A dynamic granulation low temperature drying method and system

Abstract

This invention provides a dynamic granulation and low-temperature drying method and system. The method includes: pre-cooling a drying tower; adding liquid nitrogen into the drying tower, atomizing the pharmaceutical solution and spraying it into the liquid nitrogen to form microspheres of ice; introducing low-temperature drying gas into the drying tower, where the microspheres of ice contact the low-temperature drying gas and undergo atmospheric pressure drying; and collecting the dried solid particles. The atmospheric pressure drying process includes multiple temperature control stages, each controlling the drying tower temperature, inlet air temperature, and inlet air humidity, and monitoring the exhaust air humidity. When the exhaust air humidity decreases to a preset value, the process proceeds to the next stage. By introducing low-temperature drying gas into the drying tower, the microspheres of ice are allowed to fully contact the drying gas under atmospheric pressure for dynamic drying, improving mass transfer efficiency and reducing energy consumption. Simultaneously, a multi-stage temperature control strategy is employed, controlling the parameters of each stage and monitoring the exhaust air humidity to ensure a smooth drying process and product stability.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical equipment technology, and in particular to a dynamic granulation low-temperature drying method and system. Background Technology

[0002] Traditional freeze-drying processes typically treat granulation and drying as two separate steps, using separate equipment. Specifically, the material is first rapidly frozen into frozen granules using liquid nitrogen in a cryogenic granulation unit. These granules then need to be stored and transported at low temperatures before finally being transferred to a freeze dryer for further drying. This process has several drawbacks: Firstly, the low-temperature storage and transport steps after cryogenic granulation increase the complexity of the process, placing stringent requirements on the operating environment and equipment, making implementation difficult and cumbersome. Furthermore, temperature fluctuations during transport can easily occur, affecting product quality. Secondly, the material is exposed to the environment during transport, increasing the risk of contamination and hindering quality control in aseptic production.

[0003] Furthermore, traditional freeze-drying equipment employs static sublimation drying under extreme vacuum conditions. In this mode, frozen particles are placed statically in a drying tray, and moisture diffuses slowly from the particle surface solely through natural sublimation. This results in extremely low drying efficiency, typically requiring tens of hours or even days to complete the drying process, leading to enormous energy consumption. More importantly, due to the lack of dynamic gas-solid contact and mass transfer processes, particles obtained through static sublimation drying often exhibit a dense, non-spatial structure with an uneven microstructure, prone to stratification with a dense surface and a loose interior. This microstructural defect severely affects the rehydration performance, stability, and bioactivity of the product, failing to meet the quality standards of high-end bioproducts with specific microstructural requirements. Therefore, there is an urgent need to develop a novel freeze-drying technology that integrates granulation and drying, possesses high-efficiency mass transfer capabilities, and can obtain a uniform porous microstructure. Summary of the Invention

[0004] The purpose of this invention is to solve the problems of drying heat-sensitive materials and achieving granular spherical honeycomb porous structures in the prior art.

[0005] A first aspect of the present invention provides a dynamic granulation low-temperature drying method, comprising: The drying tower is pre-cooled to reduce its temperature. Liquid nitrogen is added into the drying tower, and the drug solution is atomized and sprayed into the liquid nitrogen to form microsphere ice particles; Low-temperature drying gas is introduced into the drying tower, and the microsphere ice particles come into contact with the low-temperature drying gas and are dried at normal pressure. Collect the dried solid particles; The atmospheric pressure drying process includes multiple temperature control stages. Each temperature control stage controls the drying tower temperature, inlet air temperature, and inlet air humidity, and monitors the exhaust air humidity. When the exhaust air humidity decreases to a preset value, the process proceeds to the next stage.

[0006] Furthermore, the pre-cooling of the drying tower includes: introducing low-temperature gas that has undergone vaporization, buffering, pressure reduction, temperature control and filtration into the drying tower, and stopping the air intake when the outlet temperature of the drying tower drops to -40℃~-60℃.

[0007] Furthermore, the liquid medicine is sprayed into liquid nitrogen through an atomizing element located inside the drying tower, and the atomizing element maintains a preset distance from the liquid nitrogen level inside the drying tower.

[0008] Furthermore, the low-temperature drying gas is tangentially introduced from the bottom of the drying tower, causing the microsphere ice particles to be in a turbulent state, thereby increasing the contact area between the microsphere ice particles and the low-temperature drying gas.

[0009] Furthermore, the low-temperature drying gas is a low-temperature insulated gas, obtained by vaporizing liquid nitrogen and then buffering, depressurizing, temperature controlling and filtering.

[0010] Furthermore, the low-temperature drying gas is circulated back into the drying tower after undergoing gas-solid separation, drying and dehydration, temperature control and filtration, forming a closed-loop system.

[0011] Furthermore, in the atmospheric pressure drying process, the initial air inlet temperature is Te-10℃~Te-20℃, where Te is the eutectic point temperature of the material; During the multiple temperature control stages, the inlet air temperature gradually increases from the initial inlet air temperature to room temperature.

[0012] Furthermore, the heating control stage includes at least three stages, and in each heating control stage, the inlet air temperature is increased by 5 to 15°C based on the inlet air temperature of the previous heating control stage. The temperature of the drying tower is the inlet air temperature +5℃ to +10℃ of the current temperature rise control stage.

[0013] Furthermore, the intake air humidity is less than 1% in each temperature control stage, and the preset value of the exhaust air humidity is 3-8%.

[0014] A second aspect of the present invention provides a dynamic granulation low-temperature drying system, employing the dynamic granulation low-temperature drying method as described in any of the preceding claims, comprising: Drying tower, wherein the bottom of the drying tower is provided with a tangential air inlet structure; The precooling unit introduces the treated low-temperature gas into the drying tower and precools the drying tower through a circulating refrigeration pipeline. A liquid nitrogen supply unit is used to add liquid nitrogen into the drying tower; The atomization unit includes a liquid atomizing component, which is located inside the drying tower and positioned at a preset distance above the liquid nitrogen level, for atomizing the liquid medicine and spraying it into the liquid nitrogen to form microsphere ice particles. A drying gas circulation unit is used to introduce low-temperature drying gas into the drying tower, so that the microsphere ice particles come into contact with the low-temperature drying gas and are dried at normal pressure. The temperature and humidity control unit is used to control the temperature rise in multiple stages during the drying process. At each stage, it controls the temperature of the drying tower, the inlet air temperature and the inlet air humidity, and monitors the exhaust air humidity. Collection unit, used to collect dried solid particles.

[0015] Compared to existing technologies, this invention offers at least the following advantages: By integrating granulation and drying processes within the same drying tower, it eliminates the need for cryogenic storage and transfer after cryogenic granulation, simplifying the process and reducing operational difficulty and contamination risks. By introducing cryogenic drying gas into the drying tower, the microsphere ice particles undergo dynamic drying under normal pressure through full contact with the drying gas. Compared to traditional extreme vacuum static sublimation drying, this improves mass transfer efficiency, shortens drying time, and reduces energy consumption. Furthermore, a multi-stage temperature control strategy is employed. By precisely controlling the drying tower temperature, inlet air temperature, and inlet air humidity at each stage, and monitoring the exhaust air humidity in real time as a basis for stage transitions, the drying process proceeds smoothly, ensuring product stability. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0017] Figure 1 This is a schematic flowchart of a dynamic granulation and low-temperature drying method in one embodiment of the present invention; Figure 2 This is a schematic diagram of the structure of a dynamic granulation low-temperature drying system in one embodiment of the present invention; Among them, 1-Liquid nitrogen inlet shut-off valve; 2-Liquid nitrogen vaporizer; 3-Gas nitrogen inlet shut-off valve; 4-Nitrogen buffer tank; 5-Drain valve; 6-Safety valve; 7-Buffer tank pressure gauge; 8-Self-regulating pressure regulating valve; 9-Post pressure gauge; 10-Gas nitrogen precision temperature control electric heater; 11-Circulating gas nitrogen dehumidifier; 12-Circulating gas nitrogen temperature control heat exchanger; 13-Closed-loop system switching valve; 14-Open system switching valve; 15-Gas nitrogen precision filter; 16-Inlet air humidity sensor; 17-Inlet air pressure sensor; 18-Liquid nitrogen level switch; 19-Gas nitrogen cooling heat exchanger jacket TCU; 20- 21-Inlet airflow regulating valve; 22-Inlet air velocity meter; 23-Inlet air temperature sensor; 24-Inlet air switch valve; 25-Pelletizing liquid nitrogen inlet valve; 26-Liquid nitrogen tank; 27-Feeding peristaltic pump; 28-Medicine liquid tank bottom valve; 29-Medicine liquid tank; 30-Drying tower; 31-Drying tower jacket temperature control TCU; 32-Cyclone separator; 33-Exhaust air humidity sensor; 34-Exhaust air temperature sensor; 35-Exhaust air closed-loop switching valve; 36-Exhaust air open switching valve; 37-Cyclone material collection valve; 38-Medicine liquid atomizing nozzle; 39-Drying tower internal temperature sensor. Detailed Implementation

[0018] The present invention will now be described in more detail with reference to the accompanying drawings, which illustrate preferred embodiments of the invention. It should be understood that those skilled in the art can modify the invention described herein while still achieving its advantageous effects. Therefore, the following description should be understood as being broadly known to those skilled in the art and is not intended to limit the invention.

[0019] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0020] The invention is described more specifically by way of example in the following paragraphs with reference to the accompanying drawings. The advantages and features of the invention will become clearer from the following description. It should be noted that the drawings are in a very simplified form and use non-precise proportions, and are only used to facilitate and clarify the illustration of the embodiments of the invention.

[0021] Example 1 In a first aspect, the present invention provides a dynamic granulation and low-temperature drying method, please refer to [reference needed]. Figure 1 and Figure 2 ,include: The drying tower is pre-cooled to lower its temperature.

[0022] Liquid nitrogen is added to the drying tower, and the drug solution is atomized and sprayed into the liquid nitrogen to form microsphere ice particles.

[0023] Low-temperature drying gas is introduced into the drying tower, and the microsphere ice particles come into contact with the low-temperature drying gas and are dried at normal pressure.

[0024] Collect the dried solid particles.

[0025] The atmospheric pressure drying process includes multiple temperature control stages. Each temperature control stage controls the drying tower temperature, inlet air temperature, and inlet air humidity, and monitors the exhaust air humidity. When the exhaust air humidity decreases to a preset value, the process proceeds to the next stage.

[0026] First, the drying tower is pre-cooled to provide a stable low-temperature environment for subsequent low-temperature granulation and drying. Then, liquid nitrogen is added to the drying tower, and the drug solution is atomized and precisely sprayed into the liquid nitrogen. The ultra-low temperature properties of liquid nitrogen cause the droplets to freeze instantly into uniform microsphere ice particles, avoiding solute stratification and particle agglomeration. Next, low-temperature drying gas is introduced into the tower. The microsphere ice particles are in full contact with the gas in a turbulent state. Moisture is gradually removed through a multi-stage gradient heating atmospheric pressure sublimation drying method. Each stage is automatically switched by monitoring the exhaust humidity, which ensures that the ice particles do not melt, the activity of heat-sensitive materials is not lost, and the drying efficiency is improved. Finally, spherical, porous honeycomb-shaped dried particles are collected, which have high specific surface area and good resolubility.

[0027] Furthermore, the pre-cooling of the drying tower includes: introducing low-temperature gas that has undergone vaporization, buffering, pressure reduction, temperature control and filtration into the drying tower, and stopping the air intake when the outlet temperature of the drying tower drops to -40℃~-60℃.

[0028] Specifically, a temperature sensor is installed at the outlet of the drying tower to monitor the exhaust temperature inside the tower in real time. This sensor transmits the monitored temperature signal to the control system. When the control system detects that the outlet temperature of the drying tower reaches the preset range of -40°C to -60°C, it issues a command to close the inlet valve of the cryogenic gas or stop the supply of cryogenic gas, thereby terminating the pre-cooling process. This temperature range is set based on optimized considerations of the drug atomization and microsphere ice particle formation process, ensuring that the internal environment of the drying tower reaches the optimal initial low temperature state to promote rapid freezing of the drug into uniform microsphere ice particles and provide stable starting conditions for the subsequent atmospheric pressure drying stage. Preferably, the monitoring temperature for stopping the air intake is -50°C.

[0029] Furthermore, the liquid medicine is sprayed into liquid nitrogen through an atomizing element located inside the drying tower, and the atomizing element maintains a preset distance from the liquid nitrogen level inside the drying tower.

[0030] The function of the atomizing element is to disperse the liquid medicine into fine droplets, thereby increasing the surface area and promoting rapid heat exchange with liquid nitrogen, which in turn rapidly freezes the liquid into microspheres of ice. Atomizing elements can take various forms, such as pressure nozzles, two-fluid nozzles, ultrasonic atomizers, or rotary disc atomizers. Pressure nozzles use high pressure to force the liquid medicine through fine pores to form droplets; two-fluid nozzles use high-speed airflow to shear the liquid medicine into droplets; ultrasonic atomizers use high-frequency vibration to create standing waves on the liquid surface and form droplets; and rotary disc atomizers use a high-speed rotating disc to fling the liquid medicine out to form droplets. The choice of these atomization methods depends on factors such as the properties of the liquid medicine (e.g., viscosity, surface tension), the required microsphere ice particle size, and the production scale.

[0031] Maintaining a predetermined distance between the atomizing element and the liquid nitrogen level requires comprehensive consideration of the atomization characteristics of the drug, the evaporation rate of the liquid nitrogen, and the formation process of the microsphere ice particles. If the distance is too close, the atomized droplets may come into contact with the liquid nitrogen before they are fully dispersed, leading to droplet aggregation or uneven freezing. If the distance is too far, the atomized droplets may be affected by air resistance and temperature changes during their descent, causing some droplets to evaporate, crystallize, or collide and aggregate before contacting the liquid nitrogen, thus affecting the uniformity and particle size of the microsphere ice particles. The predetermined distance is usually determined through experimental optimization to achieve the best atomization effect and microsphere ice particle quality. This distance can be a fixed value or a range that is dynamically adjusted according to process parameters (such as drug flow rate and liquid nitrogen level fluctuations).

[0032] Furthermore, the low-temperature drying gas is tangentially introduced from the bottom of the drying tower, causing the microsphere ice particles to be in a turbulent state, thereby increasing the contact area between the microsphere ice particles and the low-temperature drying gas.

[0033] Specifically, "tangential introduction" refers to the low-temperature drying gas entering the drying tower not vertically or radially, but tangentially to the inner wall of the drying tower. Its function is to give the incoming airflow a rotational component, thus creating a spiraling, upward-moving vortex field inside the drying tower. Based on this, "turbulent state" refers to the irregular, random, and violent motion of the microsphere ice particles within the drying tower as the tangentially introduced low-temperature drying gas flows. In this state, the microsphere ice particles no longer simply settle or rise steadily with the airflow, but are driven by the airflow, undergoing thorough mixing and tumbling within the drying tower space. This motion helps break up particle agglomeration and ensures frequent contact between each particle and fresh drying gas. By tangentially introducing gas to create turbulence in the microsphere ice particles, the surface area exposed to the low-temperature drying gas for each microsphere ice particle is increased. Under turbulent action, the particles are fully dispersed, avoiding particle accumulation or airflow short-circuiting, allowing the gas to uniformly surround and penetrate each particle, maximizing mass and heat transfer efficiency.

[0034] Furthermore, the low-temperature drying gas is a low-temperature insulated gas, obtained by vaporizing liquid nitrogen and then buffering, depressurizing, temperature controlling and filtering.

[0035] Specifically, the cryogenic oven-dry gas refers to a gas with extremely low moisture content and high dryness. This gas is crucial for the cryogenic drying process, effectively preventing the introduction of additional moisture during drying. This allows for the efficient removal of moisture from the microsphere ice particles, preventing the product from deliquescence or clumping during drying. This cryogenic oven-dry gas is obtained through the vaporization of liquid nitrogen. Liquid nitrogen, vaporized at room temperature or through controlled heating, produces a large amount of pure, extremely dry nitrogen gas. This vaporization process itself provides a natural, high-purity source of dry gas, avoiding impurities and moisture that may be introduced during traditional air drying or dehumidification processes.

[0036] Furthermore, the low-temperature drying gas is circulated back into the drying tower after undergoing gas-solid separation, drying and dehydration, temperature control and filtration, forming a closed-loop system.

[0037] The used low-temperature drying gas undergoes gas-solid separation, drying to remove moisture, temperature control, and filtration before being recirculated back into the drying tower, forming a closed-loop system. This design allows for the efficient reuse of the low-temperature drying gas, reducing the demand for fresh gas. Given that low-temperature drying gas is typically derived from liquid nitrogen vaporization, its production cost is high; the closed-loop system significantly reduces operating costs and improves energy efficiency. Simultaneously, the rigorous gas-solid separation, drying to remove moisture, and filtration processes ensure that the gas entering the drying tower maintains the required low humidity and high cleanliness, crucial for maintaining the drying effect and product quality of the microsphere ice particles. Furthermore, this system avoids the direct emission of waste gas containing moisture or trace particles into the environment, reducing environmental pollution and meeting the requirements of green production. Overall, the closed-loop system not only improves the economy and environmental friendliness of the drying process but also provides stable gas conditions for precise multi-stage temperature control, thereby optimizing the performance of the entire dynamic granulation low-temperature drying method.

[0038] Furthermore, in the atmospheric pressure drying process, the initial air inlet temperature is Te-10℃~Te-20℃, where Te is the eutectic point temperature of the material.

[0039] Specifically, the eutectic point temperature (Te) of the material refers to the lowest temperature at which ice crystals and solute crystals coexist during the freezing process of the drug solution. Setting the initial inlet air temperature within the range of Te-10℃ to Te-20℃, slightly lower than the eutectic point temperature of the material, aims to ensure that the microsphere ice particles remain completely frozen in the initial stage of the drying process. This effectively avoids localized melting of ice crystals due to excessively high initial temperatures, which would damage the internal structure of the microsphere ice particles, thus maintaining their morphological integrity and the stability of the active ingredients. Achieving this temperature control typically requires configuring high-precision temperature sensors, heating / cooling devices, and a corresponding PID control system to ensure that the low-temperature drying gas is stably maintained within the target temperature range.

[0040] In the multiple temperature control stages, the inlet air temperature gradually increases from the initial inlet air temperature towards room temperature. This gradual temperature increase strategy aims to provide a continuous and gradually increasing energy input for the sublimation drying process of the microsphere ice particles, while avoiding thermal stress or localized overheating caused by sudden temperature changes. As drying progresses, the ice crystal content in the microsphere ice particles gradually decreases, and the structural strength and temperature tolerance of the material change. By increasing the temperature in stages and in small increments, the water sublimation rate can be optimized, the overall drying time can be shortened, and the activity and structure of the material can be protected to the greatest extent.

[0041] Furthermore, the temperature control stage includes at least three stages, and in each stage the inlet air temperature is increased by 5 to 15°C based on the inlet air temperature of the previous stage.

[0042] The temperature of the drying tower is the inlet air temperature +5℃ to +10℃ of the current temperature rise control stage.

[0043] Furthermore, the intake air humidity is less than 1% in each temperature control stage, and the preset value of the exhaust air humidity is 3-8%.

[0044] By setting at least three stages, targeted temperature control can be implemented based on the characteristics of the material at different drying stages (e.g., surface moisture removal, internal moisture diffusion, and bound water removal), avoiding the problem of inefficient temperature control that may result from using only one or a few stages. For example, a lower temperature can be used in the initial stage to gently remove surface moisture, the temperature can be gradually increased in subsequent stages to accelerate the migration of internal moisture, and the final stage can be used for deep drying to ensure that the final moisture content of the material meets the standard. Meanwhile, the inlet air temperature is set to increase sequentially by 5-15°C in each temperature control stage to avoid impact on the microsphere ice particles caused by sudden temperature rises, thereby effectively preventing the material from melting, degrading, or structurally damaging. For example, for heat-sensitive materials, a smaller temperature increase (e.g., 5°C) can be selected to maximize the protection of their active ingredients; while for materials with better thermal stability, a larger temperature increase (e.g., 15°C) can be selected to improve drying efficiency. This flexible and controlled temperature increase strategy helps maintain the integrity and efficacy of the microsphere ice particles.

[0045] Furthermore, the drying tower temperature is precisely controlled to be between 5°C and 10°C above the inlet air temperature during the current heating control phase. This setting establishes a synergistic relationship between the internal ambient temperature of the drying tower and the temperature of the drying gas entering the tower. By maintaining the drying tower temperature slightly higher than the inlet air temperature, condensation on the tower walls due to excessively low inlet air temperatures is prevented. Simultaneously, a stable drying environment slightly above the inlet air temperature is provided for the microsphere ice particles, promoting efficient heat transfer from the gas to the material. This temperature difference design helps maintain the uniformity of the temperature field within the drying tower, avoiding localized overheating or undercooling, thereby ensuring uniform heating of the microsphere ice particles throughout the drying process and improving drying quality.

[0046] Example 2 The second aspect of the present invention is described in reference to... Figure 2 A dynamic granulation low-temperature drying system is provided, employing the dynamic granulation low-temperature drying method as described in Example 1, comprising: Drying tower 29, the bottom of which is provided with a tangential air inlet structure.

[0047] The precooling unit introduces the treated low-temperature gas into the drying tower 29 and precools the drying tower 29 through a circulating refrigeration pipeline.

[0048] A liquid nitrogen supply unit is used to add liquid nitrogen into the drying tower 29.

[0049] The atomization unit includes a liquid atomizing element, which is located inside the drying tower 29 and positioned at a preset distance above the liquid nitrogen level. It is used to atomize the liquid medicine and spray it into the liquid nitrogen to form microsphere ice particles.

[0050] The drying gas circulation unit is used to introduce low-temperature drying gas into the drying tower 29, so that the microsphere ice particles come into contact with the low-temperature drying gas and are dried at normal pressure.

[0051] The temperature and humidity control unit is used to control the temperature rise in multiple stages during the drying process. In each stage, it controls the temperature of the drying tower 29, the inlet air temperature and the inlet air humidity, and monitors the exhaust air humidity.

[0052] Collection unit, used to collect dried solid particles.

[0053] The dynamic granulation low-temperature drying system will be explained below with reference to the dynamic granulation low-temperature drying method in Example 1, using specific implementation methods: First, the system is cooled down. After the equipment is fully connected and in standby mode, the following operations are performed: the drying tower jacket temperature control TCU30 is started to circulate and cool the jacket of the drying tower 29. Liquid nitrogen enters the liquid nitrogen vaporizer 2 through the liquid nitrogen inlet shut-off valve 1 and is vaporized into low-temperature gaseous nitrogen. It then enters the nitrogen buffer tank 4 through the gaseous nitrogen inlet shut-off valve 3 for buffering. The nitrogen buffer tank 4 is equipped with a drain valve 5 and a safety valve 6.

[0054] Pressure gauge 7 in the buffer tank monitors the nitrogen pressure inside the tank, self-regulating pressure valve 8 reduces pressure, and pressure gauge 9 reflects the pressure value after regulation. Precision nitrogen temperature control electric heater 10 controls the temperature. The low-temperature nitrogen passes through closed-loop circulation system switching valve 13 and is filtered by nitrogen precision filter 15, with the flow rate controlled by inlet air volume regulating valve 20, entering the drying tower 29 tangentially from the bottom. Gas-solid separation occurs from the exhaust pipe via cyclone separator 31, with the gas exiting through open exhaust switching valve 36 to form an open system or entering the circulation pipeline through closed exhaust circulation switching valve 35. Before exhaust, humidity, temperature, and pressure are detected by exhaust humidity sensor 32, exhaust temperature sensor 33, and exhaust pressure sensor 34, respectively.

[0055] The internal cooling system of the drying tower is achieved through a closed-loop circulation system: the air is dried and dehumidified by a circulating nitrogen dehumidifier 11, cooled by a circulating nitrogen temperature-controlled heat exchanger 12, and filtered by an open system switching valve 14 and a nitrogen precision filter 15. In this embodiment, temperature monitoring is performed using a temperature sensor 39 inside the drying tower in conjunction with a temperature sensor at the drying tower outlet. When the outlet temperature reaches -50°C, air intake is stopped, and preparation is made for adding liquid nitrogen. The following steps are based on the closed-loop circulation scheme.

[0056] Liquid nitrogen is added into the drying tower 29 through the liquid nitrogen tank 25 and the granulation liquid nitrogen inlet valve 24. The granulation liquid nitrogen inlet valve 24 is linked with the liquid nitrogen level switch 18 to control the liquid nitrogen level. The chemical solution is supplied from the chemical solution tank 28 through the chemical solution tank bottom valve 27 to the feeding peristaltic pump 26. The feeding pipe is connected to the chemical solution atomizing nozzle 38, which is located inside the drying tower 29 and positioned at a certain distance above the liquid nitrogen level to achieve atomized cryogenic granulation.

[0057] After granulation, shut off the peristaltic pump 26 to stop feeding, close the liquid nitrogen inlet valve 24 to stop liquid nitrogen supply, remove the liquid atomizing nozzle 38 and the liquid nitrogen inlet pipeline, seal their installation ports with a special plug, and keep the exhaust port at the top of the tower unobstructed. During the cold air drying stage: liquid nitrogen passes through the liquid nitrogen inlet shut-off valve 1 and is vaporized into low-temperature gaseous nitrogen by the liquid nitrogen vaporizer 2. This gaseous nitrogen is then buffered by the nitrogen buffer tank 4, pressure is reduced by the self-regulating pressure regulating valve 8, and temperature is controlled by the gaseous nitrogen precision temperature control electric heater 10. The gaseous nitrogen then passes through the closed-loop system switching valve 13 and is filtered by the gaseous nitrogen precision filter 15. The airflow regulating valve 20 controls the flow rate. The air enters the drying tower 29 tangentially from the bottom. It passes through the cyclone separator 31 for gas-solid separation via the exhaust pipe. The gas then enters the circulation pipeline via the closed-loop exhaust switching valve 35 and is dried by the circulating nitrogen dehumidifier 11. The circulating nitrogen temperature control heat exchanger 12 is used for cooling and temperature control. The gas then enters the nitrogen precision filter 15 via the open system switching valve 14 for filtration. The airflow is regulated by the inlet air volume regulating valve 20. The air then enters the drying tower 29 tangentially from the bottom inlet. The tangential air inlet filter acts on the ice particles, creating turbulence and allowing for full contact with the cold, dry air. This achieves atmospheric pressure sublimation freeze-drying of the ice particles, removing moisture. The water-laden nitrogen then enters the circulation pipeline from the exhaust pipe via the cyclone separator 31 and a dry powder filter, achieving closed-loop nitrogen circulation for cold air atmospheric pressure freeze-drying of the tower material.

[0058] The system is equipped with an inlet anemometer 21 to detect inlet air velocity, an inlet air humidity sensor 16 to detect inlet air humidity, an inlet air temperature sensor 22 to detect inlet air temperature, and an inlet air pressure sensor 17 to detect inlet air pressure. These sensors ensure the normal operation of the system and the monitoring of various indicators during the material drying process, and facilitate the switching of material drying stages. The inlet air state is controlled and switched via an inlet air switch valve 23. A gas-nitrogen cooling heat exchanger jacket TCU19 controls the cooling and temperature of the circulating gas-nitrogen temperature control heat exchanger 12.

[0059] Material drying and powder collection: The inlet air temperature is related to the eutectic point temperature of the material. Generally, the initial inlet air temperature is about 10°C lower than the eutectic point temperature of the material.

[0060] Taking material A with a eutectic point temperature of -30℃ as an example: the air intake volume throughout the process is set to the minimum flow rate that can form turbulent boiling state inside the equipment. This ensures that the material is in full contact with the cold air and prevents the material from entering the back end too early with the cold air, thus maintaining continuous operation of the system. During the process, the system pressure is monitored and nitrogen is automatically replenished and discharged.

[0061] Stage 01: The equipment jacket temperature is controlled to -35℃, the air inlet humidity device is controlled to a moisture content of less than 1%, the air inlet temperature is controlled to -40℃, and the humidity sensor value after the cyclone is detected. When the exhaust moisture content drops to about 5%, it enters Stage 02.

[0062] Stage 02: The equipment jacket temperature is controlled to -25℃, the inlet air humidity is controlled to below 1%, the temperature is controlled to -30℃, and the humidity sensor value after the cyclone is detected. When the exhaust humidity content drops to about 5%, it enters Stage 03.

[0063] Stage 03: The equipment jacket temperature is controlled to -15℃, the inlet air humidity is controlled to below 1%, the temperature is controlled to -20℃, and the humidity sensor value after the cyclone is detected. When the exhaust humidity content drops to about 5%, it enters Stage 04.

[0064] Stage 04: The equipment jacket temperature is controlled to -5℃, the inlet air humidity is controlled to below 1%, the temperature is controlled to -10℃, and the humidity sensor value after the cyclone is detected. When the exhaust humidity content drops to about 5%, it enters Stage 05.

[0065] Stage 05: The equipment jacket temperature is controlled to 10℃, the inlet air humidity is controlled to below 1%, the temperature is controlled to 0℃, and the humidity sensor value after the cyclone is detected. When the exhaust humidity content drops to about 5%, it enters Stage 06.

[0066] Stage 06: The equipment jacket temperature is controlled to 15℃, the inlet air humidity is controlled to below 1%, the temperature is controlled to 10℃, and the humidity sensor value after the cyclone is detected. When the exhaust humidity content drops to about 5%, it enters Stage 07.

[0067] Stage 07: The equipment jacket temperature is controlled to 25℃, the inlet air humidity is controlled to below 1%, the temperature is controlled to 15℃, and the humidity sensor value after the cyclone is detected. When the exhaust humidity content drops to about 5%, it enters Stage 08.

[0068] Stage 08: The equipment jacket temperature is controlled to 35℃, the inlet air humidity is controlled to below 1%, the temperature is controlled to 25℃, and the humidity sensor value after the cyclone is detected. When the exhaust humidity content drops to about 5%, it enters Stage 09.

[0069] Stage 09: Stop air intake, take samples from the bottom of the cone to test the moisture content, and collect the material at the bottom outlet of the tower or by opening the cyclone collection valve 37. Production ends here.

[0070] The above examples illustrate the present invention only to aid in understanding it and are not intended to limit the scope of the invention. Those skilled in the art can make various simple deductions, modifications, or substitutions based on the principles of this invention.

Claims

1. A dynamic granulation and low-temperature drying method, characterized in that, include: The drying tower is pre-cooled to reduce its temperature. Liquid nitrogen is added to the drying tower, and the drug solution is atomized and sprayed into the liquid nitrogen to form microsphere ice particles; Low-temperature drying gas is introduced into the drying tower, and the microsphere ice particles come into contact with the low-temperature drying gas and are dried at normal pressure. Collect the dried solid particles; The atmospheric pressure drying process includes multiple temperature control stages. Each temperature control stage controls the drying tower temperature, inlet air temperature, and inlet air humidity, and monitors the exhaust air humidity. When the exhaust air humidity decreases to a preset value, the process proceeds to the next stage.

2. The dynamic granulation and low-temperature drying method as described in claim 1, characterized in that, The pre-cooling of the drying tower includes: introducing low-temperature gas that has undergone vaporization, buffering, pressure reduction, temperature control and filtration into the drying tower, and stopping the air intake when the outlet temperature of the drying tower drops to -40℃~-60℃.

3. The dynamic granulation and low-temperature drying method as described in claim 1, characterized in that, The liquid medicine is sprayed into liquid nitrogen through an atomizing element located inside the drying tower, and the atomizing element maintains a preset distance from the liquid nitrogen level inside the drying tower.

4. The dynamic granulation and low-temperature drying method as described in claim 1, characterized in that, The low-temperature drying gas is introduced tangentially from the bottom of the drying tower, causing the microsphere ice particles to be in a turbulent state, thereby increasing the contact area between the microsphere ice particles and the low-temperature drying gas.

5. The dynamic granulation and low-temperature drying method as described in claim 4, characterized in that, The low-temperature dry gas is a low-temperature insulated dry gas, which is obtained by vaporizing liquid nitrogen and then buffering, depressurizing, temperature controlling and filtering.

6. The dynamic granulation and low-temperature drying method as described in claim 5, characterized in that, The low-temperature drying gas is circulated back into the drying tower after gas-solid separation, drying and dehydration, temperature control and filtration, forming a closed-loop system.

7. The dynamic granulation and low-temperature drying method as described in claim 1, characterized in that, In the atmospheric pressure drying process, the initial air inlet temperature is Te-10℃~Te-20℃, where Te is the eutectic point temperature of the material. During the multiple temperature control stages, the inlet air temperature gradually increases from the initial inlet air temperature to room temperature.

8. The dynamic granulation and low-temperature drying method as described in claim 7, characterized in that, The heating control stage includes at least three stages, and in each heating control stage, the inlet air temperature is increased by 5 to 15°C based on the inlet air temperature of the previous heating control stage. The temperature of the drying tower is the inlet air temperature +5℃ to +10℃ of the current temperature rise control stage.

9. The dynamic granulation and low-temperature drying method as described in claim 8, characterized in that, The intake air humidity is less than 1% in each temperature control stage, and the preset value of the exhaust air humidity is 3-8%.

10. A dynamic granulation low-temperature drying system, characterized in that, The dynamic granulation and low-temperature drying method according to any one of claims 1-9 includes: Drying tower, wherein the bottom of the drying tower is provided with a tangential air inlet structure; The precooling unit introduces the treated low-temperature gas into the drying tower and precools the drying tower through a circulating refrigeration pipeline. A liquid nitrogen supply unit is used to add liquid nitrogen into the drying tower; The atomization unit includes a liquid atomizing element, which is located inside the drying tower and positioned at a preset distance above the liquid nitrogen level, for atomizing the liquid medicine and spraying it into the liquid nitrogen to form microsphere ice particles. A drying gas circulation unit is used to introduce low-temperature drying gas into the drying tower, so that the microsphere ice particles come into contact with the low-temperature drying gas and are dried at normal pressure. The temperature and humidity control unit is used to control the temperature rise in multiple stages during the drying process. At each stage, it controls the temperature of the drying tower, the inlet air temperature and the inlet air humidity, and monitors the exhaust air humidity. Collection unit, used to collect dried solid particles.

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