Troubleshooting in the Manufacturing of Freeze-Dried Drugs

There might occur some problems during the manufacturing of freeze-dried drugs. How to solve them? Hawachdryer listed out these problems and their corresponding causes and solutions. Come and see them now!

Problem 1 in the manufacturing of freeze-dried drug:

When the product is out of the chamber of the lyophilization machine, it is a large skeleton structure, even a fluffy substance, and the fluffy substance disappears after being out of the box.

Causes and solutions: the ingredient concentration is low, the product is loose and easy to attract moisture. At the same time, due to the large specific surface area, the product is easy to shrink. The dry product has too low mechanical strength. Once shaken, it will be dispersed into a powder and adhere to the bottle wall. Such a problem can be solved by increasing the amount of filler.Freeze-Dried Drugs

Problem 2 in the manufacturing of freeze-dried drug:

The product has no fixed shape after freeze-drying, and even the dried product is carried to the outside of the container by the sublimation airflow

Causes and solutions: this is because the concentration of solid matter in the product is too low to form a skeleton. If you have this question, the freeze dryer manufacturer may suggest you increase the solids concentration.

Problem 3 in the manufacturing of freeze-dried drug:

The structure or color of the product in the vertical direction is not uniform (layered)

Causes and solutions: 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. During the slow pre-freezing process, ice crystals are formed at the bottom and the solute is concentrated upwards, which can be solved by speeding up the pre-freezing process or using the repeated freezing method. 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 the storage time of the solution.

Problem 4 in the manufacturing of freeze-dried drug:

There is a hard shell on the surface of the product

Causes and solutions: during pre-freezing, an airtight glass-like structure is formed on the surface of the product, but the heat treatment is not performed. After the sublimation starts, the product heats up, and some products undergo melting and shrinkage. Product shrinkage makes its surface to split. Therefore, the sublimation of the lower layer can proceed normally. The solution is to do back heat treatment when frozen.lyophilization machine

Problem 5 in the manufacturing of freeze-dried drug:

There is a small protrusion in the middle of the surface of the product.

Causes and solutions: Some products will undergo a process from porridge to solidification when they are frozen. When solidified, the volume expansion will squeeze the porridge-shaped ice from the periphery to the middle, forming a sharp protrusion on the surface of the product. This is related to the prescription and rapid cooling during pre-freezing. Some freeze-dried protective agents are prone to form such small protrusions. For example, when lactose is used as a freeze-dried protective agent, this situation is likely to occur when the temperature is lowered too quickly during pre-freezing. Generally, it can be solved by changing the freeze-dried protective agent or changing the pre-freezing method.