized in that the water content of the binding liquid supplied to the spray nozzle is automatically controlled in such a direction that the deviation between the measured water content value and the set value becomes zero during the period when granulation is being performed. <Operation> Prior to the start of fluidized granulation, the powder to be treated is stored in the tank. The amount of powder and granules at this time is usually charged into the inverted truncated cone portion. In this case, the moisture detector is submerged in the powder. Next, when fluidized granulation is started, compressed air is introduced from below the screen, and the atomized binding liquid is sprayed from the spray nozzle. As a result, the stored powder to be processed rises along the axis, and the rising particles combine with the binding liquid and then flow from the top to the bottom along the slope. Since the moisture detector is installed near the inner wall of this slope, it does not directly receive the compressed air sent from below the screen or the moist binding liquid immediately after being ejected from the spray nozzle. Moisture can be detected in a stable, high-density particle flow with no turbulence. At the start of granulation, the raw material is a powder or granule of about 10 μm in size, and as it is repeatedly combined with a water-containing binding liquid, the particle size gradually increases as agglomeration between particles progresses. The larger the moisture value measured by the moisture detector, the larger the average particle size. The moisture detector of the present invention ranges from small particles that are blown up high in the center of the tank and circulate in a large loop, to particles that enlarge and become heavy and circulate in the lower part of the tank in a small loop. up to large particles,
It is located in a position where everything passes through, and accurate moisture values can be detected continuously from the start of granulation to the end of granulation. In the action diagram in Figure 3, the period between the starting point and point A is the preliminary granulation process until the moisture content reaches the set value, and the period between point A and B is the main granulation process where the moisture content is controlled at a constant value. These two processes together constitute a granulation process, and the next step after point B is a drying process, and when a dry state with zero moisture is reached, one batch process is completed and the granules are taken out. <Example> Hereinafter, an example of the present invention will be described based on the drawings. FIG. 1 shows an overall configuration diagram of an embodiment of the present invention. The fluidized granulation drying tank 1 has a shape in which an inverted truncated conical inclined part is continuously formed below a cylindrical straight tower part, and a screen 2 on which the powder and granules are placed and through which air passes is horizontally placed on the bottom of the inclined part. A hot air inlet 3 is connected to the bottom of the screen 2, and a spray nozzle 4 that sprays atomized binding liquid downward is installed in the center of the tank facing the hot air inlet 3. A back filter 5 is provided at the top of the tank to prevent the granules from flowing out, and an exhaust port 6 is provided at the top end of the tank to discharge excess air from inside the tank. Steam-heated air is supplied to the air inlet 3 through an air supply damper 7 and a steam heater 8,
Air in the tank is forcibly exhausted from the exhaust port 6 through an exhaust damper 9 and an exhaust fan 10. The binding liquid is supplied from the binding liquid tank 11 to the spray nozzle 4 through the liquid feeding pump 12 and the binding liquid flow rate adjustment valve 13, while pressurized air is supplied to the spray nozzle 4 through the spray air flow rate adjustment valve 14.
is supplied to the spray nozzle 4 through which the binding liquid is sprayed. A pair of opposing electrode plates made of a conductive material such as copper or stainless steel are insulated in the powder tank in a stationary state near the inverted truncated conical slope in the tank 1, that is, slightly above the periphery of the screen 2. A moisture detector 15 fixed on a base is arranged. The direction of this electrode plate is the direction in which the normal line of the electrode plate surface forms the circumferential direction of the tank, that is, the direction in which the fluid resistance to the powder and granular material flowing along the longitudinal section passing through the axis of the tank is minimized. provided. The control circuit 16 is
The signal from this electrode is used as a feedback signal, and the signal from a setting device that can be freely set is used as a reference signal.
The deviation is detected and during the granulation process,
The opening degrees of the binding liquid flow rate control valve 13 and the spray air flow control valve 14 are continuously controlled based on the deviation value, and in the drying process after the spraying of a predetermined amount of binding liquid is completed, the binding liquid flow rate control valve 13 and the spray air flow control valve 14 are controlled continuously. 13 and spray air flow control valve 14. The measurement of the electrical resistance value between the electrodes in the present invention is as follows:
In addition to directly measuring the electrical resistance value, it may be determined indirectly by measuring the electrical conductivity or current value. If the space between the electrodes of the moisture detector 15 is too large, the fluidized granules will not pass through it smoothly, and if it is too wide, the sensitivity will decrease and electrical conductivity may be lost. According to experiments, good results were obtained when the thickness was 10 to 20 mm. In addition, the voltage applied between the electrodes may be either alternating current or direct current, but if the voltage is very small, an amplifier circuit etc. will be required, which will complicate the device. Good measured values were obtained. Figure 2 shows the interelectrode resistance value (MΩ) of the moisture detector and the powder and granular material used in the test when a test was conducted using the device of the present invention equipped with an electrical resistance type moisture detector. The water content value itself is plotted. What should be noted in this graph is that for a wide range of moisture content from 5% to 13%, which is sufficient for practical use, the plots of the moisture detector measurement data and the moisture content of the powder or granular material itself, which is the object to be measured, line up on a straight line. It's on. This means that according to the present device, the correlation between the measured resistance value and the moisture content of the powder or granular material in the experiment is reproduced with high accuracy. The conditions under which this test was conducted were as follows. Moisture detector electrode conditions Electrode dimensions 40mm x 30mm square Between electrodes 20mm Binding liquid formulation Raw material powder Lactose: Cornstarch 85:15 Charge amount 16Kg Binder 5%HPC-L Operating conditions Supply air temperature 90℃ Supply air amount per unit The opening of the control valves ¹³ and 14 is controlled by the output signal of the control circuit 16. When the measured moisture value in the tank decreases below the set value, the combined liquid flow control valve 13 is operated to increase the combined liquid. On the other hand, when the measured water content in the tank increases beyond the set value, the binding liquid is operated to decrease. In this case, at the same time, the opening degree of the spray air flow control valve 14 is controlled to make the spray droplet diameter the same. <Effects of the Invention> According to the present invention, a moisture detector is provided near the inner wall of the inverted truncated conical slope of the tank, and while monitoring the moisture measurement value, granulation is carried out in batches, which are stored in the tank in advance. Since granulation is performed by applying an atomized liquid to the granular material, even if there is a disturbance factor, the moisture value can be accurately measured without being affected by it. By continuing the process of fluidized granulation while controlling the moisture content to a constant value as shown in Figure 3,
A heavy granulated product with a sharp particle size distribution and a high density and compactness can be obtained. Therefore, it has become possible to stably produce "fine granules" according to the Ninth Edition Japanese Pharmacopoeia, which was previously difficult. Further, according to the present invention, a pair of electrode plates are provided whose normal line to the electrode surface is in the circumferential direction of the tank, and the water content of the powder during granulation is measured from the electrical resistance value of the electrode plates.
It does not disturb the flow of the powder and granules flowing along the longitudinal section passing through the axis of the tank, and the powder and granules do not adhere to and accumulate on the electrode plate.
Moisture changes during the granulation process can be measured with high sensitivity and accuracy. Further, according to the present invention, the process proceeds from the start of the granulation process to the end of the drying process while the material to be treated remains hermetically housed in the tank, which is very sanitary. Next, the effects of the present invention will be explained with reference to some test examples. Test Example 1 and Comparative Test Example 1 Figure 3 shows the change in measured values by the tank moisture detector when moisture control is performed using the above-mentioned example device (solid line) and when moisture control is not performed (dotted line). shows. Table 1 shows how the presence or absence of such moisture control affects the particle size distribution and density (crude specific volume) of the resulting granulated product. When moisture control is not performed (comparative test 1), the particle size distribution is greatly spread;
Moreover, the crude specific volume is also relatively high. On the other hand, when moisture was controlled (Test Example 1), the particle size distribution became sharper, and the subsequent steps of tabletting, capsule filling, and
Even when packaging, etc., a heavy product with good workability can be obtained, and it is simply a "fine granule" in the 9th revised Japanese Pharmacopoeia.
We obtained an excellent "fine granule agent" that not only met the specifications but also had a much sharper particle size distribution.

【table】

[Table] Test Example 2 Next, various abnormal conditions were randomly set and tests were conducted to see how they would affect the granulated product. The supply air temperature from the air inlet is normally 80℃, but due to a setting error, the temperature is abnormally low 45 to 50℃.
℃, the granulation time was longer, but the moisture content was kept constant during granulation, so a granulated dry product of the same quality was obtained. The results are shown in Table 2. In addition, in the following test examples, the set resistance value
2MΩ, controlled moisture 8%.

[Table] Test example 3 Absolute humidity of air from air inlet 0.007Kg
When using dehumidified air such as H ₂ O/Kgdry Air, although the granulation and drying speeds are affected, the moisture content is kept constant during granulation, resulting in a granulated product of the same quality as Test Example 1. Obtained.

【table】

[Table] Test Example 4 When granulation was performed with the back filter in the tank becoming clogged and the supply air volume reduced to 7.5 ^m3 per minute, the flow state was slightly affected, but moisture was kept constant, so a granulated product of comparable quality to Test Example 1 was obtained.

[Table] Comparative Example A comparative test was conducted under the same test conditions as in the example described above, except that only the location of the moisture detector was changed to the lower end of the straight body of the fluidized granulation drying tank 1. . Samples were taken at the time of granulation, and Table 5 shows the moisture content of the particles and the measured resistance values at that time.

[Table] According to the data of this test, there is no correlation between the moisture content of the particles and the resistance value of the moisture detector. This shows that when the moisture detector is installed at the lower end of the straight body of the fluidized granulation drying tank, it no longer plays the role of a detector. Furthermore, when granulation was carried out using the apparatus of this comparative example and the particle size distribution of the obtained granulated product was investigated,
The data in Table 6 was obtained. Note that the resistance value is the fifth
Considering the data in the table, it was set to 30MΩ.

【table】 [Brief explanation of drawings]

FIG. 1 is an overall configuration diagram of an embodiment of the present invention, and FIGS. 2 and 3 are explanatory diagrams of the operation of the above embodiment. 1...Fluidized granulation drying tank, 2...Screen, 3
...Air inlet, 4...Exhaust port, 6...Spray nozzle, 11...Binding liquid tank, 12...Liquid feeding pump, 13...Binding liquid flow rate control valve, 14...Spray air flow control valve, 15...Moisture detector, 16
...control circuit.

Claims (1)

[Claims] 1 Consists of a tank in which an inverted truncated conical inclined part is continuously formed below a cylindrical straight tower part, and the granular material to be treated is stored on a screen stretched horizontally on the bottom of the tank, and the granular material to be treated is placed above the screen The atomized liquid is supplied from a spray nozzle installed in the tank, and granulation is performed by feeding pressurized gas into the tank from below the screen, and after granulation is completed, the atomized liquid is supplied. In a batch-type device for obtaining a dry granulated product by continuing to feed the pressurized gas while cutting off the gas, the apparatus comprises a pair of electrode plates facing each other near the inner wall of the inclined part of the inverted truncated cone. A moisture detector is installed in which the normal line of the electrode surface is in the circumferential direction of the tank.
The moisture content of the powder during granulation is measured from the electrical resistance value between the electrodes, and the moisture is supplied to the spray nozzle in the direction where the deviation between the measured moisture value and the set value becomes zero during the granulation period. A fine granule manufacturing device characterized in that it is configured to automatically control the moisture content of a binding liquid.