Fluidized bed granulation equipment is currently widely used in the production process of traditional Chinese medicine, with significant advantages. This method is a technology that integrates mixing, granulation, drying and even coating in a fully closed container. Compared with other wet granulation, It has the characteristics of simple process, short operation time and low labor intensity. At present, fluidized bed granulation technology is getting more and more.
The wider the application, the smaller the gap between the fluidized granulators produced at home and abroad. This technology is of great significance to the development of the modernization of Chinese medicine production in my country. This paper briefly discusses the common problems encountered in the production of traditional Chinese medicine by fluidized bed granulation equipment.
Fluidized bed granulation, also known as boiling granulation, fluidized spray granulation or one-step granulation, etc. Compared with other wet granulation methods, the method has the characteristics of simple process, short operation time, low labor intensity, etc., and reduces material handling. The number of times and the time required for each process are shortened, thereby reducing the pollution to materials and the environment.
Fluidized bed granulation technology has the advantages of fast mass transfer, high heat transfer efficiency, uniform particle size, low density, good fluidity, and good compression moldability. There is little or no migration of soluble components between particles, which reduces the possibility of uneven tablet content; PILOTECH YC-03 Fluidized bed granulation can automatically pump materials, and materials can automatically complete mixing, granulation, It can be used for drying, coating and other processes, and can be self-weighted under the equipment. It is an ideal advanced pharmaceutical equipment that conforms to GMP standards. At present, the fluidized bed granulation technology is being used more and more widely, and the gap between the fluidized granulators produced at home and abroad is getting smaller and smaller. This technology is of great significance to the development of the modernization of Chinese medicine production in my country.
Fluidized bed granulation principle and equipment
1.1 Fluidized bed
Fluidized bed refers to a solid particle bed formed by rapidly blowing air (inlet air) from bottom to top, passing through fixed particles and maintaining solid particles in a state of continuous reciprocating motion. When the air inlet rate starts to rise from zero, the pressure difference on both sides of the fixed particle bed also begins to increase; when the pressure difference between the two sides of the material is equal to the effective weight of the fixed particle bed, the particles begin to move. The state is called the initial fluidized bed. When the fluid flow rate in the fixed bed stage increases to the point where the solid particles move relative to each other, and then increases the fluid flow rate, the solid particles move violently in the bed, and the bed is fluidized. When the fluid velocity is greater than the settling velocity of the solid particles, the fixed particles cannot continue to stay in the container, but are carried out of the container by the airflow.
The formation of particles is that when the binder is sprayed evenly on the suspended and loose materials, the binder droplets wet the powder in contact and coalesce around themselves to form particle nuclei, and at the same time, the continuously sprayed droplets fall on the particles. Bonding and bridging occurs on the surface of the core, so that the particle cores and the particle cores and between the particle cores and the particles are cross-linked and combined, and gradually agglomerate and grow into larger particles. The purpose of granulation is that tablets and capsules need to use granulation to improve the fluidity and compressibility of the granules, so as to facilitate filling, dosage and tableting; granules, pellets, drop pills, etc. must be formed by granulation; prevent Dust flying and adhesion on the wall of the device meet the requirements of GMP; after the drug is granulated, the preparation can produce the expected quick-acting or long-acting effect, etc. The main factors affecting fluidized granulation are the properties of the fine drug powder, the amount of material in the granulator, the type of binder, the concentration of the binder, the spray speed of the binder, the pressure of the spray air, and the air intake volume. size, inlet air temperature, drying time and temperature, etc.
1.2.1 Agglomeration and granulation The drug powder (primary particles) added to the container is in the fluidization process, and after contacting with the sprayed adhesive, agglomerates, and gradually grows into the desired particles (secondary agglomeration particles), which are soft and non-toxic. rule. By selecting appropriate stirring, rotating, circulating, spraying, fluidizing and other conditions, any particle ranging from light amorphous particles to heavy spherical particles can be prepared.
1.2.2 Coating granulation takes the primary particle of the powder as the core particle, the surface of which is wetted by the spray adhesive and then contacts with other powders, and the powder adheres to the surface of the particle to form powder-coated particles, and the surface of the coated particle is once again sprayed with the spray. When the liquid and powder are in contact, the spherical particles required for the gradual growth of the powder are covered layer by layer.
We investigated the effect of fluidized bed atomization parameters on particle aggregation. The research shows that with the decrease of gas-liquid ratio, the decrease of atomization gas volume and the decrease of temperature, the particle aggregation rate increases. The analysis of the microstructure of the particles found that there were two different polymerization modes of the particles in the experiment, namely, coating granulation and polymerization, as shown in Figure 1.
1.3 Fluid bed drying
In the fluidized bed drying process, the temperature usually changes in three stages: in the first stage of drying, the temperature of the material is gradually heated from room temperature to the wet bulb temperature of the hot air; in the second stage, the material keeps the wet bulb temperature of the hot air unchanged. , until the moisture content of the material drops to the critical humidity, at which time the material no longer contains free moisture; then, it enters the third stage of temperature rise, and the material loses bound water. When drying, the inlet air temperature should not be too high, the solvent on the surface of the particles evaporates too quickly, and the inner layer of the solvent is blocked from diffusing outwards, resulting in a large number of particles that are dry on the outside and wet on the inside. If the temperature is too low and the drying time is too long, a lot of fine powder will be produced.
We have studied the granulation time of fluidized bed granulation. Studies have shown that it is necessary to find the critical point of granulation completion, which can both stop the further fluidization of the dried granules and avoid the attrition of the dried granules. The drying time increased with the increase of the moisture content of the adhesive solution, decreased with the increase of the inlet air flow rate, and decreased with the increase of the inlet fluidization air temperature.
1.4 Fluidized bed granulation device and process
The fluidized bed granulation device is mainly composed of air intake and exhaust device, container, gas distribution device (such as screen mesh, etc.), spray system, gas-solid separation device (such as dust bag), material in and out device, control system, etc. The intake air source is generally outdoor air. The air first passes through the primary (or medium-efficiency) filter and heater, and enters the container part containing the solid material bed from the lower part of the fluidized bed through the screen. The material is in a fluidized state, and then the peristaltic pump sends the binder solution into the spray gun tube, and the binder solution is evenly sprayed into a mist by compressed air, which is spread on the surface of the fluidized powder, so that the powders contact each other and aggregate into granules. After repeated spraying and drying, when the particle size meets the requirements, the spraying is stopped, and the formed particles continue to be dried by hot air in the bed and discharged. The particles rising to the top of the cavity with the airflow are blocked by the dust bag, and the airflow passing through the dust bag is then sucked away by the external exhaust fan. Generally, the factory installs a water curtain dust removal device at the outlet of the roof exhaust pipe, which overcomes the pollution of the powder particles in the pharmaceutical process to the environment. The top of the box of the water curtain dust removal device is equipped with a sprinkler head to form a water curtain. The airflow with dust passes through the sprayed water curtain, and the dust is absorbed by the water, settles to the bottom in the box, and is discharged through the sewage pipe.
2 Common problems and solutions in production
2.1 Drip gun
The drip gun is that the adhesive sprayed by the nozzle is not fully atomized, and coarse particles are made. Too many coarse particles will cause poor boiling effect of the particles, block the screen, and the later pressed tablets have spots. The causes include clogging of the nozzle, unstable compressed air, etc., which will cause the drip gun. If the nozzle is blocked, flush the gun and re-adjust the gun; if the compressed air is abnormal, stop spraying until the compressed air pressure is normal, or the auxiliary air pressure may not be turned on.
2.2 There are many fine particles or more coarse particles.
2.2.1 Reasons for the material When the material is too fine, it will adhere to the dust bag during the granulation process. When the material is discharged, the material will be mixed into the particles due to the backflushing effect of the dust bag, resulting in too much fine powder. When the material is too coarse, larger particles are produced during the granulation process. The auxiliary materials used in granulation generally require a fineness of 80 to 100 mesh, otherwise the obtained granules are prone to color spots and uneven particle size distribution.
2.2.2 Inlet air temperature If the inlet air temperature is too high, the droplets sprayed by the spray gun have been dried before being sprayed on the surface of the powder, and the formed particles are too small, and such particles can no longer adhere to fine particles after being quickly dried. If the inlet air temperature is low, the droplets will be larger, and the formed particles will be larger, while the wet particles can continue to adhere to the fine powder and produce coarse particles. The solution is to control the inlet air temperature.
2.2.3 Atomization pressure The larger the atomization pressure of the spray gun, the smaller the spray droplets, the smaller the particles and the more fine powder. The smaller the atomization pressure of the spray gun, the larger the spray droplets and the larger the particles formed. Adjust the compressed air pressure or the spray angle of the gun head to make the spray gun spray the appropriate droplet size.
2.2.4 The flow rate of the peristaltic pump The smaller the flow rate of the peristaltic pump, the smaller the spray droplets, and the smaller the particle size of the produced particles. The larger the flow rate of the peristaltic pump, the larger the spray droplets, and the finer adhesion. If the powder has more particles, “adjust the flow rate of the peristaltic pump to a suitable range”. Usually, the spraying speed is “slow; fast; slow.” It is better to control in three stages. It is especially important that when the particle size is large, the proportion of fine powder is very small, and a small amount of liquid should be sprayed at a slower speed. Prevent the particles from sticking to each other and form agglomeration, resulting in the entire granulation process fail.
2.2.5 Fan speed The actual fan speed is high, the collision between particles is more intense, and the obtained particles are smaller. “The actual fan speed is low, the boiling effect is not good, the moisture of the particles evaporates slowly, and the produced particles are too large” Adjust the fan speed to change the actual fan speed.” However, it should be noted that the actual fan speed is too different from the set fan speed. It can be considered that wet particles may accumulate and adhere to the screen, or the water in the water curtain dust removal cabinet has accumulated. too much, resulting in increased wind resistance. “The solution is to change a screen at an appropriate time to clean up the water in the dust removal cabinet.
2.3 The particle yield is low
If the continuous particle yield is not within the normal range, a large amount of powder or particles may leak from the dust bag due to the damage of the dust bag. The solution is to check whether the dust bag in the machine is damaged, and replace the damaged dust bag. dust bag.
2.4 The phenomenon of collapsed bed
The phenomenon of bed collapse is that in the process of granulation, the solid bed in a fluidized state loses its rising power in a short period of time, and finally becomes in a static state, and the phenomenon of sticky sieve or large-area agglomeration occurs, resulting in low production efficiency. The main reasons are that the traditional Chinese medicine dry extract powder has strong viscosity and hygroscopicity; the adhesive spray rate is too fast; the inlet air temperature drops; the inlet air humidity changes; the atomization pressure decreases; the process design is unreasonable, etc.” First turn off the spray system immediately, then gradually find out the reason, adjust it to a normal state, and then continue production.
2.5 Ditch bed phenomenon
The phenomenon of the air ditch bed is that there is a short circuit in the air flow in the container, and the air inlet air quickly passes through the local powder, while other materials are in a relatively slow motion or static state. “The reason may be that the local humidity of the material is high.” The solution can be stopped first, Re-spread the material and start the operation again.
3 Improvement of fluidized bed granulation equipment
The fluidized bed equipment has many components, and consumes a lot of electric energy and thermal energy. “The electric energy consumption mainly comes from the fan. At present, the energy-saving method of the high-power fan mainly uses the frequency converter to control the fan to achieve the purpose of energy saving” and shorten the production process of the fan. The necessary use time can also achieve the purpose of energy saving. “The consumption of heat energy mainly comes from steam equipment. The way to save energy is to avoid increasing energy consumption due to excessive drying of the product: reduce the initial moisture content of the material: take thermal insulation measures to improve the performance of the equipment.
It is relatively difficult to clean the dust bag of the fluidized bed equipment. Improper operation will cause certain personal injury. Design safety measures with high safety performance to prevent possible accidents. For example, when the dust bag falls rapidly, its safety device can be quickly tightened. , slow down the falling speed of the dust bag as a whole until it stops.