The material into the freeze-drying box began to freeze.
Freeze-dried materials is the most important parameters in the process of temperature and freeze the pressure in the cabinet.
The temperature of the freeze-drying curve is in the process of freeze-drying boring, the curve of the pressure changes over time change over time.
In the practice of freeze-drying curve commonly used clapboard temperature (
Or the space temperature in the cabinet)
Relations with time curve.
Main parameters for monitoring the lyophilization process, general and freeze drying machine can automatically record clapboard temperature, material temperature, water vapour condenser parameters such as temperature, freeze-drying box pressure and the relation curve of the time.
the freeze-drying curve shape and what's the capacity of product performance, and types of packaging containers, equipment conditions, many factors are related.
Even the same product, the manufacturer is different, freeze-drying curve is exactly the same.
Production should be based on each part of the main parameters of freeze-drying process is as follows.
A precool temperature
precool temperature must be lower than the material of the eutectic point (
Melting point)
The temperature of 5 -
10℃。
Each eutectic point temperature of the material to measure, usually by eutectic point temperature in - biological material
Around 30 ℃.
Two precool time
material freezing process is a exothermic process, need a certain amount of time, meet the precool temperature, also need to keep a certain amount of time.
In order to make the whole case all frozen, generally after reaches the precool temperature, it will take about 2 h.
Three precool rate
slow freezing ice crystals is bigger, produced by the rapid freezing of a smaller ice crystals for biological cells, slow cooling effect on life size is large, rapid cooling effect is small.
Between freezing point and eutectic point temperature of the material also need quick cold, otherwise easy to make protein denaturation, life and death is called the effect of the solute.
When frozen after the formation of ice crystals size affect the drying rate and drying the solubility of the products.
Large ice crystals to sublimation, but after drying dissolve slowly, small ice crystals sublimation slow, fast drying after dissolved, can reflect the original structure of the product.
as a result, the need to experiment a suitable cooling rate, make the material has high survival rate, good physical and solubility, and conducive to the sublimation drying process.
the temperature of the four sublimation stage
the biochemical processes of material is an endothermic process, 1 g ice into 1 g steam about 2803 j of heat, so must to material in the process of sublimation temperature cannot exceed the eutectic point temperature, if the material temperature below the eutectic point too much during the process of sublimation, the sublimation rate is reduced, the time needed for sublimation stage increases;
If the material temperature higher than the temperature of the eutectic point, the material melt shrinkage phenomenon will happen, so to control the material temperature is close to eutectic point temperature, but below the eutectic point temperature.
five sublimation stage of clapboard temperature
heat sublimation materials from the diaphragm, control the temperature of the baffle plate can thus achieve the purpose of control the temperature of the material.
Clapboard temperature is according to the material temperature, freeze-drying box pressure and the temperature of the condenser.
If the sublimation process, the temperature of the material below the eutectic point rating and disintegrating temperature, freeze-drying box pressure is lower than the vacuum alarm rules, the condenser temperature is below -
40 ℃, the partition area can continue to rise.
If after clapboard temperature increases to a certain extent, the material temperature is close to the temperature of the eutectic point or collapse point temperature, the pressure in the cabinet or lyophilization is close to alarm rules of stress, or the temperature of the condenser back to -
More than 40 ℃, the baffle heater shall not continue to rise again.
6 sublimation stage pressure
sublimation period of freeze-drying box pressure should be controlled within a certain range.
Pressure is too low, adverse to the heat transfer, when pressure is below 10 pa, gas to spread heat effect, can be neglected;
And when the pressure is higher than 10 pa, gas convection heat transfer increases obviously.
Under same clapboard temperature, the pressure is higher than 10 pa, when the material is easy to get heat sublimation rate is higher.
When the pressure is too high, material mass transfer rate is reduced, slow sublimation, consume fewer calories, temperature of material itself, once the temperature above the eutectic point, partial melting materials.
Freeze-dried biological products strict quality requirements, the appropriate pressure lower, generally in 10 -
It is advisable to 30 pa.
