There are many ways to classify pharmaceutical freeze dryers. According to their shelf area, they can be divided into three types: large, medium and small. Usually, the freeze drying area is less than 1.5㎡ for small, between 1.5㎡ and 50㎡ for medium, and greater than 50㎡ for large; according to their purpose and use, they can be divided into experimental freeze dryers, pilot freeze dryers and industrial production freeze dryers.
Pharmaceutical freeze dryers are mainly composed of drying box, vacuum system, refrigeration system, cold trap system, heating system, capping system, automatic control system and other parts. In addition, large and medium-sized freeze dryers often have steam sterilization system (SIP) and cleaning in place system (CIP).
The refrigeration system provides cold source for freeze drying box and cold trap system respectively. The plate layer refrigeration temperature of the currently used single-stage refrigeration compression cycle is about -35℃～-40℃, and the cold trap temperature is about -50℃; the plate layer refrigeration temperature of the two-stage refrigeration compression cycle is between -45℃～-50℃, and the cold trap temperature is about -65℃; the plate layer refrigeration temperature of the cascade refrigeration cycle is between -55℃～-60℃, and the cold trap temperature is about -75℃.
The control of the freeze dryer is mainly to control the start and stop of the refrigerator, vacuum unit, heating power and temperature, and to measure and monitor the vacuum degree and temperature, as well as automatic protection and alarm devices. Freeze dryers using full automatic control or microcomputer control can display the working status of each major component, the temperature, vacuum degree, and water trap temperature of the shelves and drugs in the drying box, and can set, modify and display parameters in real time.
Pharmaceutical freeze dryers must comply with GMP standards to achieve high sterilization and dust-free, and achieve high reliability, safety, and easy maintenance. For this reason, pharmaceutical freeze dryers often use steam sterilization systems (SIP) to ensure thorough sterilization without dead corners. At the same time, they are supplemented by in-place cleaning systems (CIP) to clean the drying chamber, condenser, main valve and pipelines on site.
The preset drainage slope ensures that there is no liquid retention. At the same time, it has protection measures to deal with power outages, water outages and misoperation. Once a fault occurs, the drugs can be protected; the computer control of the operation of the freeze dryer is realized, and there is a three-countermeasure system for power outages and water outages, which can be multi-way interlocked and automatically alarmed.
Since pharmaceutical freeze dryers must comply with GMP standards, the research on pharmaceutical freeze dryers in the future will still be carried out in the direction of sterilization and high reliability, such as the research on automatic feeding methods and vacuum control methods.
With the rapid development of biotechnology, polypeptide and protein drugs continue to emerge, and polypeptides, proteases, hormones, vaccines, cell growth factors and monoclonal antibodies that can be used in clinical practice have become the focus of development.
In order to prevent drug denaturation, freeze drying is currently widely used to prepare solid drugs. After decades of development, although pharmaceutical freeze drying technology has made great progress, there are still many problems that need to be solved urgently. During the freeze-drying process, various freezing and drying stresses will be generated, causing the drugs to undergo denaturation to varying degrees.
In addition, the freeze-drying method itself also has disadvantages such as low drying rate, long drying time, high energy consumption during the drying process, and large investment in drying equipment.
Therefore, in order to improve the stability and economy of drugs, it is necessary to further study the damage and protection mechanism of drugs during the freeze-drying process, and at the same time, use advanced refrigeration and vacuum equipment and control methods to develop low-priced and high-performance freeze dryers, continue to improve the heat and mass transfer theory under low temperature and low pressure, and optimize the freeze-drying process.
