What are the reasons for the foaming phenomenon in the freeze-drying process of drugs?

What are the reasons for the foaming phenomenon in the freeze-drying process of drugs?
In the process of using the pharmaceutical freeze dryer, due to the different characteristics of different products, it is inevitable to encounter different freeze-drying problems during the operation. Next, we will discuss with you the foaming phenomenon of the freeze-drying process of the drug!
Phenomenon: Many lyophilized drugs will blister, and the reasons for their analysis are mainly summarized as follows
Possible cause analysis and solutions:
1. Low temperature freezing is not strong;
2, did not grasp the nature of the material;
3. The vacuum is not well controlled;
4. There is a problem with the heating procedure;
5. The surface structure of the object to be lyophilized is dense, which is caused by the discharge of internal gas during drying;
6. The main phenomenon is that the pre-freezing is not caused by freezing. In the case of pre-freezing, the vacuum control is not good and will not foam, and heating too fast will cause dry loss;
7. If the vacuum control is not good, there will be a starting phenomenon, and the equipment should be well maintained;
8. Freeze, firstly freeze the product, the material thickness should be controlled as much as 15mm or less, and the excipients should be used. Slow freezing will help to form large ice crystals, which will help to improve the sublimation drying rate and reach 10 degrees below the eutectic point. After 1-2 hours
9. Sublimation drying, the condenser (water trap) is pre-cooled to -45 degrees and then vacuum is started. The vacuum is controlled at 50-100pa. (For the degree of vacuum, some books say 10-30pa, depending on the actual material. In case of suitable vacuum degree, if the vacuum is too low or the product is not frozen, the surface of the product will boil, and the bubbles will run out from the inside of the product, which will affect the appearance and sublimation rate of the product. At the same time, the product will start to heat slowly, and the temperature control should be controlled. The temperature of the product does not exceed its eutectic temperature, because simply speaking, the heating temperature does not melt the product (other methods are determined)
10. Foaming when a vacuum is applied, it is not frozen, and the material is not completely crystallized;
11. Heating for a period of time and then foaming, the heating is too fast, the material temperature exceeds the eutectic point temperature, so that the material melts and foams;
12. The first drying stage (sublimation stage) enters the analysis without ending, so that the ice-containing material that has not been sublimated is warmed up and melts and foams;
13. If the concentration is too high and has not been treated, a layer of crystalline salt is formed on the surface of the material during pre-freezing. This layer of crystalline salt seriously affects the passage of water vapor when the material is sublimated, so that the heating is very short (about 1 There will be a bulging phenomenon within a certain period of time, and it will cause serious blistering;