One of wet granulation: fluidized bed granulation
The mechanism of particle growth during fluidized bed granulation is divided into: coating growth and agglomeration growth. The growth of the coating means that the adhesive is spread on the surface of the particles in the form of droplets, and the layers are wrapped to make the particles grow. The agglomeration refers to a liquid bridge or solid formed by two or more particles formed by a binder. The bridges are reunited to make the particles grow.
After the granulation, the particle size distribution is wider and the fine powder is too much.
1.1 In the fluidized bed granulation process, the problems often encountered are:
(1) The fan frequency is too high or the position of the spray gun is high, which increases the dissolution and volatilization of the binder, so that the material cannot be completely wetted, and a stable solid bridge cannot be formed between the particles, which exhibits a spray drying phenomenon and blocks the agglomeration of the particles.
(2) The amount of binder is small, increasing the amount of binder used, forming a solid bridge between more particles, promoting particle growth
(3) The type or concentration of the binder is not suitable, and a stable solid bridge cannot be formed between the particles. It is recommended to replace the adhesive with a higher viscosity, but at the same time, it should be noted that the strength of the adhesive is too large to cause the gun to block.
(4) The spray range of the spray gun is smaller than the material bed area, which causes the intermediate material to form larger particles due to contact with more adhesive, while the peripheral material has smaller particles due to less contact with the adhesive. At this time, the spray range of the spray gun should be adjusted to be the same as the material bed area (if the spray range of the adhesive is too large, the material will adhere to the wall). In addition, the fluidization state of the material can also be adjusted. If the fluidization state of the material is good, the particle size distribution of the material particles can be narrowed.
(5) If there is still too much fine powder after the amount of the binder is increased, it may be due to the binder.
1.2 The obtained granules have larger granules and even collapsed beds.
The reason for the larger size of the particles is that the binder does not dry out in time after contact with the particles, and the binder forms a liquid bridge between the plurality of powder particles to agglomerate the material into larger particles. Methods to prevent the formation of larger particles or bed-splitting are:
(1) Increasing the atomization pressure or reducing the liquid supply speed, so that the droplets are reduced, and the binder is dried in contact with the particles in time to prevent the binder from agglomerating with a large amount of materials.
(2) Increase the frequency of the fan, improve the fluidization state of the material, and prevent the material from sticking to the joint.
(3) Increasing the inlet air temperature so that the droplets can be dried in time after contact with the particles to prevent the material from continuing to grow.
(4) Pay attention to the air humidity. When the air humidity is high, the drying efficiency of the material is reduced. Therefore, the liquid supply speed should be lowered or the inlet air temperature should be increased.
(5) When there are low-temperature melting materials in the material, attention should be paid to controlling the inlet air temperature and fluidization state to prevent the local temperature from being too high, and the material melts to block the distribution plate, causing the material to agglomerate or collapse.
1.3 In the granulation process, the powder is blocked by the spray gun head
(1) The fan frequency is too high or the position of the spray gun head is too low, causing the boiling material to be too close to the spray gun head, causing the material to stick to the spray gun head to cause the gun to be blocked.
(2) The feed rate of the material is too high, so that the wet material cannot be dried in time, and the fine powder sticks to the spray gun head. The longer the material, the more material, and finally the gun is blocked.
(3) The viscosity of the binder is large, and there are insoluble particles in the binder, which easily causes the gun to be blocked. Therefore, when the binder is a suspension, it should be sieved before use.
1.4 The content or yield of the obtained pellets is low
(1)in the process of drawing, the collecting bag of the fluidized bed can only collect more than 20μm of material. If the particle size is small, the fine powder is easily blown away by the airflow, or adsorbed in the trap due to static electricity, so the bag can not completely collect the drug. Therefore, pay attention to the particle size of the material and less material loss.
(2) At the beginning of the granulation, the air volume should be small, because the granules have not yet formed at this time, and the air volume is too large to blow away the powder, and the content is easy to be low; As the granulation time increases, the particles form, the material density increases, and the air volume needs to be adjusted in time. After the adhesive is sprayed, it gradually enters the drying stage, the binder solvent evaporates, the particle density decreases, and the air volume needs to be gradually reduced.
(3) For lower-level drugs, when granulating, the drug is generally added to the binder, and the drug is evenly sprayed onto the material together with the binder. However, pay attention to controlling the fan frequency and liquid supply speed, reducing spray drying and reducing material loss.
1.5 The obtained pellets are dry outside and wet inside
(1) The inlet air temperature of the fluidized bed is too high, the solvent on the surface of the particle evaporates too quickly, and the solvent in the inner layer is diffused outward, and the temperature of the material should be appropriately lowered.(2) After the material with low baking point is melted and agglomerated, it is easy to find the wet phenomenon inside the material when discharging. Therefore, if there is a material with a lower melting point in the material, attention should be taken to exclude the cause of the material melting.
1.6 During the process of granulation, the material is seriously static
At the beginning of fluidized bed granulation, the static electricity of the material is the most serious. It can be used to increase the liquid supply speed, increase the air humidity, or add a small amount of micro-silica gel, which is also very helpful for the elimination of static electricity.In addition, the smaller the particle size of the material, the more severe the static electricity during granulation and the more serious the material adherence. The material size can be increased moderately.
Post time: Sep-03-2019