Brief introduction of freezing process of vacuum freeze dryer in laboratory

Freeze drying is a technology of drying by using the principle of sublimation It is a process of rapidly freezing the dried material at low temperature, and then sublimating the frozen water molecules directly into water vapor escaping under appropriate vacuum environment The product obtained by freeze drying is called lyophilizer, which is called lyophilization When the frozen solution of a product is frozen rapidly (cooling at 10-50 ℃ per minute), the grain size remains visible under the microscope; on the contrary, when it is frozen slowly (1 ℃ / min), the crystal formed is visible to the naked eye The larger space left by the coarse crystal in sublimation can improve the efficiency of freeze-drying The smaller space left by the fine crystal after sublimation can hinder the sublimation of the lower layer The quick-frozen finished product has fine particles, uniform appearance, large specific surface area, good porous structure, fast dissolution speed, and relatively stronger moisture absorption of the finished product Drugs are pre frozen in two ways in the freeze-drying machine: one is to cool down the product and the drying oven at the same time; the other is to cool down the shelf of the drying oven to about - 40 ℃, and then put the product into it The former is equivalent to slow freezing, while the latter is between quick freezing and slow freezing, so it is often used to give consideration to the freeze-drying efficiency and product quality The disadvantage of this method is that when the product is put into the tank, the water vapor in the air will quickly condense on the shelf At the initial stage of sublimation, if the temperature of the board rises rapidly, the sublimation of large area may exceed the normal load of the condenser This phenomenon is particularly significant in summer The product is frozen in a static state Experience has proved that supercooling is easy to occur until the product temperature has reached the eutectic point However, the solute still does not crystallize In order to overcome the supercooling, the freezing temperature of the product should be lower than a range below the eutectic point, and it should be kept for a period of time until the product is completely frozen The second sublimation condition and speed: when the saturated vapor pressure of ice at a certain temperature is greater than the partial pressure of water vapor in the environment, the sublimation can start; when the condenser with lower temperature than the product has the function of suction and capture of water vapor, it is the necessary condition for maintaining the rise The distance between two successive collisions is called the mean free path, which is inversely proportional to the pressure At atmospheric pressure, the value is very small, the sublimated water molecules are easy to collide with the gas and return to the surface of the steam source, so the sublimation speed is very slow With the decrease of pressure below 13.3pa, the average free path increases 105 times, which makes the sublimation speed significantly faster, and the water molecules flying out seldom change their own aspects, thus forming a directional steam flow The vacuum pump plays a role of pumping out long-term gas in the freeze dryer to maintain the necessary low pressure for sublimation It is impossible for ordinary vacuum pump to pump out such a large volume in unit time The condenser actually forms a vacuum pump for collecting water vapor The temperature of products and condensation is usually - 25 ℃ and - 50 ℃ The saturated vapor pressure of ice at this temperature is 63.3pa and 1.1pa respectively, so there is a considerable pressure difference between the sublimation surface and the condensation surface If the partial pressure of the non condensable gas in the system can be ignored at this time, it will promote the water vapor sublimated from the products to reach the surface of the condenser at a certain flow rate and form ice frost The sublimation heat of ice is about 2822j / g if the sublimation process does not supply heat, then the end product can only reduce the internal energy to compensate the sublimation heat, until its temperature and the condenser temperature balance, the sublimation will stop In order to keep the temperature difference between sublimation and condensation, it is necessary to provide enough heat for the products During the three sublimation process, the temperature of the product is lower than the eutectic point Therefore, the shelf temperature should be controlled If the product has been partially dried, but the temperature exceeds its eutectic point, the product will melt At this time, the molten liquid will saturate the ice, but not the solute Therefore, the dried solute will dissolve rapidly After Zui, it will condense into a thin rigid block, with extremely poor appearance and poor dissolution rate If the melting of the product occurs in a large scale In the later stage of sublimation, because the amount of molten liquid is less, it is absorbed by the dry porous solid, resulting in the defect of the block after freeze-drying, and the slow dissolution rate can still be found when water is added for dissolution In a large number of sublimation processes, although there is a great difference between the shelf and the product temperature, the plate temperature, the condenser temperature and the vacuum temperature are basically unchanged, so the sublimation heat absorption is relatively stable, and the product temperature is relatively constant As the products are dried from top to bottom, the resistance of ice sublimation increases gradually The temperature of the product will rise slightly correspondingly Until no ice crystals exist with the naked eye At this time, more than 90% of the moisture has been removed So far, the process of large-scale sublimation has basically ended In order to ensure the completion of large-scale sublimation of the whole box of products, the plate temperature still needs to maintain a stage before the second stage of heating The remaining percentage of water is called residual water, which is different from free state water in physicochemical properties Residual water includes chemically combined water and physically combined water, such as combined crystal water crystallization, protein water bound by hydrogen bond and adsorbed water on solid surface or capillary, etc As the residual water is bound by a certain gravity, its saturated vapor pressure is reduced to some extent, so the drying speed is obviously reduced Although increasing the product temperature can promote the gasification of residual water, if the temperature exceeds a certain limit, the biological activity may also decline sharply The high drying temperature of Zui to ensure the safety of products should be determined by experiments In the second stage, we usually keep the plate temperature about 30 ℃ and keep it constant At the beginning of this stage, due to the increase of plate temperature, the residual water is less and it is not easy to gasify, so the temperature of the product rises faster However, as the product temperature and plate temperature gradually close, the heat transfer becomes more slow, and it needs to wait for quite a long time Practical experience shows that the drying time of residual water is almost the same as that of a large amount of sublimation, sometimes even more than that The four freeze-drying curve can be obtained by recording the change of shelf temperature and product temperature with time According to the typical freeze-drying curve, the shelf temperature is divided into two stages The shelf temperature is kept low when a large number of sublimation occurs According to the actual situation, it can be generally controlled between - 10 and 10 In the second stage, the shelf temperature should be raised properly according to the product properties This method is suitable for products with low melting point If the performance of the product is not clear, the performance of the machine is poor or its work is not stable, this method is also more stable If the eutectic point of the product is high, the vacuum degree of the system can also be maintained well, and the refrigerating capacity of the condenser is sufficient, a certain heating speed can also be used to raise the shelf temperature to the allowable high temperature of Zui until the end of freeze-drying, but it is also necessary to ensure that the temperature of the product during a large amount of sublimation shall not exceed the eutectic point If the product is unstable to heat, the plate temperature in the second stage should not be too high In order to improve the sublimation speed of the stage, the shelf temperature can be raised to above the allowed Zui high temperature of the product at one time; when a large number of sublimation stages are basically over, the plate temperature can be reduced to the allowed Zui high temperature, although the latter two ways can improve a lot of sublimation speed, their anti-interference ability will be reduced correspondingly, and sudden decrease of vacuum degree and refrigeration ability or power failure may be possible It will melt the product At present, it is still a common way to master the methods reasonably and flexibly