What Are The Common Problems In The Lyophilization Of Drugs And How To Solve Them?

Common problems in the lyophilization of drugs:

In the lyophilization of drugs, some abnormal situations often occur, such as sample shrinkage, no fixed shape, incomplete pre-freezing, etc. These all can be called lyophilization failures. Then here comes the question, how to solve these problems, or to say, how to avoid these failures? 

Drug lyophilization troubleshooting

Drug lyophilization troubleshooting – situation 1

Shortly after the product is out of the chamber of the lyophilization machine, there are shrinkage, cavities, incomplete drying of broken pieces, residual ice crystals, etc. Such problems can be solved by extending the sublimation drying time or increasing the sublimation temperature.lyophilization of drugs

Drug lyophilization troubleshooting – situation 2

After the product is freeze-dried using the freeze dryer lyophilizer, there is no fixed shape, and even the dried product is carried to the outside of the container by the sublimation airflow. This is because the solid matter concentration in the product is too low to form a skeleton. The solution is to increase the solids concentration.

Drug lyophilization troubleshooting – situation 3

The pre-freezing temperature is too high, or the time is too short, and the pre-freezing is incomplete. It can be solved by lowering the pre-freezing temperature and extending the pre-freezing time.

Drug lyophilization troubleshooting – situation 4

The structure or color of the product in the vertical direction is uneven (layered). One situation is that the lower part of the freeze-dried block is fine and the upper part is frizzy and has crystalline patterns. This is caused by the slow freezing rate, which can be solved by speeding up the pre-freezing speed or using repeated freezing methods. Another situation is that the concentration of a certain substance in the solution is too high. After the solution is left for a long time, the substance will precipitate out due to the change of temperature or pH value. You can reduce the concentration and adjust the prescription to stabilize the pH value of the solution or reduce its storage time.

Drug lyophilization troubleshooting – situation 5

The surface of the product has a hard shell. The surface of the product forms an air-tight glass-like structure during pre-freezing, but it is not subjected to heat treatment. After the sublimation starts, the product heats up, and some products melt and shrink. The shrinkage of the product causes the surface to split. The solution is to do back heat treatment during pre-freezing.

Drug lyophilization troubleshooting – situation 6

The surface of the product is cracked. In most cases, this is caused by the low solid matter concentration and the fragile structure of the product block. The second stage drying speed can be slowed down to limit the material loss, but the overall excipient concentration should be increased to strengthen the structure of the product block.

Hawachdryer listed 6 situations of lyophilization failures and the corresponding troubleshooting methods. Can you come up with other yophilization failures and the solutions to them? Contact us if you have any other ideas.