Why do freeze-dried products control water content
In the production process of freeze-dried powder injection, some abnormalities often occur, affecting the product quality. The production personnel must effectively control the prescription design of the product, production process parameters, production environment control, the sanitation of the operating staff and other aspects, and effectively verify the production equipment, clean area environment, freeze-drying curve, so as to effectively avoid the abnormal phenomenon of freeze-drying products and improve the product quality.
■ Phenomenon 1: water content exceeds the standard
The water content specified in the freeze-dried powder injection quality standard is low. The main reasons for the water content exceeding the standard are: too much liquid medicine in the container and too thick liquid medicine layer; Insufficient heat supply during drying reduces evaporation; The vacuum degree is not enough, and the water vapor cannot be discharged smoothly; The temperature of the condensation chamber is too high to capture the water vapor effectively; The freeze-drying time is short; The air humidity of the vacuum drying box is high; The temperature of the product is lower than the room temperature and the product is hygroscopic when it is out of the box.
Measures: Production personnel must take corresponding solutions for different reasons. If the specification of the penicillin bottle is adjusted according to the volume of the drug solution to reduce the filling thickness, it should be controlled within 10~15mm generally; Strengthen heat supply and promote water evaporation; Check the cause of low vacuum and eliminate the abnormality of the dew point or vacuum system; Reduce the condenser temperature below - 60 ℃; Re-produce the freeze-dried curve to ensure that the water content of the freeze-dried products is qualified; The gas put into the box shall be sterilized, dehydrated and dried, especially the products easy to absorb moisture; The temperature at the time of product delivery is slightly higher than the production environment temperature.
■ Phenomenon 2: bottle spray
The reason for bottle spray is that the temperature does not reach the melting point of the product during pre-freezing, and the product is not frozen; Or when sublimation drying, the temperature rises too fast, local overheating, part of the products melt into liquid, and under high vacuum conditions, a small amount of liquid is sprayed from the dried solid surface through the pores to form.
Measures: In order to prevent bottle spray, the pre-freezing temperature should be strictly controlled at 10 ℃~20 ℃ below the melting point, and maintained for more than 2 hours, so that the temperature of the drug can be increased after freezing. At the same time, the heat supply during sublimation drying should be well controlled, the heating rate should be appropriately slowed down, and the temperature should not exceed the melting point. This can overcome the bottle spray phenomenon.
■ Phenomenon 3: unqualified appearance
The normal appearance of the lyophilized powder needle should be uniform in color, dense in pores, basically unchanged in volume and shape before lyophilization, and form a massive or spongy mass structure. However, if the weight concentration of the solution is greater than 30%, the product is prone to shrinkage, collapse and fullness. In addition, during drying, the frozen surface is first dehydrated to form a dense dry shell, and the sublimated water vapor below escapes from the gap between molecules on the dried surface. At this time, if the solution concentration is too high, the gap between molecules is small, the ventilation is poor, the resistance of water vapor passing through is large, a large number of water molecules can not escape in time, and the stagnation time in the drying layer is long, so that some dried drugs gradually deliquescence, which will make the volume of the product shrink, and the appearance is not full or collapse. If the weight concentration of the liquid medicine is lower than 4%, the medicine will fly away with the water vapor when vacuuming; Or it becomes fluffy loose structure after drying. After the vacuum is removed, the material of this structure will dissipate, making the product become hollow. Another situation is that the concentration of the liquid medicine is too low, which makes the product loose and easy to get wet. At the same time, due to the large specific surface area, the product is easy to shrink, and the mechanical strength of the dry finished product is too low. Once it is vibrated, it will disperse into powder and adhere to the bottle wall.
