Views: 1 Author: Site Editor Publish Time: 2023-06-10 Origin: Site
In recent years, various active pharmaceutical ingredient importing countries have put forward higher requirements for the production process of Chinese pharmaceutical enterprises, so various certifications have rapidly spread in the pharmaceutical industry.
For raw materials, the focus of these certifications is on the refining, drying, and packaging process, so the reasonable choice of dryers is particularly important.
The choice of drying equipment should be based on the characteristics of the medicine and the ideal state of the finished medicine product, especially considering the material and sterility assurance of the sterile raw material drying equipment. At present, there are many types of API dryers in China, with different characteristics and applicable conditions.
▲ Vacuum drying oven for small and medium-sized trial production
The vacuum drying oven is an ancient drying device, which is divided into several layers by a heating plate. Fill the heating plate with hot water or low-pressure steam as the heating medium, place the material tray for drying on the heating plate, close the box door, and use a vacuum pump to vacuum the box. The heating plate heats the drug to the specified temperature in the circulating flow of the heating medium, and the water begins to evaporate and gradually withdraws with vacuum pumping.
This device is easy to control and can condense and recover evaporated solvents. During the drying process, drugs are not easily contaminated and can be used for drug drying, packaging sterilization, and heat treatment. In the 1980s, this equipment was commonly used as the main dryer in the raw material pharmaceutical industry. However, due to the difficulty in performing online cleaning (CIP) and online sterilization (SIP) on the material tray, the drying speed was slow, and the labor intensity of workers was high. In order to achieve drug uniformity, after drying, it had to be mixed in a powder mixing device. Nowadays, it is rarely used in large-scale production of raw material pharmaceuticals and is mostly used for medium and small-scale trial production or packaging material heat treatment.
▲ The vacuum rotary dryer must consider the sealing effect of the hollow shaft
Vacuum rotary dryers originate from double cone mixers and are mostly cylindrical bodies with two conical ends, also commonly known as double cone dryers. There are two hollow suspension shafts in the middle of the cone, which are used for equipment rotation support and channels for vacuum and hot water. The drug rotates while drying in the dryer, ensuring good uniformity of the entire batch of drugs. The hot medium enters the jacket through a hollow tube at one end, and the hot gas inside the device is discharged through the exhaust pipe in the hollow tube at the other end, and the volatile solvent is condensed and recovered. This equipment was developed by Shanghai Pharmaceuticals Industrial Research Institute in the 1980s. It was successfully used in penicillin production and soon popularized in the national antibiotic industry. At present, there are many domestic manufacturers. Later, similar products such as single axis rotary dryers, multi-dimensional rotary dryers, and inclined rotary dryers emerged. The supporting equipment of this drying equipment includes vacuum system, solvent recovery system, cleaning and sterilization system, etc.
Because of its simple operation, intermittent production, easy adjustment, online cleaning and online sterilization, this equipment has become a dryer for small and medium-sized antibiotic API enterprises, such as penicillin, lincomycin, Chlortetracycline, caffeine, etc. When selecting drying equipment, the main consideration is the concentricity of the two hollow shafts and the sealing of the hollow shaft. To ensure smooth operation of the equipment, the concentricity requires a shaft end runout of less than 0.01 millimeters. The sealing effect of the hollow shaft is mainly to prevent lubricant or filler contamination of drugs.
▲ The quality of domestically produced three-in-one equipment needs to be improved
Three in one refers to the combination of filtration, washing, and drying processes in the same equipment, which is very representative in the pharmaceutical industry. Three in one equipment has developed rapidly since the 1990s, and can be divided into several types based on the equipment form, such as belt type, tank type, and centrifugal type.
There are two types of belt type three in one: stepper type and continuous type. The main reason is that the advancing mode of the filter belt is different, and the workflow is completely the same. The material is evenly laid on the filter belt by the feeder, and the filter belt is dragged by the transmission device to move inside the flash dryer. Wash the solvent in the washing and filtration sections, and recover the solvent mother liquor through vacuum cold extraction; The hot air enters the drying section, is evacuated and condensed to recover the solvent. Used for large-scale batch production, suitable for drying granular materials with good breathability, and the finished product is evenly dried. It is widely used in the vitamin C and penicillin industries in China. Due to the relatively poor airtightness of this equipment, it cannot be well arranged for online cleaning and sterilization, so it is only suitable for the drying of non sterile raw materials and pharmaceutical intermediates. The feeder and filter belt correction device of this equipment play a crucial role in the normal operation of the equipment, and supporting facilities such as heaters and vacuum systems also have a significant impact on the equipment yield.
This type of equipment used in the pharmaceutical industry is mainly imported or self assembled with imported main components, while domestically produced equipment is only used in industries such as chemical, food, and traditional Chinese medicine. In recent years, companies have also imitated it in the pharmaceutical machinery industry, but successful applications in the pharmaceutical industry are not common.
The tank body of the tank type three in one equipment is similar to a large suction filter, with a chassis composed of a metal sintered plate filter, a support plate, and a heating plate. The tank body has a jacket for heating and cooling, and there is an agitator that can move up and down inside the tank. The agitator is a hollow structure, which is filled with medium for heating and cooling, and plays a main role in the drying stage. After the material enters the equipment, it is first subjected to suction filtration, followed by immersion in a washing medium for a certain period of time. Cold suction or pressurized suction filtration is carried out to a certain extent, and heating medium is introduced into the mixing, chassis, and jacket. At the same time, vacuum is pumped for drying. Based on experience and sampling, the drying is stopped and the material is discharged from the discharge port. The mixing seal and sintering plate of this equipment are crucial, and supporting equipment includes hydraulic system, vacuum system, heating and cooling unit, etc. Due to the fact that this equipment is fully enclosed, if an automatic discharge system is added, the equipment can fully achieve CIP and SIP, making it very suitable for the production of sterile raw materials.
In recent years, such equipment has been widely used in the production of penicillin sodium salts and semi synthetic antibiotics. In the 21st century, with the acceleration of GMP certification, China's pharmaceutical machinery industry is vigorously developing or imitating similar imported equipment. However, due to differences in processing accuracy and process control, domestically produced three in one equipment is mainly used in the production of non sterile raw materials.
The centrifugal three in one equipment adds the function of hot air drying on top of the vertical filtration centrifuge, with various forms such as filter bags or metal filter plates. The production process is basically the same as the tank type three in one, except that turning the pumping dry into centrifugal drying can greatly reduce the production time of a single batch of materials. However, due to the volume limitation of the centrifuge silo, the production capacity of a single batch is limited, making it more suitable for the production and use of medium and small batches of sterile raw materials. Due to the fact that this equipment can place the silo and transmission device separately inside and outside the sterile room, there is no need to enter the sterile room for equipment maintenance, making production and use very convenient. In recent years, joint ventures in the domestic API industry have introduced such equipment, and Skeuomorph have also been produced in China.
▲ Spray Dryer is applicable to liquid materials
The drying process of spray dryer is similar to airflow drying. After the initial filtration of the air, it is heated by a heater, and the generated hot air is filtered through several stages (selected according to the drug grade). Then, a uniformly rotating airflow is generated by a hot air distributor in the spiral case channel at the top of the drying chamber and enters the drying chamber. The material is filtered through a centrifugal atomizing disc or pressure nozzle, generating a dispersed and fine material mist. The mist comes into contact with the swirling hot air, causing rapid evaporation of water and drying of the material in a very short time.
This drying equipment is suitable for drying liquid materials with good fluidity, such as solutions, Emulsion, suspensions and pastes. Now this equipment can be used for drying Streptomycin, Gentamicin and various biological extracts in the API industry.
▲ Realization of CIP and SIP in fluidized beds
During the drying process of a fluidized bed, drugs are added from the upper part of the bed, and hot air is blown in from the bottom, passing through a porous distribution plate and in contact with materials with a certain thickness of the material layer. The materials are in a fluidized and boiling state, flipping up and down in the airflow, mixing and colliding with each other. The contact area between gas and solid is large, and intense heat and mass transfer is carried out, greatly improving the drying speed and efficiency. It is an ideal drying equipment. Some wet materials can be dried in one go to achieve the required moisture index. The fluidized boiling state has high thermal efficiency. The residence time can be adjusted, making it easy to obtain low moisture finished products. Large and small particles can be graded on the bed surface, coarse particles can be discharged from the bed, and fine powder can be discharged from the dust collector. For some materials, bag dust removal can be done inside the host (built-in), saving floor space, simple structure, and low investment.
This drying equipment is suitable for drying powder, particle, silk and strip materials. The equipment is fully sealed and can carry out CIP and SIP. It is widely used in the production of antibiotics and Semisynthesis antibiotics in the pharmaceutical industry.
▲ High thermal efficiency of fluidized bed without dead corners
Fluidized beds are divided into ordinary fluidized beds and vibrating fluidized beds, and vibrating fluidized beds are mostly used for drug drying due to the influence of fluidity. The dryer is vibrated by a vibrating motor to generate excitation force, causing the machine to vibrate. The material jumps forward under the excitation force in a given direction. At the same time, hot air is inputted into the bed bottom to keep the material in a fluidized state. The material particles fully contact the hot air, undergoing a fierce heat and mass transfer process. At this time, the thermal efficiency is high. The upper chamber is in a slightly negative pressure state, with wet air being led out by the induced draft fan and dry materials being discharged from the discharge port, thus achieving the ideal drying effect.
The drying equipment has uniform fluidization, no dead angle, uniform temperature distribution and high thermal efficiency. Suitable for drying granular, powder, strip, and filamentous materials, such as starch, glucose, and many pharmaceutical intermediates produced in large quantities can be selected.
▲ Adding a powder mixer to the freeze-drying machine to ensure uniformity
Vacuum freeze flash dryer is suitable for drying thermosensitive or easily oxidizing drugs, commonly known as freeze-drying machine, mainly including freeze-drying box, vacuum system, heating system, refrigeration system, etc. According to the shelf area, it can be divided into small experimental freeze-drying machines, medium production freeze-drying machines, and large industrial production freeze-drying machines. There are many applications of freeze-drying machines for the drying of raw materials and formulations. The main requirements are high reliability, complete sterilization functions, and a temperature difference of no more than 1.5 ℃ between the inner and outer layers of the same shelf. This also requires good flatness of the shelf.
When using this equipment to dry raw materials, it is advisable to add a powder mixer to ensure product uniformity. Ampicillin, large amounts of blood products, artificial culture drugs, antibodies, vaccines, etc. are mostly used with freeze-drying machines.