According to the basic theory of sublimation stage and eutectic point, the freeze drying process of the freeze dryer can be divided into three stages: pre-freezing, sublimation drying and analytical drying.
1 pre-freeze
In the freeze-drying process, the dried material must first be pre-frozen. So that the moisture in it is in a solid state. Appropriate pre-freezing temperature is an important condition to ensure the freeze-drying effect and product quality. If the pre-freezing temperature does not reach below the eutectic point, the material may not be completely frozen, and will expand and foam or shrink, solute transfer and other irreversible phenomena during sublimation; if the pre-freezing temperature is too low, it will not only increase the freezing energy consumption, but also It will also reduce the activity of biopharmaceuticals. Generally, the temperature of the material is reduced to 10-15℃ below the eutectic point during pre-freezing, and then kept for a period of time (about 1-2h) to overcome the supercooling phenomenon of the solution. The material is completely frozen.
In addition, the pre-freezing speed also affects the performance of freeze-dried products. Rapid freezing will form small ice crystals, the gaps between the crystal lattices are small, and the water vapor is not easily discharged during sublimation, which reduces the sublimation rate, but the product particles are fine and have a larger ratio
surface area. The resilience of the product is better. On the contrary, slow freezing will form larger ice crystals, which is beneficial to increase the rate of sublimation and dry bath, but the recovery of freeze-dried products is poor and the dissolution performance is reduced. Therefore, an appropriate pre-freezing speed must be selected during the freeze-drying operation.
2. Sublimation and drying
Sublimation drying is the first stage of freeze drying. Place the pre-frozen materials in a closed vacuum dryer, heating and depressurizing, and the moisture content is directly sublimated from the solid phase to the gas phase. The materials are decontaminated to achieve the purpose of drying, and the gas phase generated by sublimation is introduced into the condenser It is cured and removed.
Because the moisture sublimation requires heat, such as lg ice completely sublimates to water vapor, it needs to absorb about 2800J of heat, so the material must be heated. If the heating is not enough, the sublimation drying can be carried out by reducing the pressure, but the sublimation reduces the temperature of the material itself, which in turn causes the sublimation rate to decrease, the freeze-drying time is prolonged, and the production efficiency decreases. If the material is heated too much, in addition to the heat required for the sublimation process, the remaining heat will increase the temperature of the material. When it reaches or exceeds the eutectic temperature, it may cause partial melting, or even melt the material completely, causing it to dry. The material shrinks and foams, etc.,
The freeze-drying operation failed. Therefore, during the entire sublimation drying stage, the temperature of the material must be controlled below the eutectic point, that is, the material must be kept in a frozen state.
After sublimation drying has been carried out for a period of time, most of the ice crystals have been sublimated into steam. The first stage of drying is completed. This process can remove about 90% of all moisture.
3Analysis and drying
Use a higher vacuum and a higher temperature for 2-3 hours to remove the remaining adsorbed moisture in the sublimation stage, that is, the second stage drying, which is called analytical drying. After analysis and drying, the residual moisture in the material can be reduced to less than 0.5%-3% until it reaches the drying requirement.