Exploring the effective control of key links in the process of drug freeze-drying

The lyophilization process of the drug includes five steps of sample preparation, pre-freezing, primary drying (sublimation drying) and secondary drying (analytical drying), sealing and storage, and the temperature, freezing speed and vacuum degree are strictly controlled in each stage. The author understands that there are many factors affecting the lyophilization process of drugs, and various factors still have a related role. Therefore, in order to obtain a good freeze-dried drug, it is necessary to effectively control all aspects of the freeze-drying process.

For example, in terms of product prescriptions, relevant experts said that to ensure the freeze-drying effect, prescription is the first problem to be solved, because prescription is the basis for research on freeze-drying process. When the drug prescriptions are different, the melting point and residual moisture requirements will be different. For products with a low eutectic point, the temperature required for pre-freezing is also low, and the temperature of the slab is lower when heated. For products with low moisture content, the freeze-drying time should be longer, and the product with high moisture content will shorten the freeze-drying time.

In addition, before lyophilization, the operator should do a sufficient research on raw materials, auxiliary materials, etc., such as try to choose a lyophilized protective agent with a higher eutectic point to facilitate the smooth progress of the sublimation stage and shorten the freeze-drying time. Choose a suitable antioxidant, acid-base regulator to ensure the stability of the product.

According to relevant sources, when the solid content in the prescription is less than 2%, the lyophilized product may be broken or even detached from the container during the drying process. If less than 30%, the concentration of the lyophilized product will become high, hindering the flow of water vapor during the drying process, resulting in prolonged lyophilization time or high moisture content of the final product.

Product pre-freezing is also an important part. Usually, when the product is freeze-dried, it is placed in a suitable container for pre-freezing before sublimation drying. It should be reminded that pre-freezing is actually an important part of the freeze-drying process, because the pre-freezing process is not only to protect the main properties of the material, but also to provide a reasonable structure for the sublimation of the product after lyophilization. . Therefore, three factors need to be determined before pre-freezing, namely the minimum temperature for pre-freezing, the speed of pre-freezing and the time for pre-freezing.

In terms of pre-freezing speed, the speed of pre-freezing can directly affect the subsequent sublimation drying process, mainly in the form of slow freezing and quick freezing. In terms of slow freezing, one is to reach the freezing temperature for a long time; the other is to maintain the temperature near the eutectic point (porridge ice) for a while, then lower the temperature. There are three ways of quick freezing. One is that the machine is cooled at full speed after the product enters the freeze dryer; the second is that after the product enters the freeze dryer, the temperature of the plate is maintained at about 0 °C (the product is not frozen), so that the product is at The liquid is at a lower temperature, and then the machine is cooled at full speed; the third is to first cool the sheet to -30 ° C to -35 ° C, then put the product into the product and the machine is cooled at full speed.

In terms of pre-freezing time, experts said that it is decided according to the condition of the machine, to ensure that all products are frozen before vacuuming. When the bottle is ejected from the vacuum, the temperature difference between each shelf of the shelf is smaller, and the pre-freezing time can be shortened accordingly. The temperature of the general product reaches the pre-freeze. Vacuuming and sublimation can be started 1 to 2 hours after the lowest temperature.

If you can pay attention to the above factors, the lyophilization process of the drug will be smoother. Good freeze-dried drugs generally have good physical forms, such as full shape, smooth surface, no shrinkage, uniform color, good porosity, qualified moisture content, rapid reconstitution after adding water, and long-term storage.

However, in the production process of freeze-dried products, there are often some abnormal conditions, such as spray bottle, falling bottom, broken bottle, incomplete product drying, high water content, uneven content or low content, reconstituted content Liquid turbidity and other issues. If there is a problem, the operator should not be too alarmed, find the right method, or contact the professional, the relevant manufacturer can solve it.

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