Current situation and Prospect of fluidized bed technology in pharmaceutical industry

Fluidized bed is also called fluidized bed The application of fluidized bed technology in China's pharmaceutical industry dates back to the 1980s It has developed from the original fluidized bed drying to the application of fluidized bed mixing, fluidized bed coating, fluidized bed granulation (pill) and fluidized bed comminution It has developed from the original solid preparation to other preparations, especially in granulation and drying Outstanding contribution It can be said that the fluidized bed technology is of great significance for the development of pharmaceutical industry in China The fluidization performance of materials given by fluidized bed will extend more applications Now it is necessary for people to carry forward this classic technology Starting from the basic concept of fluidized bed, this paper analyzes and compares the current situation of the application of fluidized bed in pharmaceutical industry, expounds the characteristics of several fluidized bed equipment, and looks forward to the development and application prospect of fluidized bed technology 1 Basic concept of fluidized bed 1.1 concept of fluidization phenomenon in an equipment, the particle materials are stacked on the distribution board When the gas flows into the bed from the lower part of the equipment, with the increase of the air flow speed to a certain extent, the solid particles generate boiling state on the bed, which is called fluidization, and this bed is also called fluidized bed This method can be used in the drying, granulating, mixing, coating and crushing of materials Due to different characteristics of solid particles and different factors such as bed and air flow speed, there can be three types of bed, as shown in Figure 1 V < VMF V ≥ VMF VMF < V < VT V ≥ VT dead bed fluidized bed (1) * stage (fixed bed) When the fluid velocity is low, although the solid particles contact with the fluid in the bed, the corresponding position of the solid particles does not change At this time, the state of the fixed particles is fixed bed; (2) In the second stage (fluidized bed), when the velocity of fluid in the fixed bed stage gradually increases to a certain point, the solid particles will move to each other's position If the velocity of fluid is increased again, and the pressure loss of the bed remains unchanged, the solid particles will move irregularly in the bed, and then the bed will be in fluidization; (3) In the third stage (air transportation), when the flow velocity of the fluid is greater than the settling velocity of the solid particles, the solid particles can not stay in the container, but are brought out of the container by the air flow For pharmaceutical industry applications, drying, granulation, mixing, coating, etc are operated in the second stage, while for comminution, they can be operated in the second stage and the third stage 1.2 the concept of fluidization can be divided into two types, i.e dispersion type and aggregation type, while the majority of fluidization encountered in general fluidized bed is aggregation type In the polymer fluidization, the solid particles appear not in a single form, but in the form of particle clusters In the application of fluidization technology in pharmaceutical industry, the density of solid particles and fluid is quite different (for example, the density of hot air and inert gas is very small) In practical application, improper design of process parameters and equipment is easy to cause "ditch flow" and "surge" phenomenon, as shown in Figure 2 When the fluid flows into the fixed bed, because of various reasons, the fluid distribution in the bed is not uniform, resulting in short circuit in the local part of the bed, making quite a lot of fluid flow through the bed through the short circuit If "ditch flow" is generated, the convective bed drying equipment will cause poor contact between the drying medium and the dried material and reduce the drying effect (2) "Tengchong", when the particle size distribution in the fluidized bed is uneven, the gas passing through the distribution is extremely uneven, and the height and diameter of the fluidized bed are relatively large, the bubbles in the bed will converge and grow up until the bubble diameter is large enough to be close to the inner diameter of the bed, the solid particles will form a piston in the bed to move upward, the particles will throw up very high, and the small particles will be entrained by the air flow, Big particles then fall Such circulation will also make the solid particles in poor contact with the drying medium fluid and reduce the drying effect Analysis of the application of fluidized bed technology and equipment in pharmaceutical industry The fluidized bed technology Zui was used in the drying industry as early as 1948 when the dol Oliver solid fluidization device was established in the United States In China, the fluidized bed technology began to be applied after 1958, first in the salt industry, and then it was widely used in fertilizer, pigment, plastic, pharmaceutical and other aspects Among them, its real application in the pharmaceutical industry was after 1980, when it was only used in solid state Drying of system agent Nowadays, the fluidized bed technology has developed from the simple fluidized bed drying to the fluidized bed coating, the fluidized bed pelletizing, the fluidized bed mixing and the fluidized bed pulverizing in the pharmaceutical industry, especially in recent years, it has extended to the coating, the pelletizing (pill) function, and the new function shows more advantages compared with the original traditional preparation process 2.1 analysis of current situation of fluidized bed drying technology and equipment 2.1.1 analysis of drying characteristics of fluidized bed drying the hot air flow is used to make the wet particles suspended, the fluidized boiling makes the material heat exchange, and the moisture is taken away to dry The hot air flow is used to carry out the mass and heat transfer of gas-solid two-phase suspension contact to dry the wet particles 2.1.1.1 the advantages of fluidized bed drying (1) due to the large contact area between materials and drying media, and the continuous fierce agitation of materials in the bed, it is characterized by good heat transfer effect and relatively uniform temperature in the bed, high heat capacity coefficient (or volume heat transfer coefficient), generally up to 8000 ~ 25000kj / (M3 · h ·℃), and large production capacity; (2) Due to the uniform temperature distribution in the fluidized bed, which avoids any local overheating of the product, it is especially suitable for drying some heat sensitive materials; (3) it can be operated continuously or intermittently in the same equipment; (4) the residence time of the materials in the dryer can be adjusted as required, so the moisture content of the product is stable; (5) There are few moving parts in the drying device, so the investment cost of the equipment is low and the maintenance workload is small 2.1.1.2 the disadvantages of fluidized bed drying (1) the particle size of dried materials has certain, which is generally required to be no less than 30 μ m and no more than 4 mm The particle size is too small to be entrained by air flow, and the particle size is too large to be fluidized; (2) when several materials are mixed for drying, the relative density of several materials shall be close; (3) The materials with high moisture content and easy to agglomerate are generally not applicable At the same time, the materials with high moisture content and easy to agglomerate will produce wall agglomeration and bed plugging in the fluidization process; (4) Due to the fierce backmixing of materials in the fluidizing dryer, the residence time of materials in the single-stage continuous fluidizing dryer is not uniform, which may lead to the discharge of non dried materials from the bed together with the products 2.1.2 analysis of current situation of fluidized bed drying equipment fluidized bed drying, also known as boiling drying, uses hot air flow to suspend wet particles, fluidized boiling makes material heat exchange, and takes water away to dry It adopts convection drying method, gas-solid two-phase contact in a large area, showing the characteristics of boiling drying, such as small bed temperature difference, fast drying speed and even water content of finished products, which is widely applied to varieties with large output Fluidized bed drying equipment is often used in pharmaceutical industry, such as horizontal fluidized bed dryer, fluidized bed dryer, etc 2.1.2.1 the fluidized bed dryer is composed of air filter, heater, main machine of fluidized bed, cyclone separator, bag filter, high-pressure centrifugal fan and operation platform as shown in Figure 3 When the powdery and granular solid materials are added into the fluidized bed dryer by the feeder, the filtered clean air is heated and then sent to the bottom of the fluidized bed by the blower, which contacts with the solid materials through the porous distribution plate, forming the fluidization to achieve the heat and mass exchange of the gas and solid After the materials are dried, they are discharged from the discharge port, and the waste gas is discharged from the top of the fluidized bed, which is recycled by the cyclone dust collector group and the bag type dust collector Empty The fluidized bed dryer is capable of continuous feeding and discharging, and has the characteristics of large output At present, it is mainly used in the production of traditional Chinese medicine granules But its production effect is not satisfactory, the main reasons are: (1) the original structure design has defects, the structure can not effectively avoid cleaning dead angle and blind area; (2) in the real sense, it can not meet the requirements of continuous feeding and discharging There are many imitations of this type of model in China, but they can not be separated from two representative models abroad One is ventilex company in the United States, which has achieved a single unit evaporation capacity of 5000kgh2o / h; the other is GF series products of Glatt company in Germany, which has achieved a single unit evaporation capacity of 1600 kgH2O / h The main differences between domestic models and these two types of equipment are as follows: (1) zero pressure design and control of bed; (2) design of dust recovery device and series; (3) quick disassembly structure designed for cleaning SOP; (4) effective recovery device of organic dissolved coal 2.1.2.2 the air of the boiling dryer as shown in Figure 2 is heated and purified, and then led in from the lower part by the induced draft fan through the porous mesh plate of the hopper In the working room, the fluidization is formed by mixing and negative pressure After the water evaporates rapidly, it is carried away with the exhaust gas and the material is dried rapidly The characteristics of the fluidized bed dryer are: (1) the fluidized bed is of circular structure to avoid dead angle; (2) the bed is equipped with agitation to avoid the agglomeration of wet materials and the formation of ditch flow "ditch flow" in the drying process; (3) it is convenient, quick and thorough, easy to operate, and convenient to clean; (4) it is operated under sealed negative pressure, without dust leakage; (5) The drying speed is fast and the temperature is even The drying time of each batch is generally 20-30 minutes The machine is designed for wet particle drying Because of its simple structure and low price, it has been widely used in pharmaceutical factories in China, and its proportion in foreign countries is very small The problem to be solved is: because of the internal mixing structure, the sealing and quick unloading cleaning should be overcome 2.2 fluidized bed granulation (pellet) technology and equipment status analysis 2.2.1 fluidized bed pelletizing (pellet) characteristics analysis of fluidized bed granulation is in the fluidized bed drying process assisted binder spray process, fluidized bed granulation is also called one step granulation, which combines mixing, granulation, drying in one The principle is that the powder particles are fluidized and mixed by air flow The adhesive is sprayed on the powder by airflow spray to make it agglutinate, and hot air flow is used to conduct the heat transfer of gas-solid two phase suspension contact to dry particles 2.2.1.1 the advantages of fluidized bed granulation (1) the combination of mixing granulation drying, the mixing time, moisture content of the product, the granulation quality and uniformity after drying, etc meet the corresponding requirements; (2) the granulation finished product particles are relatively loose, the particle size is about 20-80 mesh, and the appearance of the finished product is nearly spherical, with good fluidity; (3) high production efficiency and low labor intensity; (4) The mixing, granulating and drying process shall be in the fully closed negative pressure state to prevent dust pollution and flying and low external pollution 2.2.1.2 disadvantages of fluidized bed granulation (1) high power consumption; (2) relatively difficult cleaning; (3) improper control is easy to produce pollution In recent years, the development of pneumatic swirl fluidized bed can not only produce particles but also coat them At the same time, porous spherical particles or pellets can be produced by centrifugal fluidized bed pelletizing, which is suitable for mass production of high density and small diameter particles Because these technologies can finish coating at the same time of fluidizing granulation or pelletizing, it is included in 2.3 fluidized bed coating 2.2.2 analysis of current status of fluidized bed granulation (pelletizing) equipment 2.2.2.1 boiling