In short: Bo Yikang has been committed to the development of freeze drying technology. In the process of long-term customer service, it was found that the majority of freeze dryers use customers to understand the mechanism of freeze-drying, and how to explore and optimize the freeze-drying process of products should not be known. In order to solve the above problems, we will collect and freeze the technical data to help users who are using lyophilization or are planning to use lyophilization for dry preservation. Freeze vacuum drying (hereinafter referred to as lyophilization) is a stabilized material drying process. It is a method in which a water-containing substance is first frozen into a solid state, and then the water therein is directly sublimated from a solid state to a gaseous state to remove the water and preserve the substance. After the product in solution state is subjected to sublimation and desorption, the solvent in the product is reduced to a certain extent, thereby preventing the formation of microorganisms or the chemical reaction between the solute and the solvent, so that the product can be preserved for a long time and maintained. The nature. Water and solution properties Water has three states, solid, liquid, and gaseous. The three states can be transformed into each other. Corresponding to all processes below 0 °C and 610Pa, as long as certain conditions are met, it can become a sublimation process. The substance has three states: solid, liquid and vapor. The state of matter is related to its temperature and pressure. As shown in the figure, the state balance diagram of water (H2O). The three curves OA, OB, and OC in the figure represent the relationship between pressure and temperature when ice and water, water and water vapor, ice and water vapor coexist. They are called melting line, boiling line and sublimation line. The three curves divide the surface into three regions, I, II, and III, which are called solid phase zone, liquid phase zone, and gas phase zone. Arrows 1, 2, and 3 respectively indicate the process of melting ice into water, vaporizing into water vapor, and sublimating into water vapor. The top of the curve OB has a point K with a temperature of 374 °C, called the critical point. If the temperature of the water vapor is higher than its critical temperature of 374 °C, the water vapor cannot become water no matter how much the pressure is increased. The intersection point O of the three-curve is a state in which the solid, liquid, and vapor phases coexist, and is called a triple point, and the temperature is 0.01 ° C and the pressure is 610 Pa. Below the triple point, there is no liquid phase. If the pressure on the ice surface is kept below 610 Pa and the ice is heated, the ice will directly turn into the gas phase without passing through the liquid phase. This process is called sublimation. Freeze drying process of solution Xmas Gummy Candy,Christmas Gummies,Christmas Gummy Candy,Fruity Christmas Candy Montreal Shantou Food Co., Ltd , https://www.montrealsnack.com
Vacuum freeze-drying is a process from liquid to solid to gaseous. During the lyophilization process, the "liquid bridge" between the solute particles has been frozen into a "solid bridge", the relative position between the two particles has been fixed, and there is no surface tension between the two particles at the gas-liquid interface. As the solvent continues to sublimate, the "fixed bridge" continues to decrease, but the relative position between the two particles no longer changes until the "solid bridge" disappears completely.
The lyophilized solution is typically configured to contain a dilute solution of 4% to 25% of the solid material. The composition of the water in the solution:
1. Most of the water is free water that is present in solution in the form of water molecules.
2. A small portion is bound water adsorbed in the lattice gap of the solid matter or bonded to some polar gene clusters by hydrogen bonding.
3. Water that is fixed in organisms and cells is mostly free water that can be frozen and sublimated. It also contains some bound water that cannot be frozen and is difficult to remove.
The purpose of lyophilization is to remove free water in the material and a portion of the adsorbed water adsorbed in the gap of the solid lattice in a low temperature, vacuum environment. The freeze-drying process is divided into the following steps:
Pre-freezing: Pre-freezing is to solidify the free water in the solution, giving the dried product the same form as before drying, preventing irreversible changes such as foaming, concentration, shrinkage and solute movement during evacuation and drying.
During the freezing process, the solution needs to be cooled to below the freezing point. After the nucleus is generated, the free water begins to crystallize in the form of pure ice, and the heat of crystallization is released to raise the temperature to the freezing point. As the crystal grows, the solution concentration Increasing, when the concentration reaches the eutectic concentration and the temperature drops below the eutectic point, the solution freezes completely.
The faster the cooling rate, the lower the subcooling temperature, the more the number of crystal nuclei formed, the more the crystals are frozen before they grow, and the more crystal grains are formed, the finer the crystal grains. The cooling rate is slow, and the smaller the number of crystal grains formed, the larger the crystal grains. Freeze-dried products must be frozen to a certain temperature before sublimation. This temperature should be set at about 10 to 20 °C below the eutectic point of the product. If the vacuum is not pre-frozen, when the pressure drops to a certain level, the liquid will be Take it away. This kind of situation is also called evaporation. This kind of steam is called unsaturated steam. If the product freezes and is vacuumed, the gas in the liquid will quickly escape and cause "boiling". If the product is frozen in "boiling", some of it may escape from the bottle, causing drug loss or unevenness of the surface of the product. It can be seen that the temperature of the eutectic point is the safest temperature to ensure the normal drying of the product, and can only be lower than it, and cannot be higher than the co-melting point temperature.
Sublimation drying (drying once)
The frozen product is heated in a closed vacuum vessel, and the ice crystals are sublimated into water vapor to escape and the product is dehydrated and dried. The drying is gradually moved inward from the outer surface, and the residual space after the ice crystals sublimate becomes the escape passage of the sublimated water vapor. The heat required for sublimation is obtained by several ways: conduction of solids, radiation, and convection of gases.
Product sublimation is limited by the following temperatures:
The temperature of the frozen portion of the product should be lower than the temperature at the point of co-melting of the product. The temperature of the dry portion of the product is below its disintegration temperature or the maximum temperature allowed (no scorch or variability). Maximum shelf temperature.
Analytical drying (secondary drying)
The first stage of drying is to remove water in the form of ice crystals, so the temperature and pressure must be controlled below the co-melting point of the product so that the ice crystals are not melted. For adsorbed water, because of its high adsorption energy, if it does not provide enough energy, water cannot be resolved from adsorption. In order to allow the analyzed water vapor to have sufficient driving force to escape the product, a large vapor pressure difference must be formed inside and outside the product, so that a high vacuum is maintained in the tank. After the second stage of drying, the residual moisture content of the product can generally be controlled between 0.4% and 4%.