Pharmaceutical freeze dryerDuring use, due to the different characteristics of different products, it is inevitable to encounter different freeze-drying problems during operation. Next, we will discuss with you the phenomenon of foaming during the freeze-drying process of drugs!
Phenomenon: Many freeze-dried drugs will produce bubbles. Based on the analysis of the reasons, they can be summarized as follows
Possible reasons analysis and solutions:
1. Low temperature freezing is not firm;
2. Not mastering the properties of materials well;
3. The vacuum is not well controlled;
4. There is a problem with the heating program;
5. The surface structure of freeze-dried objects is dense, which is caused by the discharge of internal gases during drying;
6. The main phenomenon is that the pre freezing is not well frozen, and if the vacuum control is not good after pre freezing, it will not bubble, while heating too quickly can cause drying damage;
7. If the vacuum control is not good, there will also be starting phenomenon, and the equipment needs to be well maintained;
8. To freeze, first freeze the product thoroughly, with the material thickness controlled below 15mm as much as possible. Use excipients, and slow freezing can help form large ice crystals, thereby improving the sublimation drying rate. After reaching 10 degrees below the eutectic point, maintain it for 1-2 hours
9. Sublimation drying, the condenser (water trap) is pre cooled to -45 degrees and then vacuumed, with the vacuum controlled at 50-100pa (some books say it is 10-30pa, depending on the actual situation, choose the appropriate vacuum degree according to different materials. If the vacuum is too low or the product is not completely frozen, the surface of the product will boil, and bubbles will run out from the inside of the product, affecting the appearance and sublimation rate of the product). At the same time, the product is slowly heated, and the temperature control should not exceed its eutectic temperature, because in simple terms, the heating temperature cannot melt the product (there are other methods to determine)
10. Bubbling occurs immediately upon vacuuming, indicating that the material has not frozen and has not fully crystallized;
11. Heating for a period of time before foaming is considered too fast, causing the material temperature to exceed the eutectic point temperature, resulting in melting and foaming of the material;
12. The first drying stage (sublimation stage) enters the analysis stage before it is completed, causing the ice containing material that has not been sublimated to rise in temperature and melt into bubbles;
13. If the concentration is too high without treatment, a layer of crystalline salt will form on the surface of the material during pre freezing This layer of crystalline salt seriously affects the passage of water vapor during material sublimation, causing bulging and severe foaming within a short period of time (about 1 hour) after heating;