Vial is the main packaging form of sterile powder injection drugs now, and the use is large. At the same time, vacuum freeze drying technology has developed very rapidly in recent years, after nearly ten years of market competition and optimization combination, many vacuum freeze dryer professional manufacturers have been formed. The technical performance of pharmaceutical vacuum freeze dryer has been basically mature, and the corresponding industry standards have also been formulated in China. From the perspective of the actual production problems, since the use of domestic vials, it was found that the problem of broken bottles in the freeze-drying process was relatively prominent, so the relevant departments did a lot of work, starting from the process, equipment, and the quality of vials, and finally solved this long-troubled problem.
1. The reason of equipments manufacturing
At present, there are still many shortcomings in domestic freeze dryers, and manufacturing enterprises do not have unified standards due to different comprehensive technical quality, different design structure and manufacturing process. Some manufacturers' product shelves are not flat, especially for larger area shelves, when the stopper is carried out after lyophilization, the pressure distribution is uneven, resulting in individual bottles being crushed.
2. The quality of vial bottle itself
This is an important factor affecting the rate of freeze-dried bottle breakage. We know that before filling, vials need to undergo ultrasonic cleaning and high temperature sterilization to remove heat sources, no matter which process, it is a test for vials. The intensity of ultrasonic waves and the impact of water vapor in cleaning will have a certain impact on the glass, and the uneven distribution of the temperature of the tunnel oven is easy to produce sudden heat and cooling, which is more harmful to poor quality vials. Perhaps the appearance of the bottle is not visible to the naked eye, but it may create tiny cracks that are not enough to withstand the temperature changes in the later lyophilization process. The vials of each brand have different degrees of broken bottles, and the serious ones even reach more than 10%.
3. The influence of freeze dried-process
While investigating the quality of vials, we focused on the freeze-drying process and analyzed the reasons for broken bottles. Generally, glass bottles have a large temperature tolerance range without chipping when evenly heated, such as baking in the oven or freezing in an environment of minus tens of degrees Celsius. However, if the temperature of different parts of the same bottle (especially the bottom of the bottle) changes sharply or hotly, forming a relatively large temperature difference, each part of the bottle will be subjected to different expansion forces, and when this force exceeds the bearing capacity of the glass, it will inevitably lead to damage to the glass.This situation is easy to occur during the freeze-drying process. The key to solving the problem of chipping and bottoming is to reduce the temperature difference between the parts of the glass bottle, which is reflected in the lyophilization process curve is to reduce the temperature line interval between the shelf temperature curve and the sample temperature curve. This can be achieved in practice by vacuum control and temperature control.
4. Methods of detection
In terms of incoming inspection, many pharmaceutical companies have not yet tested vials, often referring to the technical parameters provided by packaging plants, without combining the actual situation of vacuum freeze dryers. In this regard, it is recommended to consider the necessary inspection of the quality of vials, and in view of the impact of hot and cold changes on vials, it is necessary to use a glass bottle thermal shock tester for thermal shock test.In view of the bottom missing of the vial, the main reason is that there is stress concentration in the bottom part of the bottle body, and the polarizing stress meter should be used for residual stress test. In addition, the uniformity of the wall thickness of the vial will also affect the stability of the product, and the wall thickness gauge can be used to test the thickness of the wall at the bottom of the bottle.