Foam vacuum freeze drying technology for Pilot Freeze Dryer 

　　Foam vacuum freeze drying technology for Pilot Freeze Dryer 
　　The Pilot Freeze Dryer is constructed with versatility in mind so that this Pilot Freeze Dryer can meet any lyophilization requirement. Shelf temperatures as low as -70C and condenser temperatures to -85C supports a wide range of applications. Available in bulk or stoppering configurations and with up to 6 shelves. Each system is available with a selection of control formats and temperature and vacuum sensors.  allows you to configure a Pilot Freeze Dryer to meet your own particular application requirements.
　　 Pilot Freeze Dryer are widely used in the production of biopharmaceuticals, high-end foods and cosmetics, and ultrafine powders. Because the products have the advantages of long shelf life, convenient use, convenient transportation, and storage at room temperature, freeze-drying methods are often used in the preservation of vaccines and microorganisms. Compared with other common drying methods such as drying, the freeze-drying production has a long cycle and high energy consumption, which limits the application range of the freeze-drying technology.
　　In order to improve the efficiency of freeze-drying production, reduce its energy consumption and maintain the advantages of its products, in recent years, foreign scholars have proposed a new drying method for veterinary vaccines, foam vacuum freeze-drying, which is characterized by: The pre-treatment is carried out, the foaming agent is loaded, and the material is expanded into a foam shape by means of vacuuming, and then heated under vacuum to complete the first and second drying, thereby removing the moisture in the material. The new method has a significant increase in the specific surface area of ??the material after foaming, and the heat transfer and mass transfer conditions can be significantly improved, thereby greatly increasing the drying rate. Using this method, foreign scholars have dried and preserved influenza virus, mycoplasma, and burdock virus, and have achieved good experimental results. Some scholars have tried to use this method to dry food.
　　Public reports on foam vacuum freeze drying in China are still rare. In order to promote the application and promotion of foam vacuum freeze-drying technology in China, this paper intends to carry out experimental research on foam vacuum freeze-drying process, determine the main factors affecting foaming effect, and bottle 1ml sample with foaming effect. The foam was vacuum dried and dried.
　　Materials and Method
　　1.1, experimental materials
　　The foam vacuum freeze-dried formulation used in this experiment contains 40% sucrose, 2% arginine, 1% glycerol, 0.025 mol·L-1 phosphate buffer (pH 7.2), and a certain proportion of Pluronic-F68, gelatin. Preservation of a live vaccine against Newcastle disease in chickens. Among them, Pluronic F-68 acts as a foaming agent, which makes the solution bulky when the system is vacuumed; gelatin acts as a stabilizer to stabilize the foam structure.
　　1.2, experimental device
　　The lyophilizer used is produced in Shanghai. An electric heater is arranged below the shelf and its power output is controlled by the PLC to control the temperature of the shelf. The refrigeration system adopts a single-stage vapor compression type. The mixed refrigerant is compressed into high-temperature and high-pressure steam in the compressor and then enters the condenser. The condensed low-temperature and low-pressure fluid is divided into two paths, which are respectively in two manual throttle valves. The throttling and flow adjustment were carried out, and then the two fluids were respectively cooled into the shelf and the cold trap coil in the freeze-drying tank to complete a refrigeration cycle, and the temperature of the cold trap was about -60 ° C during the experiment. The vacuum pump is powered by three phases and is connected to the output end of the Siemens MICROMETTER 440 inverter. By controlling the pumping speed of the vacuum pump and adjusting the opening degree of the vacuum trimmer valve, the vacuum degree of the drying box can be accurately controlled. Sample internal temperature data was collected every 6 seconds using an Agilent data logger. After the sample is pre-cooled on the shelf, vacuum foaming begins. Because the vacuuming rate is too fast, the solution is sprayed, and in order to obtain a better foaming effect, the foaming process needs to be carried out in stages, first in the drying oven. A certain degree of vacuum is reached, and after two minutes, the vacuum is controlled to within 10 Pa.
　　1.3, experimental program
　　The foam vacuum freeze-drying process is as follows: pre-cooling→foaming→freezing→primary drying→secondary drying→sealing. The experiment consists of two parts. The * part determines the factors affecting the foaming effect by designing orthogonal experiments. The second part is carried out on the basis of * part, and the foam freeze-drying of 1 ml sample is carried out according to the process conditions corresponding to the Zuijia foaming effect. Through literature research and preliminary experiments, the authors determined the factors that affect the foaming effect of Pluronic F-68 and gelatin content, shelf temperature, and vacuum. The factor level range is shown in Table 1, and the orthogonal experiment table is arranged according to L9 (34). Each experiment was repeated three times. The index of the foaming effect is the foaming height and the primary drying time. The higher the foaming height and the shorter the drying time, the better the selected process conditions. The second part of the experiment steps are as follows: 1) Take 1 mL of the sample solution in a Φ22 mm vial, the height of the liquid is about 2.5 mm, cover the stopper with a half, place it on the shelf, pre-cool for 30 min; 2) pump Vacuum foaming; 3) drying once for 3 h; 4) drying the shelf temperature to 32 °C for secondary drying for 12 h; 5) measuring the remaining water content of the sample using dry weighing method, electronic balance using METTLER - Toledo's AL104 with an accuracy of 0.1 mg and repeated three times in the experiment.
　　According to the author's preliminary experimental results, the vacuum is directly pumped to such a low level that the foam is easily broken and even causes the spray bottle. Therefore, a vacuum pumping method is adopted in the foam freeze-drying experiment, and the vacuum level of the foaming stage is based on The initial experiment range is 50~200 Pa. From the experimental results of this paper, as long as the foaming achieves a certain effect, as shown in Table 2, the Zui is 13 mm small, and the ratio of the initial liquid to the height is 5.2, which has a limited effect on the drying time. For the influence of the secondary drying time, the author did not conduct research due to the limitations of experimental conditions, but from the theory of heat and mass transfer, it can be expected that the secondary drying time will be shortened as the foaming effect becomes better. According to the results of the second part of the experiment, foam vacuum freeze-drying technology for 1 ml samples reached a residual water content of less than 2%, which took less than 16 hours, which is about half of the traditional freeze-drying time.
　　Summary
　　As an emerging drying technology, foam vacuum freeze-drying not only maintains some of the advantages of freeze-drying to the product, but also shortens production time, reduces production energy consumption, and has certain advantages in terms of production efficiency and cost. In this paper, a foam vacuum freeze-drying experiment was carried out on a solution containing the common lyoprotectant sucrose. The four factors that may affect the foam formation and stability were orthogonally studied and combined with the factors of foaming effect. The remaining water content of the sample is tested. The residual moisture content of the sample can also reach a level of less than 2% in the case where the drying time is significantly shortened. The results obtained in this paper have guiding value for the development of foam vacuum freeze-drying process.