Spray drying technology in the production of solid preparations

The spray drying technology uses a spray method to disperse the material in a hot air stream in a mist state. The material is in full contact with the hot gas to complete the heat transfer and mass transfer process in an instant, so that the solvent is quickly evaporated into a gas to achieve the purpose of drying. . Spray drying technology is widely used in the pharmaceutical industry. In the field of solid preparations, it is often used for the drying of easily decomposable drugs in high heat sensitive medicines and liquid concentrates. The obtained product has fine particle size, uniformity, good fluidity and fast solubility.

Spray dryer features and classification

The spray dryer is a drying device for directly drying a solution or a suspension into solid particles, which can save unit operations such as evaporation, crystallization, separation and pulverization, and can be continuously and automatically produced, and the operation is stable. By adopting the drying method, the gas-solid two-phase contact surface area in the spray dryer is large, and the drying time is short, generally 5 to 30 s, which is suitable for drying the heat sensitive material. The product obtained by drying has good performance, and particles of 30 to 50 mm can be obtained, and the product has good fluidity and fast solubility. The disadvantage is that the dryer has a large volume and a low heat transfer coefficient, resulting in low thermal efficiency and high power consumption.

There are many classification methods for spray dryers. According to the flow direction of gas and liquid, it can be divided into parallel flow, counter flow and mixed flow; according to the installation method of atomizer, it can be divided into upper spray type and lower spray type; The structure can be divided into centrifugal type, pressure type and air flow type; according to whether the heating gas is circulated, it can be divided into open type, partial circulation type and closed type.

Basic process of spray drying (closed)

The liquid is atomized by the atomizer and dispersed into fine mist droplets into the drying chamber. At the same time, the heating gas is sent to the heater through the blower to heat up, and then enters the drying chamber. The liquid droplets are thoroughly mixed and contacted with the hot gas in the drying chamber. The droplets evaporate instantaneously into a gas, and the material is dried into fine particles. The mixed gas-solid two-phase is separated into the cyclone by the induced draft fan, and the solid material is settled to the bottom collector, and the gas phase is led to the dust filter to capture the escaped material. After the filtered gas phase is condensed by the condenser, the carried solvent becomes a liquid, which can be collected and used, and the gas as a carrier is dried and recycled in the system. The flow chart is as follows:

Process requirements for solid preparations

There are many kinds of solid preparations, and the process requirements are also very different. In the process of designing and manufacturing the spray dryer, it is better to make different designs for different varieties to achieve the best condition of equipment and process. Spray dryers for the production of solid preparations should meet the following requirements:

Cleanliness requirements

The main process of API production needs to be carried out in a clean environment of 100,000 grades. Spray drying is an important process of quality control. The part of the spray dryer that contacts the material should be made of stainless steel. For materials with strong acid corrosion, 316L stainless steel is the best choice. The parts that directly contact the material such as the drying chamber, the cyclone separator, and the filter should be smooth inside the wall, have no dead angle, and are easy to disassemble for easy cleaning. Spray dryers tend to be bulky, so they cannot be placed in a clean area as a whole, and often only the part where the material is collected is placed in a clean area, which requires good system sealing performance to prevent external contamination of the system.

Avoid sticking

The sticking phenomenon is a prominent problem that hinders the normal operation of the spray dryer, and the spray drying process of the solid preparation (especially the traditional Chinese medicine) is particularly obvious. The sticky wall of the material is not only unfavorable for the collection operation, but as time goes on, the sensitive sticky wall material will deteriorate into a non-conforming material. From a process point of view, the solution includes selecting the right solvent, adding the excipients, and changing the process parameters. However, there is not much room for adjustment of these methods, so a fundamental solution must be sought from the perspective of the equipment. Experts at home and abroad have studied the problem of sticking and agglomeration during the drying process. It is believed that the main cause of sticking is the wall temperature.

Here are five possible ways to prevent sticking:

The wall drying tower is used, and air cooling is performed therebetween to keep the wall temperature below 50 ° C;

Introducing a secondary air cooling tower wall tangentially through the tower wall cyclone;

An air broom consisting of a row of nozzles is installed near the wall of the tower and is slowly rotated along the wall of the tower;

The tower wall increases the air hammer, and the sticking of the air hammer forces the viscous material to be detached;

Increasing the precision of the machining, the inner wall polishing of the tower can also reduce the sticking wall.

Self-control performance

Spray drying is a continuous production process. The control points of the closed circulation system include: feed concentration, feed rate, inlet speed, inlet air temperature, system pressure, differential pressure of each component, gas purity detection, etc., relying on traditional manual adjustment. very difficult. A good automatic control system can make the whole spray drying system run smoothly, reduce the product's failure rate and reduce safety hazards.

Drying effect

The drug substance also needs to further complete the preparation process, and different requirements are imposed on the physical properties of the spray-dried product in terms of improving the effect of the preparation and the absorption effect of the final drug. First of all, the moisture content is the first indicator of dry products and should be controlled within a certain range. Secondly, the dispensing of drugs generally controls the volume according to the volume, which requires that the bulk density of the product is stable and the fluidity of the product is good. Oral granules often require fast solubility. By varying the dispersion of the atomization or by appropriately changing the operating conditions to control the drying rate, products having different bulk densities can be produced, but the magnitude of the variation is limited. One technique worth mentioning in improving physical properties is foam spray drying, in which the feed liquid is first foamed and then spray dried. The method was originally proposed to improve thermal efficiency and was later used to adjust the physical properties of the product. It has been proved that the product prepared by foam spray drying has large particle size, is porous, has many depressions, has a rough surface, and has good fast solubility. In addition, there are some special requirements for oral drug substances, such as particle shape. Generally, particles of different shapes can be obtained by changing the atomization method. Before selecting a spray dryer, it is best to carry out a parameter optimization experiment with the assistance of the equipment manufacturer to determine the optimal combination of parameters to ensure the drying effect of the sprayed medicine.

Safeguard

The particularity of the drug also puts higher demands on the protection design of the device. Materials dissolved in organic solvents require that the entire system must meet explosion protection requirements when dry. Explosion-proof type should be selected when designing motors, instruments, control valves and other accessories. In addition, in order to prevent the solvent and air from mixing into an explosive gas, the system must use a closed circulation system, and the carrier should use an inert gas such as nitrogen. In addition, some of the easy-to-oxide materials are dried, and a closed circulation system using nitrogen as a carrier is also used.

Environmental protection

Spray-dried products are fine particles. In order to meet the requirements of environmental protection, it is not enough to separate the products with cyclone separator and purify the exhaust gas. Generally, it is also purified by bag filter to make the exhaust gas content less than 50mg/nm3; Or use a wet scrubber to reduce the dust content of the exhaust gas to 15 ~ 35mg / nm3 gas. When using nitrogen as the carrier, the system should be sealed and the exhaust port should be led to the outside.

cut costs

The hot air inlet temperature is 250 to 500 ° C in the cocurrent operation and 200 to 300 ° C in the countercurrent operation, and the outlet temperature is generally controlled at 60 to 100 ° C after the atomization drying. Spray drying has a low heat utilization rate, and industrial scale spray dryers generally have a thermal efficiency of 30% to 50%. Foreign spray dryers with waste heat recovery can achieve a thermal efficiency of 70%, but the equipment is only economically meaningful when the production capacity is greater than 100kg (water) / h. However, when a nitrogen carrier and an organic solvent are used, a closed circulation system can be used, and the nitrogen can be recycled, and the solvent can be condensed, thereby effectively reducing the production cost.