WO2017084163A1

WO2017084163A1 - Vacuum spray-freeze-drying apparatus and method

Info

Publication number: WO2017084163A1
Application number: PCT/CN2015/098808
Authority: WO
Inventors: 郑效东
Original assignee: 上海东富龙科技股份有限公司
Priority date: 2015-11-17
Filing date: 2015-12-24
Publication date: 2017-05-26
Also published as: CN105318666A

Abstract

A vacuum spray-freeze-drying apparatus and method. The vacuum spray-freeze-drying apparatus comprises: a sealed container (1) used for containing a material during the vacuum spray-freeze-drying process; an atomizing nozzle (2) used for atomizing and dispersing liquid to be freeze-dried into liquid drops and spraying the liquid drops into the container (1); a vacuum system used for creating a vacuum environment in the container (1) during the vacuum spray-freeze granulation stage to make some of the components of the liquid drops be vaporized and absorb heat to cool and freeze the liquid drops into granules, and continuing vacuum pumping during the drying process to maintain the vacuum environment; and a temperature adjusting sleeve (6) used for cooling during the vacuum spray-freeze granulation stage to avoid melting of some of the components in the granules, and providing heat for sublimation of some of the components in the granules during the drying process. No refrigerant is in contact with the material during a quick-freezing process of the material, thereby avoiding the risk of contamination of the material and ensuring the sterility of the freeze-drying process.

Description

Vacuum spray freeze drying equipment and method

Technical field

The invention relates to a vacuum spray freeze-drying device and a method, which are used in a pharmaceutical freeze-drying workshop and belong to the field of vacuum freeze-drying technology.

Background technique

As shown in FIG. 1, the conventional freeze-drying process holds the liquid to be lyophilized in a container under a normal pressure and places it on the horizontally disposed plate layer 100. The plate layer 100 first cools the liquid to be freeze-dried into ice cubes. Liquid from room temperature (25 ° C) to -40 ° C usually exceeds 30 minutes, is a slow freezing technology, for non-solution distribution of material liquid (such as suspension, emulsion), prone to material sedimentation, liquid stratification And slow freezing is prone to ice crystal growth, which is not conducive to freeze drying. After the liquid is pre-frozen, the conventional lyophilizer draws the container into a vacuum and then removes the water in the ice cube by sublimation through the layer heating. Because the material is always standing during the drying process, only the small area of the bottom is in contact with the plate layer, the heat transfer effect is poor and the drying time is long; the upper surface of the static material is first dried, and the dry layer gradually descends toward the frozen layer. In the stage, the dry layer becomes a hindrance to the outward diffusion of the sublimation gas in the frozen layer, and the mass transfer effect is poor, which further prolongs the drying time; in addition, the drying of the static material also places high demands on the uniformity of the lamellar temperature.

US Patent Publication No. US20130118026A1 discloses a spray freeze-drying technique in which a liquid to be lyophilized is sprayed from a nozzle above a container, and another set of nozzles sprays a refrigerant (liquid nitrogen, boiling point -196 ° C) to be frozen. The dry droplets are in contact with the refrigerant during the falling process, and ice particles are formed after the quick freezing. The container in the refrigeration stage is normal pressure or positive pressure. In the drying stage, the material at the bottom of the vessel is stirred by a stirrer, and the material is dried by heating with a jacketed cone wall at the bottom of the vessel.

Another quick-freezing technique is to place liquid nitrogen at the bottom of the container, and the lyophilized liquid is sprayed or dripped from above, and is frozen through the low temperature zone of liquid nitrogen. Freeze-drying processes are widely used in, but not limited to, the pharmaceutical industry, and their products have stringent requirements for clean, sterile pharmaceutical processes. The above two quick freezing technologies use the refrigerant (liquid nitrogen) to directly contact the material for refrigeration. The cleanliness and sterility are difficult to ensure, and the refrigerant is vaporized after heat exchange. Re-formation of the liquid requires great energy, and direct discharge is easy to cause. Waste and pollution.

In summary, how to improve the freezing and drying rate of the freeze-dried liquid in freeze-drying, more importantly how to ensure the cleanliness and sterility of the product during the process, to avoid the risk of contamination of the drug, and to reduce The reduction of energy consumption to the environment has become an urgent problem to be solved by those skilled in the art.

Summary of the invention

The object of the present invention is to provide a vacuum spray freeze-drying apparatus and method, which solves the problem that the freeze-drying liquid to be freeze-dried in the conventional freeze-drying has low slow-freezing efficiency, affects the quality of the freeze-dried product, has low static drying efficiency, and avoids the quick freezing process. The use of refrigerant to contact materials is likely to cause pollution, and the energy consumption is high and wastes and pollutes the environment.

In order to solve the above technical problem, the technical solution of the present invention is to provide a vacuum spray freeze-drying apparatus, comprising: a closed container for accommodating materials in a vacuum spray freeze-drying process; and a liquid to be lyophilized An atomizing nozzle that is atomized and dispersed into droplets and sprayed into the container; for forming a vacuum environment in the container during the vacuum spray freeze granulation stage to vaporize some of the components in the droplets to thereby cause heat absorption Cooling the droplets to form particles and maintaining the vacuum system of the vacuum environment during the drying phase; and for cooling in the vacuum spray freeze granulation stage to avoid melting of some of the components of the particles and providing them during the drying phase A temperature-regulating jacket for sublimation heat of a portion of the particles.

Preferably, part of the droplets are water and part of the particles are ice.

Preferably, said vacuum spray freeze drying apparatus further comprises said particles for condensing a portion of said droplets after vaporization in a vacuum spray freeze granulation stage and/or said sublimation after drying in a drying stage a condensing device for condensing a portion of the components; said vessel being provided with means for rotating in a vacuum spray freeze granulation stage to avoid agglomeration of said frozen particles into ice cubes, and rotating said particles during the drying phase An agitating paddle that heats up and down the inner wall of the container and allows the sublimation gas to escape from the gap between the particles, the agitating paddle being located at a lower portion of the container.

More preferably, the agitating paddle is connected to the motor via a connecting shaft.

More preferably, the condensing device is one or a combination of a cooling jacket and a condenser, the cooling jacket is disposed outside the upper portion of the container, and the inside of the cooling jacket is provided with a refrigerant. The condenser is disposed outside the container and is coupled to the container.

Further, the vacuum system includes a vacuum pump, and the container is provided with a connection port; when the condensing device is a cooling jacket, the vacuum pump connects the connection port of the container through a pipe, a valve is provided on the pipe; when the condensing device is a condenser or a combination of a cooling jacket and a condenser, The condenser is connected to the connection port of the container through a pipe, the vacuum pump is connected to the condenser through another pipe, and a pipe is arranged on the pipe between the condenser and the connection port of the container.

Further, a filter is arranged on the connection port of the container.

Further, the refrigeration jacket has a refrigerant inlet and a refrigerant outlet, wherein the refrigerant inlet and the refrigerant outlet are respectively connected to two ends of the refrigerant circulation pipeline, and the refrigerant circulation pipeline is provided with a fluid pump and a refrigerant for the refrigerant. a temperature-reducing heat exchanger; the temperature-regulating jacket is provided with a temperature-regulating fluid, the temperature-regulating jacket has a temperature-regulating fluid inlet and a temperature-control fluid outlet, and the temperature-control fluid inlet and the temperature-regulating fluid The outlets are respectively connected to two ends of the temperature regulating fluid circulation line, and the temperature regulating fluid circulation line is provided with a fluid pump and a heat exchanger and a heater for adjusting the temperature of the temperature regulating fluid.

Further, the heat exchanger is connected to a refrigeration system.

Further, the refrigeration system is a compressor.

Further, the refrigerating jacket has a rectangular cross section and is disposed in a circle around the upper portion of the container; or the refrigerating jacket has a semicircular cross section and spirally surrounds the The upper portion of the container is provided in the form of a plurality of turns, and the refrigerant in the cooling jacket may be silicone oil.

Further, the temperature control jacket has a rectangular cross section and is disposed in a circle around the lower portion of the container; or the temperature control jacket has a semicircular cross section and spirally surrounds the The lower portion of the container is provided in the form of a plurality of turns, and the temperature regulating fluid in the temperature control jacket may be silicone oil.

Preferably, the droplets are not in direct contact with the refrigerant within the container.

Preferably, the container is a closed container, the upper part is cylindrical and the lower part is tapered.

Preferably, the atomizing nozzle is connected to a closed liquid distribution pipe, and the liquid distribution pipe is provided with a pipe flow regulating valve.

Preferably, the bottom of the container is provided with a discharge valve for discharging dry material, and the discharge valve is connectable to the receiving device.

Preferably, at least one vibrator for shaking off the material is provided on the outer side of the top wall and the upper side wall of the container.

More preferably, the vibrator is driven by a gas piston to drive vibration or motor drive vibration.

Preferably, the vacuum spray freeze-drying apparatus further comprises a cleaning and sterilizing system for introducing clean water into the closed container for cleaning, and introducing a disinfectant into the closed container for sterilization, the disinfectant may It is sterile pure steam.

Preferably, the vacuum spray freeze-drying apparatus further comprises a control system for programmatically controlling the vacuum spray freeze-drying process, the control system comprising a programmable logic controller (PLC) and a computer (PC) at least one.

The invention also provides a vacuum spray freeze-drying method, characterized in that the vacuum spray freeze-drying device described above is used, comprising:

Step 1: Vacuum spray freeze granulation stage: firstly, the closed container is evacuated to a certain degree of vacuum by a vacuum system, and then the liquid to be lyophilized is atomized and dispersed into droplets and sprayed into the container by using an atomizing nozzle. Some of the components of the droplets vaporize and absorb heat in a vacuum environment to lower the temperature of the droplets, and the condensing device condenses a portion of the vaporized droplets to maintain the contents of the container The degree of vacuum, the temperature of the droplet continues to drop until freezing forms particles, and the temperature-regulating jacket is cooled at this stage to prevent the ice in the frozen formed particles from melting, and the stirring paddle is rotated to avoid the freezing. The formed particles agglomerate into ice cubes;

Step 2: Drying stage: spray freeze granulation is finished, the vacuum system is continuously evacuated to maintain the degree of vacuum in the vessel, and then the temperature-regulating jacket is heated to provide sublimation heat of some components in the pellet The continuous rotation of the stirring paddle causes the frozen formed particles to roll up and down to fully and uniformly exchange heat with the container wall, and the sublimation gas escapes from the gap between the particles, and then is condensed by the condensation device until the material is completed. dry;

Step 3: After the material is dried, a dry clean sterile gas is introduced into the closed container to balance the pressure, and the dried material is collected.

Compared with the prior art, the beneficial effects of the present invention are:

1. The invention is completely different from the slow freezing technology of the liquid standing under the traditional freeze-drying normal pressure, and the liquid is pre-frozen into ice particles by the vacuum freeze granulation technique, thereby greatly improving the freezing rate; the vacuum freezing provided by the invention The granular technology does not have a refrigerant nozzle. The equipment does not have a liquid nitrogen low temperature zone. The refrigerant does not use the refrigerant to contact the material during the quick freezing process, completely eliminating the risk of contamination of the material, improving the sterility of the freeze-drying process and reducing the energy consumption of the production. .

2. The vacuum spray freeze granulation technology disperses the material into solid ice particles in advance, so that the dynamic heating of the dry material can be realized, the heat and mass transfer effect in the traditional freeze-drying process is improved, and the efficiency of freeze-drying is greatly improved. Short freeze-drying cycle further reduces production energy consumption.

DRAWINGS

Figure 1 is a schematic view showing the structure of a conventional lyophilizer.

2 is a schematic view showing the structure of a vacuum spray freeze-drying apparatus in Embodiment 1.

3 is a schematic structural view of a vacuum spray freeze-drying apparatus in Embodiment 2.

4 is a schematic structural view of a vacuum spray freeze-drying apparatus in Embodiment 3.

detailed description

The invention is further illustrated below in conjunction with specific embodiments. It is to be understood that the examples are not intended to limit the scope of the invention. In addition, it should be understood that various changes and modifications may be made by those skilled in the art in the form of the present invention.

Example 1

2 is a schematic structural view of a vacuum spray freeze-drying apparatus in Embodiment 1, the vacuum spray freeze-drying apparatus comprising: a closed container 1 for accommodating materials in a vacuum spray freeze-drying process; The lyophilized liquid is atomized and dispersed into droplets and sprayed into the atomizing nozzle 2 in the container 1; for forming a vacuum environment in the container 1 in the vacuum spray freezing granulation stage to make the water in the droplets Vaporizing the endotherm to further cool the droplets to form particles, and continuously evacuating during the drying phase to maintain the vacuum system of the vacuum environment; and for cooling in the vacuum spray freeze granulation stage to avoid ice in the particles a temperature regulating jacket 6 that melts and provides sublimation heat of ice in the granules in a drying stage, and condenses the vaporized vaporized water in a vacuum spray freezing granulation stage and the granules after sublimation in a drying stage a condensing device for condensing water vapor, wherein the container 1 is provided for rotating in a vacuum spray freezing granulation stage to prevent the freezing formed particles from agglomerating into ice, and drying Stage rotation causes the particles to roll up and down to exchange heat with the inner wall of the container 1 and to evaporate the water vapor from the gap between the particles. The stirring paddle 16 is located at the lower portion of the container 1. The agitating paddle 16 is connected to the motor 7 via a connecting shaft.

The container 1 is a closed container, the upper part is cylindrical and the lower part is tapered. The condensing device is a cooling jacket 3, and the cooling jacket 3 is disposed outside the upper portion of the container 1, and the inside of the cooling jacket 3 is provided with a refrigerant. The temperature control jacket 6 is disposed outside the lower portion of the container 1. The droplets are not in direct contact with the refrigerant in the container 1.

The refrigeration jacket 3 has a refrigerant inlet and a refrigerant outlet, and the refrigerant inlet and the refrigerant outlet are respectively connected to two ends of the refrigerant circulation pipeline, and the refrigerant circulation pipeline is provided with a fluid pump 4 and is used for the refrigerant. Cooling heat exchanger 5. The cooling jacket 3 has a rectangular cross section, and is disposed in a circle around the upper portion of the container 1. The refrigerant in the cooling jacket is silicone oil. The temperature regulating jacket 6 has a temperature regulating fluid, and the temperature regulating jacket 6 has a temperature regulating fluid inlet and a temperature regulating fluid outlet, and the temperature regulating fluid inlet and the temperature regulating fluid outlet are respectively connected to the temperature regulating temperature. At both ends of the fluid circulation line, the temperature control fluid circulation line is provided with a fluid pump 4 and a heat exchanger 5 and a heater 17 for adjusting the temperature of the temperature control fluid. The temperature regulating jacket 6 has a rectangular cross section and is arranged around the lower part of the container 1; the temperature regulating fluid in the temperature regulating jacket 6 is silicone oil. The heat exchanger 5 is connected to a refrigeration system. The refrigeration system is a compressor. The cooling jacket 3 and the temperature regulating jacket 6 are arranged at intervals.

The atomizing nozzle 2 is connected to a closed liquid distribution pipe 8 to be lyophilized, and the liquid distribution pipe 8 is provided with a pipe flow regulating valve 9. The vacuum system includes a vacuum pump 10, and the container 1 is provided with a connection port for connecting with the vacuum pump 10. The vacuum pump 10 is connected to the connection port of the container 1 through a pipe 11, and the pipe 11 is provided. There are valves 12. A filter 13 is disposed on the connection port of the container 1. The bottom of the container 1 is provided with a discharge valve 14 for discharging dry particles. The discharge valve 14 can be connected to a receiving device. The top wall of the container 1 and the outer side of the upper side wall are each provided with a vibrator 15 for shaking off the material. The vibrator 15 is driven to vibrate by a motor. The vacuum spray freeze-drying apparatus further includes a cleaning and sterilizing system for introducing clean water into the container for cleaning, and introducing a disinfectant into the container for sterilization, the disinfectant may be sterile pure steam. .

The liquid to be lyophilized may be an aqueous solution, a suspension, an emulsion, or the like of the drug, and may or may not include an auxiliary material, for example, an aqueous solution of ivy powder obtained by dissolving 125 g of ivy powder in 2 L of water, as described. When the device is used, the following steps are included:

Step 1: In the vacuum spray freezing granulation stage, the temperature of the silicone oil in the cooling jacket 3 is controlled to be -60 ° C, and the temperature of the silicone oil in the temperature regulating jacket 6 is -20 ° C, and the sealed container is firstly opened by a vacuum system. 1 pumping a certain degree of vacuum, the degree of vacuum is 300Pa, the aqueous solution of the ivy powder is delivered to the atomizing nozzle 2 through the liquid distribution pipe 8, the spray pressure is 0.4 MPa, the nozzle diameter is 1.0 mm, and the atomizing nozzle 2 is used. The aqueous solution of the ivy powder is atomized and dispersed into droplets and sprayed into the container 1. The water in the droplets vaporizes and absorbs heat in a vacuum environment to lower the temperature of the droplets, and the vacuum system continues to evacuate, and the refrigeration jacket 3 is vaporized. The water vapor condenses on the inner wall of the container 1 to maintain the degree of vacuum in the container 1, and the temperature of the droplet continues to decrease until Freezing to form granules, the process is completed in only a few seconds, the formed particles fall to the lower part of the container 1, and the tempering jacket 6 cools the lower portion of the container 1 to prevent the ice in the frozen formed particles from melting. The stirring paddle 16 rotates to prevent the particles formed by the freezing from agglomerating into ice cubes;

Step 2: In the drying stage, the spray freeze granulation is finished, the vacuum system is continuously evacuated to maintain the degree of vacuum in the vessel 1, at this time, the degree of vacuum is 100 Pa, and then the temperature regulating jacket 6 is gradually heated to provide The sublimation heat of the ice in the granules is heated at a temperature of 35 ° C, and the stirring paddle 16 is continuously rotated so that the frozen particles are tumbling up and down to sufficiently and uniformly exchange heat with the inner wall of the vessel 1 and to sublimate water. The vapor escapes from the gap between the particles and is subsequently condensed by the cooling jacket 3 for a drying time of 4 h until the drying of the material is completed, so that the frozen formed particles are completely dried in the container 1.

Step 3: After the material is dried, a dry clean sterile gas (such as air or nitrogen) is introduced into the container 1 to make a pressure balance with the pressure difference between the inside and the outside of the receiving device, and then dried by the discharge valve 14. The material is discharged and the dry material is collected by a receiving device.

The vacuum spray freeze granulation stage and the drying stage are sequentially performed, and the entire vacuum spray freeze-drying process can be controlled by a control system composed of a programmable logic controller and a computer.

Example 2

As shown in FIG. 3, it is a schematic structural view of the vacuum spray freeze-drying apparatus in Embodiment 2. The vacuum spray freeze-drying apparatus is similar to Embodiment 1, except that the condensation apparatus is provided in the container 1 a condenser 30 connected to the container 1 , the condenser 30 is connected to the connection port of the container 1 through a pipe 11 , and the vacuum pump 10 is connected to the condenser 30 through another pipe, A valve 12 is disposed on the pipe 11 between the condenser 30 and the connection port of the container 1, and the outer side of the upper portion of the container 1 is not provided with the cooling jacket 3.

For example, an aqueous solution of ivy powder obtained by dissolving 125 g of ivy powder in 2 L of water is used. When the apparatus is used, the steps are similar to those of the embodiment 1, except that:

Step 1: In the vacuum spray freeze granulation stage, the condenser 30 is used to condense the vaporized vapor to maintain the degree of vacuum in the container 1;

Step 2: In the drying stage, the sublimation water vapor is condensed using the condenser 30 to remove moisture in the frozen formed particles.

Example 3

As shown in FIG. 4, it is a schematic structural diagram of the vacuum spray freeze-drying apparatus in Embodiment 3, the true The air spray freeze drying apparatus is similar to the embodiment 1, except that the condensing device is a combination of the cooling jacket 3 and the condenser 30, and the cooling jacket 3 is disposed outside the upper portion of the container 1, The condenser 30 is disposed outside the container 1, the condenser 30 is connected to the connection port of the container 1 through a pipe 11, and the vacuum pump 10 is connected to the condenser 30 through another pipe. A valve 12 is disposed on the pipe 11 between the condenser 30 and the connection port of the container 1.

Step 1: In the vacuum spray freezing granulation stage, the cooling jacket 3 and the condenser 30 cooperate to coagulate the vaporized vapor to maintain the degree of vacuum in the container 1;

Step 2: In the drying stage, the cooling jacket 3 and the condenser 30 cooperate to coagulate the sublimated water vapor to remove the moisture in the frozen formed particles.

Claims

A vacuum spray freeze-drying apparatus, comprising: a closed container (1) for accommodating materials in a vacuum spray freeze-drying process; for atomizing and dispersing a liquid to be lyophilized into droplets and spraying the same The atomizing nozzle (2) in the container; for forming a vacuum environment in the container in the vacuum spray freezing granulation stage, vaporizing some of the components in the liquid droplets to cause the droplets to cool and freeze to form particles, And maintaining a vacuum system of the vacuum environment during the drying phase; and for cooling in a vacuum spray freeze granulation stage to avoid partial melting of the components in the particles and providing a portion of the particles in the drying stage Divided sublimation heat thermostat jacket (6).
A vacuum spray freeze-drying apparatus according to claim 1, further comprising: condensing a portion of said droplets after vaporization in a vacuum spray freeze granulation stage and/or sublimating in a drying stage a condensing device for condensing a portion of the particles in the granules; the vessel is provided with a means for rotating in a vacuum spray freeze granulation stage to prevent the freezing formed particles from agglomerating into ice, and in the drying stage Rotating a paddle (16) that causes the particles to tumbling up and down to exchange heat with the inner wall of the container and to allow sublimation gas to escape from the gap between the particles, the agitating paddle (16) being located in the container (1) Lower part.
A vacuum spray freeze-drying apparatus according to claim 2, wherein said condensing means is one or a combination of a cooling jacket (3) and a condenser (30), said refrigeration jacket ( 3) disposed outside the upper portion of the container (1), the inside of the cooling jacket (3) is provided with a refrigerant, and the condenser (30) is disposed outside the container (1), and The container (1) is connected.
A vacuum spray freeze-drying apparatus according to claim 3, wherein said vacuum system comprises a vacuum pump (10), said container (1) is provided with a connection port; and when said condensing device is a first refrigeration In the case of the jacket (3), the vacuum pump (10) is connected to the connection port of the container (1) through a pipe (11), and the pipe (11) is provided with a valve (12); When the condensing device is a condenser (30) or a combination of a first cooling jacket (3) and a condenser (30), the condenser (30) connects the connection of the container (1) through a pipe (11) The vacuum pump (10) is connected to the condenser (30) through another pipe, and the pipe (11) between the condenser (30) and the connection port of the container (1) is provided with a valve. (12).
The vacuum spray freeze-drying apparatus according to claim 3, wherein said refrigerating jacket (3) has a refrigerant inlet and a refrigerant outlet, and said refrigerant inlet and said refrigerant outlet are respectively connected to both ends of the refrigerant circulation line. The refrigerant circulation line is provided with a fluid pump (4) and for lowering the refrigerant a warm heat exchanger (5); the temperature regulating jacket (6) is provided with a temperature regulating fluid, and the temperature regulating jacket (6) has a temperature regulating fluid inlet and a temperature regulating fluid outlet, The temperature regulating fluid inlet and the temperature regulating fluid outlet are respectively connected to two ends of the temperature regulating fluid circulation pipeline, wherein the temperature regulating fluid circulation pipeline is provided with a fluid pump (4) and a heat exchanger for adjusting the temperature of the temperature regulating fluid ( 5) and heater (17).
A vacuum spray freeze-drying apparatus according to claim 2, characterized in that said stirring paddle (16) is connected to the motor (7) via a connecting shaft.
A vacuum spray freeze-drying apparatus according to claim 1 or 2, wherein a part of said droplets is water, and a part of said particles is ice.
A vacuum spray freeze-drying apparatus according to claim 1 or 2, wherein said liquid droplets are not in direct contact with the refrigerant in the container (1).
A vacuum spray freeze-drying apparatus according to claim 1 or 2, wherein said atomizing nozzle (2) is connected to a closed liquid dispensing pipe (8), and said liquid dispensing pipe (8) is provided Pipe flow regulating valve (9).
A vacuum spray freeze-drying apparatus according to claim 1 or 2, characterized in that the bottom of the container (1) is provided with a discharge valve (14) for discharging dry particles.
A vacuum spray freeze granulation method, characterized in that the vacuum spray freeze-drying apparatus according to any one of claims 2 to 10, comprising:

Step 1: Vacuum spray freeze granulation stage: firstly, the closed container is evacuated to a certain degree of vacuum by a vacuum system, and then the liquid to be lyophilized is atomized and dispersed into droplets and sprayed into the container by using an atomizing nozzle. Some of the components of the droplets vaporize and absorb heat in a vacuum environment to lower the temperature of the droplets, and the condensing device condenses a portion of the vaporized droplets to maintain the contents of the container The degree of vacuum, the temperature of the droplet continues to drop until freezing forms particles, and the temperature-regulating jacket is cooled at this stage to prevent the ice in the frozen formed particles from melting, and the stirring paddle is rotated to avoid the freezing. The formed particles agglomerate into ice cubes;

Step 2: Drying stage: spray freeze granulation is finished, the vacuum system is continuously evacuated to maintain the degree of vacuum in the vessel, and then the temperature-regulating jacket is heated to provide sublimation heat of some components in the pellet The continuous rotation of the stirring paddle causes the frozen formed particles to roll up and down to fully and uniformly exchange heat with the container wall, and the sublimation gas escapes from the gap between the particles, and then is condensed by the condensation device until the material is completed. Dry

Step 3: After the material is dried, a dry clean sterile gas is introduced into the closed container to balance the pressure, and the dried material is collected.