In recent years, spray drying technology has been widely used in the pharmaceutical industry. In the field of solid preparations, this technology is often used for the drying of highly heat-sensitive drugs and liquids that are easily decomposed during the concentration of feed liquids. In the application process, different drug substances will have different special requirements for spray drying. How to meet these requirements, should pay attention to what details are the concerns of both the device design producer and the user.
Guaranteeing cleanliness requirements The main processes for the production of some APIs need to be performed in a clean environment of 100,000 grades. Spray drying is an important process for quality control. In order to ensure the quality of medicines, the part of the spray dryer that contacts the material must be made of stainless steel. For materials with strong acid corrosion, 316L stainless steel is the best choice. Drying chamber, cyclone separator, filter and other parts that directly contact the material shall have a smooth inner wall, no dead angle, easy to disassemble, and convenient for cleaning.
Due to the huge size of the system, spray dryers cannot be placed in a clean area as a whole, and often only part of the collected material is placed in a clean area. In this case, the system must be well sealed to prevent external contamination of the system.
Avoid sticking phenomenon In the spray drying process of solid preparations (especially traditional Chinese medicine), the sticking wall phenomenon is a prominent problem that hinders the normal operation of the spray dryer. The sticky wall of the material is not only unfavorable for the collection operation, but with the prolongation of time, the sensitive sticky wall material will degenerate into a substandard material. From the point of view of the process, the means of solution include the selection of suitable solvents, the addition of auxiliary materials, and the modification of process parameters. However, there is not much room for adjustment of these methods, so a fundamental solution must be sought from the perspective of equipment.
In recent years, experts at home and abroad have studied the problems of sticking and agglomeration in the drying process. They believe that the main cause of sticking is the wall temperature, which summarizes five measures to prevent sticking: the use of a sandwich drying tower, By air cooling, the wall temperature is kept below 50°C; through the tower wall, the cyclone gas sheet is tangentially introduced into the secondary air cooling tower wall; an air broom consisting of a row of nozzles is installed on the near wall of the tower and is placed along the tower wall. Slow rotation; increase the air hammer on the tower wall, forcibly detach the sticky wall material by hammering; increase the precision of processing, and polish the inner wall of the tower to reduce sticking.
Improved self-control performance Spray drying is a continuous production process. The control points of the closed-cycle system include: feed concentration, feed rate, inlet air speed, inlet air temperature, system pressure, differential pressure of various components, gas purity detection, etc. The manual adjustment is very difficult, so you must strengthen the system's self-control. A good set of automatic control system can make the entire spray drying system run smoothly, reduce the rate of product failure, and reduce potential safety hazards.
Meet the requirements of different physical properties After the drug substance has been spray-dried, the preparation process must be further completed. Therefore, in order to improve the effect of the formulation and the absorption and absorption of the final drug, different production requirements will impose different requirements on the physical properties of the spray-dried product. The dispensing of drugs generally controls the volume in accordance with the volume, which requires that the product's bulk density is stable and the product's fluidity is better, while oral granules often require instant solubility. By varying the degree of atomization or changing the operating conditions appropriately to control the drying rate, products with different bulk densities can be produced, but the extent of change is limited.
At present, there is a new technology in improving physical properties - foam spray drying, that is, the feed liquid is foamed before spray drying. This method was originally proposed for improving thermal efficiency and was later used to adjust the physical properties of the product. It has been proved that the product obtained by foam spray drying has large particle size, porosity, multiple depressions, rough surface and good instant solubility.
In addition, there are some special requirements for oral drug substances, such as the shape of particles. Production practice has proved that different shapes of particles can be obtained by changing the atomization method.
The safety protection measures are indispensable The particularity of certain drugs will also put forward higher requirements for the protection design of the equipment. The materials that are dissolved with organic solvents must have the explosion-proof requirements for the entire system during drying. At the same time, explosion-proof models must be selected when designing accessories such as motors, meters, and control valves. In addition, in order to prevent the mixture of solvent and air into explosive gas, the system must adopt a closed-cycle system, and the carrier should use inert gas such as nitrogen. In addition, the drying of some oxidizing materials also requires the use of a nitrogen-based closed circulation system.
Environmental indicators must be met Spray-dried products are fine particles that are prone to dust formation. In order to meet the requirements of environmental protection, it is not enough to use only conventional cyclone separators to separate products and purify exhaust gas. It is also possible to use bag filter to purify the exhaust gas so that the dust content of exhaust gas is less than 50 mg/cubic nanometer to meet the standards. Or use a wet scrubber to reduce the tail gas dust to 15-35 mg/cubic nanometer. When nitrogen is used as a carrier, the system must be closed and the exhaust vented outdoors.
Increasing the heat utilization rate is a top priority. The inlet temperature of hot air is 250°C to 500°C in parallel operation, 200°C to 300°C in countercurrent operation, and the outlet temperature is generally controlled at 60°C to 100°C after atomization and drying. The lower rate is also a deficiency of spray drying.
At present, domestic industrial-scale spray dryers generally have a thermal efficiency of 30% to 50%. With foreign spray dryers with waste heat recovery, the thermal efficiency can reach 70%, but the equipment only has economic significance if the production capacity is greater than 100 kg (water)/hour. However, when a nitrogen carrier and organic solvent are used, a closed circulation system can be used to recycle nitrogen and condense the solvent, which can effectively reduce the production cost.
However, in general, the cost of the spray drying process needs further study by equipment designers and producers to find better countermeasures to reduce costs.
Guaranteeing cleanliness requirements The main processes for the production of some APIs need to be performed in a clean environment of 100,000 grades. Spray drying is an important process for quality control. In order to ensure the quality of medicines, the part of the spray dryer that contacts the material must be made of stainless steel. For materials with strong acid corrosion, 316L stainless steel is the best choice. Drying chamber, cyclone separator, filter and other parts that directly contact the material shall have a smooth inner wall, no dead angle, easy to disassemble, and convenient for cleaning.
Due to the huge size of the system, spray dryers cannot be placed in a clean area as a whole, and often only part of the collected material is placed in a clean area. In this case, the system must be well sealed to prevent external contamination of the system.
Avoid sticking phenomenon In the spray drying process of solid preparations (especially traditional Chinese medicine), the sticking wall phenomenon is a prominent problem that hinders the normal operation of the spray dryer. The sticky wall of the material is not only unfavorable for the collection operation, but with the prolongation of time, the sensitive sticky wall material will degenerate into a substandard material. From the point of view of the process, the means of solution include the selection of suitable solvents, the addition of auxiliary materials, and the modification of process parameters. However, there is not much room for adjustment of these methods, so a fundamental solution must be sought from the perspective of equipment.
In recent years, experts at home and abroad have studied the problems of sticking and agglomeration in the drying process. They believe that the main cause of sticking is the wall temperature, which summarizes five measures to prevent sticking: the use of a sandwich drying tower, By air cooling, the wall temperature is kept below 50°C; through the tower wall, the cyclone gas sheet is tangentially introduced into the secondary air cooling tower wall; an air broom consisting of a row of nozzles is installed on the near wall of the tower and is placed along the tower wall. Slow rotation; increase the air hammer on the tower wall, forcibly detach the sticky wall material by hammering; increase the precision of processing, and polish the inner wall of the tower to reduce sticking.
Improved self-control performance Spray drying is a continuous production process. The control points of the closed-cycle system include: feed concentration, feed rate, inlet air speed, inlet air temperature, system pressure, differential pressure of various components, gas purity detection, etc. The manual adjustment is very difficult, so you must strengthen the system's self-control. A good set of automatic control system can make the entire spray drying system run smoothly, reduce the rate of product failure, and reduce potential safety hazards.
Meet the requirements of different physical properties After the drug substance has been spray-dried, the preparation process must be further completed. Therefore, in order to improve the effect of the formulation and the absorption and absorption of the final drug, different production requirements will impose different requirements on the physical properties of the spray-dried product. The dispensing of drugs generally controls the volume in accordance with the volume, which requires that the product's bulk density is stable and the product's fluidity is better, while oral granules often require instant solubility. By varying the degree of atomization or changing the operating conditions appropriately to control the drying rate, products with different bulk densities can be produced, but the extent of change is limited.
At present, there is a new technology in improving physical properties - foam spray drying, that is, the feed liquid is foamed before spray drying. This method was originally proposed for improving thermal efficiency and was later used to adjust the physical properties of the product. It has been proved that the product obtained by foam spray drying has large particle size, porosity, multiple depressions, rough surface and good instant solubility.
In addition, there are some special requirements for oral drug substances, such as the shape of particles. Production practice has proved that different shapes of particles can be obtained by changing the atomization method.
The safety protection measures are indispensable The particularity of certain drugs will also put forward higher requirements for the protection design of the equipment. The materials that are dissolved with organic solvents must have the explosion-proof requirements for the entire system during drying. At the same time, explosion-proof models must be selected when designing accessories such as motors, meters, and control valves. In addition, in order to prevent the mixture of solvent and air into explosive gas, the system must adopt a closed-cycle system, and the carrier should use inert gas such as nitrogen. In addition, the drying of some oxidizing materials also requires the use of a nitrogen-based closed circulation system.
Environmental indicators must be met Spray-dried products are fine particles that are prone to dust formation. In order to meet the requirements of environmental protection, it is not enough to use only conventional cyclone separators to separate products and purify exhaust gas. It is also possible to use bag filter to purify the exhaust gas so that the dust content of exhaust gas is less than 50 mg/cubic nanometer to meet the standards. Or use a wet scrubber to reduce the tail gas dust to 15-35 mg/cubic nanometer. When nitrogen is used as a carrier, the system must be closed and the exhaust vented outdoors.
Increasing the heat utilization rate is a top priority. The inlet temperature of hot air is 250°C to 500°C in parallel operation, 200°C to 300°C in countercurrent operation, and the outlet temperature is generally controlled at 60°C to 100°C after atomization and drying. The lower rate is also a deficiency of spray drying.
At present, domestic industrial-scale spray dryers generally have a thermal efficiency of 30% to 50%. With foreign spray dryers with waste heat recovery, the thermal efficiency can reach 70%, but the equipment only has economic significance if the production capacity is greater than 100 kg (water)/hour. However, when a nitrogen carrier and organic solvent are used, a closed circulation system can be used to recycle nitrogen and condense the solvent, which can effectively reduce the production cost.
However, in general, the cost of the spray drying process needs further study by equipment designers and producers to find better countermeasures to reduce costs.