Analysis of the causes of blistering of lyophilized products in freeze dryers and their solutions

Phenomenon: Many lyophilized drugs will appear foaming. The reason for the analysis is mainly summarized as follows

Possible cause analysis and solution

1. Freezing is not strong

2. Did not master the nature of the material

3. The vacuum is not well controlled

4. There is a problem with the heating program

5. The surface structure of the freeze-dried object is dense, and the internal gas is discharged when dry.

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 damage.

If the vacuum control is not good, there will be blistering, and the equipment should be well maintained.

6. Freezing First, the product should be frozen, and the thickness of the material should be controlled as much as 15mm or less. Using the excipients, slow freezing will help to form large ice crystals, which will help to improve the sublimation drying rate. After reaching 10°C below the eutectic point, Keep 1-2 hours

7. Foaming when vacuuming, it is not frozen, the material is not completely crystallized. After heating for a period of time and then foaming, it belongs to heating too fast, the material temperature exceeds the temperature of the eutectic point, so that the material melts and foams.

8. The first drying stage (sublimation stage) enters the analysis without ending, so that the temperature of the ice-containing material that has not been sublimated rises and melts and bubbles.

9. 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 during sublimation of the material, so that the sample is just warmed up very short (about one hour). During the time of the left and right, there will be a bulging phenomenon, which will cause serious blistering.