We will inevitably encounter some problems related to the lyophilized samples of the lyophilizer. We will discuss them through several phenomena:
1、 After freeze-drying stratification, the lower layer shrinks
Phenomenon: after freeze-drying stratification, the lower layer shrinks or the whole product shrinks. Some products are frozen well, and some shrink into few almost empty bottles.
Analysis: not pre frozen, sublimation is too fast. It may be that the local temperature or pressure of the lyophilizer is too high, resulting in local melting.
1. If the drug solute is relatively small, such problems are more likely to occur.
2. Whether the rubber plug of the shrinking product is well sealed. On the contrary, if the product is easy to absorb moisture, this phenomenon will also occur.
The materials at the lower part are not completely dry, and the ice cubes in the supporting materials fuse and collapse after being taken out of the warehouse; The material is heated too fast and too early after entering the warehouse, the eutectic point of the material is not reached, and the bottom layer of the material is boiling.
The temperature rises rapidly, and the water does not take off, causing the lower part to melt.
The glass transition temperature of drugs is low.
The freezing technology used by the freeze dryer takes a certain time. During this freezing time, some slightly soluble substances crystallize and precipitate in the lower layer of the material, resulting in different results between the upper layer and the lower layer after the material is frozen. In this regard, the sublimation temperature can be reduced once and the sublimation time can be prolonged.
2、 Freeze dried surface peeling
Phenomenon: when vacuumizing, there are many small bubbles on the surface, and one layer of the surface is separated after freeze-drying.
Analysis: the material surface has been partially thawed before the vacuum degree of the lyophilizer meets the requirements. The pre freezing is not good, the water is not completely frozen, and the water overflows to form bubbles during vacuum pumping.
This phenomenon is mostly caused by the migration of salt to the surface of freeze-dried samples. Pre freezing can be strengthened.
For the change of the pressure of the front box during primary drying, because the vacuum affects the sublimation speed, you can first check the freeze-drying record data to see if there is any abnormal fluctuation in the pressure of the front box and the product temperature. In addition, you can confirm the position of the layered bottles. The bottles around the plate will sublimate faster than the bottles in the middle.
There is no difference between the changes of vacuum before and after comparison.
Vacuum control is mainly dominated by heat supply. The performance of vacuum pump, the cleanliness of oil and the temperature of water trap are important factors.
In addition, delamination will occur after a long time. It is normal to control the freeze-drying time. For example, the temperature difference between the center of the plate layer and the edge of the product is 4-7 degrees (a large amount of freeze-drying). During freeze-drying, the one-time freeze-drying time should be longer.
