Experimental atomization freeze device and method of operation

Abstract

This invention relates to an experimental atomizing and freezing device and its operating method, comprising an atomizing and freezing tower mounting bracket, an atomizing and freezing tower, a balance cylinder assembly, a support platform, a moving feed / discharge assembly, a positioning fixture, and a refrigeration unit. The atomizing and freezing tower mounting bracket is connected to the support platform, and the atomizing and freezing tower is connected to the mounting bracket. The moving feed / discharge assembly and the positioning fixture are also connected to the support platform; the moving feed / discharge assembly is used for material transfer, and the positioning fixture is used for positioning the atomizing and freezing tower. The refrigeration unit is located beside the support platform and connected to the atomizing and freezing tower. The balance cylinder assembly is connected to the atomizing and freezing tower mounting bracket and is connected to the pipe connecting the refrigeration unit and the atomizing and freezing tower. This invention allows for better control of particle size, morphology, and density, improving the consistency of formulation performance.

Description

Technical Field

[0001] This invention relates to an experimental atomizing freezing device and its operating method. Background Technology

[0002] Existing spray freeze-drying equipment uses vacuum freeze atomization of droplets. Due to the vacuum environment, some of the sprayed atomized droplets undergo sublimation and are drawn into the cold trap, resulting in some material loss. Existing spray freeze-drying equipment uses industrial nozzles, which make it difficult to produce particles smaller than 5μm. However, micro-mesh atomizing nozzles can be easily used to produce uniform atomization, with concentrated droplet size distribution, compact structure, small size, and easy integration.

[0003] Traditional lyophilized inhalation formulation production methods involve first lyophilizing the drug solution into a solid cake, then pulverizing and sorting it by particle size to obtain inhalation powder of the target particle size. The advantages of this process are relatively simple equipment requirements, flexible operation, and suitability for production at various scales. However, a disadvantage is that the pulverization process may damage the particle morphology, resulting in a wide particle size distribution and affecting inhalation performance. Therefore, to address these issues, an experimental nebulization refrigeration device and its operating method are proposed. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of existing methods by providing an experimental atomizing and freezing device and operating method, which can better control the size, shape and density of particles and improve the consistency of formulation performance.

[0005] The technical solution to achieve the above objectives is: an experimental atomizing freezing device, including an atomizing freezing tower mounting bracket, an atomizing freezing tower, a balance cylinder assembly, a support platform, a moving feed and discharge assembly, positioning fixtures, and a refrigeration unit;

[0006] The supporting platform is connected to the atomizing freezing tower mounting bracket, and the atomizing freezing tower is connected to the atomizing freezing tower mounting bracket. The supporting platform is also connected to a moving feed / discharge assembly and a positioning fixture. The moving feed / discharge assembly is used for material transfer, and the positioning fixture is used for positioning the atomizing freezing tower. The refrigeration unit is located beside the supporting platform and connected to the atomizing freezing tower. The balance cylinder assembly is connected to the atomizing freezing tower mounting bracket and connects to the pipe between the refrigeration unit and the atomizing freezing tower.

[0007] Preferably, the mobile feeding / discharging assembly includes a mobile base with a slider mounting hole for sliding connection with the support platform; a drive mechanism is connected to the mobile base, the drive mechanism is connected to a lifting bracket, the lifting bracket has a lifting bracket reinforcing rib on its front side and a lifting bracket reinforcing plate on its rear side, and a positioning hole for the bottom of the atomizing freezing tower is provided on the lifting bracket; a lifting bracket pad is provided between the drive mechanism and the lifting bracket; and a handle is provided on the rear side of the drive mechanism.

[0008] Preferably, the atomizing freezing tower includes a tower body, the inner wall of which is provided with a first refrigerant circulation jacket, an annular guide plate is provided between the first refrigerant circulation jacket and the tower body, and a tower body insulation layer is provided on the outer side of the tower body; a first refrigerant outlet is provided on the upper side of the tower body and connected to the first refrigerant circulation jacket, and a first refrigerant inlet is provided on the lower side of the tower body and connected to the first refrigerant circulation jacket; the tower body is connected to the atomizing freezing tower mounting bracket.

[0009] Preferably, the atomizing refrigeration tower further includes a tower bottom, the inner wall of which is provided with a second refrigerant circulation jacket, the upper end of the outer wall of which is provided with a second refrigerant outlet, and the lower end of the outer wall of which is provided with a second refrigerant inlet; the outer wall of which is provided with a tower bottom insulation layer; the bottom of which is connected to a discharge port; the bottom surface of which is connected to a tower bottom positioning column for connection with the lifting support; the inner wall of which is provided with a tray placement platform for placing material trays; the tray placement platform is provided with a tray removal clearance hole for easy removal of the placed material trays; the upper end of which is a sealing surface for sealing connection with the lower end of the tower body.

[0010] Preferably, the atomizing freezing tower further includes a tower cover, which is connected to the upper end of the tower body via a tower cover-tower body connector. The tower cover has a nozzle mounting port, which is connected to an atomizing nozzle assembly.

[0011] Preferably, the atomizing nozzle assembly includes a nozzle connecting fixture, on which multiple atomizing nozzles are connected, and each atomizing nozzle is connected to a power source; the lower end of the nozzle connecting fixture is connected to the nozzle mounting port via a spray assembly connecting connector.

[0012] Preferably, the positioning fixture includes a fixing block, which is fixedly connected to the support platform. The fixing block is provided with a through bolt, and the other end of the bolt is rotatably connected to a countersunk hole opened in the limiting hole; the limiting hole abuts against the bottom of the tower.

[0013] Preferably, the second refrigerant inlet at the bottom of the tower is connected to a first pipeline, on which an inlet temperature probe, a control valve, a first oil drain valve, and a tower bottom inlet valve are sequentially connected; the second refrigerant outlet is connected to the first refrigerant inlet in the tower body via a second pipeline, on which a tower bottom outlet valve and a tower body inlet valve are respectively installed; the first refrigerant outlet is connected to a third pipeline, on which a tower body outlet valve, a second oil drain valve, and an outlet temperature probe are sequentially connected, the other end of the outlet temperature probe is connected to a fourth pipeline, the other end of the fourth pipeline is connected to the refrigeration unit, and the end of the first pipeline away from the bottom of the tower is connected to the refrigeration unit.

[0014] Preferably, it also includes a tower temperature probe, which is used to detect the temperature of the tower body, the tower cover and the tower bottom.

[0015] Preferably, the tower base is connected to the lower end of the tower body via a tower body-tower base connector.

[0016] The operating method of the experimental atomizing freezing device includes the following steps:

[0017] Step 1: Install the atomizing nozzle on the top of the tower, place the material tray on the bottom of the atomizing freezing tower, push the moving feed and discharge assembly to hold the positioning fixture, use the drive mechanism to initially connect the tower bottom to the tower body, and then use clamps to lock the tower bottom and tower body together.

[0018] Step two: The circulating refrigerant is introduced from the first pipeline through the control valve and the bottom inlet valve of the tower into the second refrigerant circulation jacket at the bottom of the tower. Then, it enters the first refrigerant circulation jacket in the tower body through the second pipeline and the tower body inlet valve from the bottom outlet valve. The refrigerant flows along the annular guide plate from the tower body outlet valve into the third pipeline, and finally flows into the magnetic pump along the fourth pipeline to complete the refrigerant circulation process in the physicochemical refrigeration tower, so that the tower body reaches a suitable freezing temperature.

[0019] Step 3: Mix the drug with excipients, surfactants and other excipients to prepare a uniform solution. Pour the prepared solution into the storage tank of the atomizing nozzle, turn on the power and the nozzle to atomize the solution into the low-temperature freezing tower. After the solution is completely atomized, loosen the clamps, use the drive mechanism to separate the tower bottom from the tower body, pull the handle of the moving feed and discharge components, and then use the grippers to pick up the material tray and transfer it to the freeze dryer for sublimation drying to prepare freeze-dried granules in a low-temperature environment.

[0020] The beneficial effects of this invention are as follows: This experimental atomizing freezing device and operating method rapidly freezes droplets atomized by a micro-mesh atomizing nozzle, collects atomized frozen particles with a particle size of less than 5 μm without melting, and transfers the frozen particles to a freeze dryer for freeze drying to obtain inhalable freeze-dried particles; the non-vacuum characteristics meet the requirements of most experiments, reducing experimental difficulty and cost; the equipment is simple to operate, and the height of the atomizing freeze-drying tower can be increased according to drug or experimental needs; the atomizing function of the micro-mesh atomizing nozzle is not affected during equipment operation; in actual operation, the ambient temperature inside the tower is below -40℃, and the material collection rate of the bottom tray is high; the particle size detection result after freeze-drying is expected to be below 5 μm, suitable for inhalation; the spray freeze-drying process directly atomizes the drug solution into fine droplets, rapidly freezes them at extremely low temperatures, and then freeze-dries them, preparing porous microspheres with suitable particle size in one step. Compared with pulverization after freeze-drying, spray freeze-drying can better control the size, morphology, and density of particles, reduce losses during the pulverization process, and improve the consistency of formulation performance. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of the experimental atomizing freezing device of the present invention;

[0022] Figure 2 This is a schematic diagram of the moving feed / discharge assembly of the present invention;

[0023] Figure 3 This is a schematic diagram of the interior of the tower body of the present invention;

[0024] Figure 4 This is a schematic diagram of the interior of the tower base of the present invention;

[0025] Figure 5 This is a schematic diagram of the tower cover of the present invention;

[0026] Figure 6 This is a schematic diagram of the atomizing nozzle assembly of the present invention;

[0027] Figure 7 This is a schematic diagram of the positioning fixture of the present invention;

[0028] Figure 8 This is a schematic diagram of the refrigerant circulation in the atomizing freezing tower of the present invention.

[0029] In the diagram: 1. Lifting support; 2. Movable base; 3. Lifting support reinforcing rib; 4. Lifting support reinforcing plate; 5. Drive mechanism; 6. Handle; 7. Lifting support pad; 8. Atomizing refrigeration tower bottom positioning hole; 9. Slider mounting hole; 11. Tower body; 12. First refrigerant circulation jacket; 13. Annular guide plate; 14. Tower body insulation layer; 15. First refrigerant inlet; 16. First refrigerant outlet; 20. Tower bottom positioning column; 21. Tower bottom; 22. Second refrigerant circulation jacket; 23. Tower bottom insulation layer; 24. Second refrigerant inlet; 25. Second refrigerant outlet; 26. Discharge port; 27. Pallet removal clearance hole; 28. Sealing surface; 29. ​​Pallet placement platform; 31. Tower cover; 32. Tower cover and tower body connector; 34. Tower body and tower bottom connector; 37. Nozzle mounting port; 41. Fixing block; 42. Limiting hole; 43. Bolt; 44. Countersunk hole; 50. First pipeline; 51. Inlet temperature probe; 52. Control valve; 53. First drain valve; 54. Tower bottom inlet valve; 56. Tower bottom outlet valve; 57. Second pipeline; 58. Tower body inlet valve; 60. Tower body outlet valve; 61. Third pipeline; 62. Second drain valve; 63. Tower temperature probe; 65. Outlet temperature probe; 66. Fourth pipeline; 70. Atomizing refrigeration tower mounting bracket; 71. Atomizing refrigeration tower; 72. Atomizing nozzle assembly; 73. Balance cylinder assembly; 74. Material tray; 75. Support platform; 76. Moving feed / discharge assembly; 77. Positioning fixture; 78. Refrigeration unit; 80. Nozzle connection fixture; 81. Atomizing nozzle; 82. Power supply; 83. Spray assembly connection joint. Detailed Implementation

[0030] The technical solution of the present invention will now be clearly and completely described in conjunction with the accompanying drawings. In the description of the present invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0031] The invention will now be further described with reference to the accompanying drawings.

[0032] like Figure 1As shown, the experimental atomizing freezing device includes an atomizing freezing tower mounting bracket 70, an atomizing freezing tower 71, a balance cylinder assembly 73, a support platform 75, a moving feed / discharge assembly 76, a positioning fixture 77, and a refrigeration unit 78. The atomizing freezing tower mounting bracket 70 is connected to the support platform 75, and the atomizing freezing tower 71 is connected to the atomizing freezing tower mounting bracket 70. The moving feed / discharge assembly 76 and the positioning fixture 77 are also connected to the support platform 75. The moving feed / discharge assembly 76 is used for material transfer, and the positioning fixture 77 is used for positioning the atomizing freezing tower 71. The refrigeration unit 78 is located on one side of the support platform 75 and is connected to the atomizing freezing tower 71. The balance cylinder assembly 73 is connected to the atomizing freezing tower mounting bracket 70 and is connected between the refrigeration unit 78 and the atomizing freezing tower 71 via a pipe.

[0033] like Figure 2 As shown, the mobile infeed / outfeed assembly 76 includes a mobile base 2, on which a slider mounting hole 9 is provided for sliding connection with the support platform 75; a drive mechanism 5 is connected to the mobile base 2, and the drive mechanism 5 is connected to the lifting bracket 1. The lifting bracket 1 has a lifting bracket reinforcing rib 3 on its front side and a lifting bracket reinforcing plate 4 on its rear side. The lifting bracket 1 has an atomizing freezing tower bottom positioning hole 8; a lifting bracket pad 7 is provided between the drive mechanism 5 and the lifting bracket 1; and a handle 6 is provided on the rear side of the drive mechanism 5.

[0034] like Figure 3 As shown, the atomizing refrigeration tower 71 includes a tower body 11, a first refrigerant circulation jacket 12 is provided on the inner wall of the tower body 11, an annular guide plate 13 is provided between the first refrigerant circulation jacket 12 and the tower body 11, and a tower body insulation layer 14 is provided on the outer side of the tower body 11; a first refrigerant outlet 16 is provided on the upper side of the tower body 11 and connects to the first refrigerant circulation jacket 12, and a first refrigerant inlet 15 is provided on the lower side of the tower body 11 and connects to the first refrigerant circulation jacket 12; the tower body 11 is connected to the atomizing refrigeration tower mounting bracket 70.

[0035] like Figure 4 As shown, the atomizing refrigeration tower 71 also includes a tower bottom 21. A second refrigerant circulation jacket 22 is provided on the inner wall of the tower bottom 21. A second refrigerant outlet 25 is provided at the upper end of the outer wall of the tower bottom 21, and a second refrigerant inlet 24 is provided at the lower end of the outer wall. A tower bottom insulation layer 23 is provided on the outer wall of the tower bottom 21. A discharge port 26 is connected to the bottom of the tower bottom 21. A tower bottom positioning post 20 is connected to the bottom surface of the tower bottom 21 for connection with the lifting support 1. A tray placement platform 29 is provided on the inner wall of the tower bottom 21 for placing material trays 74. A tray removal clearance hole 27 is provided on the tray placement platform 29 to facilitate the removal of the placed material trays 74. The upper end of the tower bottom 21 is a sealing surface 28 for sealing connection with the lower end of the tower body 11. The tower bottom 21 and the lower end of the tower body 11 are connected by a tower body-to-tower bottom connector 34.

[0036] like Figure 5 , 6 As shown, the atomizing freezing tower 71 also includes a tower cover 31, which is connected to the upper end of the tower body 11 via a tower cover-tower body connector 32. A nozzle mounting port 37 is provided on the tower cover 31, and the nozzle mounting port 37 is connected to the atomizing nozzle assembly 72. The atomizing nozzle assembly 72 includes a nozzle connecting fixture 80, on which multiple atomizing nozzles 81 are connected, each atomizing nozzle 81 being connected to a power supply 82. The lower end of the nozzle connecting fixture 80 is connected to the nozzle mounting port 37 via a spray assembly connecting connector 83.

[0037] like Figure 7 As shown, the positioning fixture 77 includes a fixing block 41, which is fixedly connected to the support platform 75. The fixing block 41 is provided with a through bolt 43, and the other end of the bolt 43 is rotatably connected to the countersunk hole 44 opened in the limiting hole 42; the limiting hole 42 abuts against the bottom of the tower 21.

[0038] like Figure 8 As shown, the second refrigerant inlet 24 at the bottom of the tower 21 is connected to the first pipeline 50. The first pipeline 50 is sequentially connected to an inlet temperature probe 51, a control valve 52, a first oil drain valve 53, and a bottom inlet valve 54. The second refrigerant outlet 25 is connected to the first refrigerant inlet 15 of the tower body 11 via a second pipeline 57. The second pipeline 57 is respectively equipped with a bottom outlet valve 56 and a tower body inlet valve 58. The first refrigerant outlet 16 is connected to a third pipeline 61. The third pipeline 61 is sequentially connected to a tower body outlet valve 60, a second oil drain valve 62, and an outlet temperature probe 65. The other end of the outlet temperature probe 65 is connected to a fourth pipeline 66, and the other end of the fourth pipeline 66 is connected to a refrigeration unit 78. The end of the first pipeline 50 facing away from the bottom of the tower 21 is connected to the refrigeration unit 78. A tower temperature probe 63 is also included, used to detect the temperature of the tower body 11, the tower cover 31, and the bottom of the tower 21.

[0039] Install the micro-mesh atomizing nozzle (atomizing nozzle 81) on the top of the tower, place the material tray 74 on the bottom 21 of the atomizing freezing tower, push the moving feed / discharge assembly 76 to press against the positioning fixture 77, and use the drive assembly 5 to initially connect the bottom 21 of the tower to the tower body 11, then use clamps to lock the bottom 21 of the tower to the tower body 11; start the equipment and wait for the temperature of the atomizing freezing tower 71 to reach the temperature set by the operator, then mix the drug with excipients, surfactants, and other excipients to prepare a uniform solution, suspension, or emulsion. Commonly used solvents include water, organic solvents, or mixtures thereof. During preparation, pH and osmotic pressure need to be controlled to ensure drug stability and bioavailability. The prepared drug solution is poured into the storage tank of the atomizing nozzle 81, and the power supply 82 is turned on to atomize the drug solution into the low-temperature freezing tower. After the drug solution is completely atomized, the clamp is loosened, and the drive component 5 is used to separate the tower bottom 21 from the tower body 11. The handle 6 of the moving feed and discharge component 76 is pulled, and the gripper is used to pick up the material tray 74. The material is then transferred to the freeze dryer for sublimation drying to prepare freeze-dried granules in a low-temperature environment. In addition to preparing frozen granules with a particle size of less than 5 micrometers, this equipment can also prepare frozen granules with a particle size of 5 micrometers to 50 micrometers.

[0040] The lifting bracket 1 moves up and down under the action of the drive mechanism 5. The drive mechanism can be a manual adjustment mechanism, a pneumatic adjustment mechanism, or an electric adjustment mechanism. The movable base 2 is connected to the slider, and the operator can slide along the linear slide rail by pulling the handle 6. The lifting bracket reinforcing rib 3 and the lifting bracket reinforcing plate 5 are both to improve the strength of the bracket and prevent deformation. The lifting bracket pad 7 is made of PTFE and is installed between the two brackets to prevent deformation of the simple adjustment component installation area during movement. Due to the smooth surface of the material, this pad can both inhibit deformation and not affect the up and down sliding.

[0041] The tower body 11 is the main site for liquid atomization and freezing. Due to their small particle size, the aerosol particles after atomization and freezing have extremely low flowability. If a conventional conical barrel wall is used for discharge, the frozen aerosol particles will adhere to the conical surface. Even if a vibration method is used for discharge, the material collection rate is less than half. Therefore, the inner wall of the tower adopts a straight barrel shape to improve the material collection rate. The circulating coolant in the first coolant circulation jacket 12 continuously provides cooling to the tower to form a low-temperature environment. In addition to the low-temperature requirement, in order to ensure that the atomized aerosol particles can be completely frozen before falling to the bottom, an annular guide plate 13 is added to make the coolant circulate along the path of the guide plate, so as to fully make the heat transfer of the inner wall of the tower uniform and thus improve the temperature uniformity of the tower. The heat insulation layer 14 of the tower body can reduce the loss of cold energy due to heat exchange with the outside by filling with heat insulation material or by vacuuming.

[0042] The tower bottom positioning column 20 is connected to the atomizing freezing tower positioning hole 8 of the moving feed and discharge assembly. The bottom of the tower bottom 21 is designed with a slope, and the inclination angle is greater than 2° to facilitate the discharge of cleaning water through the discharge port 26 after the tower is cleaned. The sealing surface 28 at the top of the tower bottom needs to be sealed to improve the sealing performance after the tower bottom 21 is connected to the tower body 11. The refrigerant circulating in the second tower bottom refrigerant circulation jacket 22 exchanges heat with the air in the tower bottom 21 to create a low temperature environment for the tower bottom. The tower bottom insulation layer 23 can reduce the loss of cold energy due to heat exchange with the outside by filling with insulation material or by vacuuming. The material tray 74 is placed on the tray placement platform 29. This platform is at a certain height from the upper surface of the tower bottom to avoid affecting the sealing performance of the tray when the tower bottom 21 is assembled with the tower body 11. After the material tray 74 has collected the material, the clamp is used to place the clamp at the tray removal clearance hole 27 and then the tray can be clamped.

[0043] The outer perimeter of the tower cover 31 and the tower body 11 are both tower cover and tower body connectors 32. The top of the tower cover 31 is equipped with several connectors, and the outer perimeter of the bottom of the tower body 11 and the tower base 21 are both tower body and tower base connectors 34. The components can be connected using sanitary clamps. The connection method of the atomizing freezing tower is not limited to clamps; it can be a flange connection or a snap-fit ​​connection.

[0044] The nozzle connecting fixture 80 is connected to the nozzle mounting port 37 in the top of the tower cover 31. The nozzle connecting fixture 80 is divided into several nozzle mounting holes. After the atomizing nozzle 81 is inserted into the nozzle mounting hole, the nozzle position is adjusted and the liquid is added into the liquid storage tank of the nozzle 81. The liquid in the liquid storage tank of the nozzle is pumped through a vibrating micromesh with fine mesh. The micromesh vibrates at a high frequency under the drive of piezoelectric ceramic, so that the liquid is broken into fine droplets when passing through the mesh. The atomized droplets are discharged through the nozzle to form a uniform atomization effect.

[0045] The fixing block 41 is installed on the support platform 75 and connected to the limiting block 42 by bolts 43. The middle bolt serves as a moving rod, and the other two bolts serve as limiting moving rods. After the operator pushes the moving discharge assembly 76 to connect the tower bottom 21 to the tower body 11, the operator rotates the middle bolt 43 to press against the countersunk hole 44 of the limiting block 42, allowing the limiting block 42 to move and press against the moving discharge assembly 76. Then, the other two bolts are tightened to achieve positioning. Subsequently, it is only necessary to press against the positioning fixture 77 to directly assemble the tower bottom 21 and the tower body 11.

[0046] The refrigerant in the refrigeration unit 78 circulates from the first pipeline 50 through the control valve 52 and the bottom inlet valve 54 into the interlayer of the bottom 21 of the tower. Then, it flows from the bottom outlet valve 56 through the second pipeline 57 and the tower body inlet valve 58 into the interlayer of the tower body 11. The refrigerant then flows along the guide plate from the tower body outlet valve 60 into the third pipeline 61, and finally flows along the fourth pipeline 66 into the magnetic pump to complete the refrigerant circulation process in the physicochemical refrigeration tower. The inlet temperature probe 51 and the outlet temperature probe 65 are used to record the temperature of the refrigerant inlet and outlet in real time. Combined with the tower temperature probe 63, it is used to determine whether the ambient temperature inside the tower has reached the temperature value required by the operator. The tower temperature probe 63 consists of three probes that detect the temperature values ​​of the upper part, middle part, and lower part of the tower respectively. The first drain valve 53 and the second drain valve 62 are for the convenience of the operator to discharge the refrigerant when dismantling, transferring, or replacing the refrigerant.

[0047] The operating method of the experimental atomizing freezing device includes the following steps:

[0048] Step 1: Install the atomizing nozzle 81 on the top of the tower, place the material tray 74 on the bottom 21 of the atomizing freezing tower, push the moving feed and discharge assembly 76 to press against the positioning fixture 77, use the drive mechanism 5 to initially connect the bottom 21 of the tower to the tower body 11, and then use clamps to lock the bottom 21 of the tower to the tower body 11.

[0049] Step 2: The circulating refrigerant is introduced from the first pipeline 50 through the control valve 52 and the bottom inlet valve 54 into the second refrigerant circulation jacket 22 of the bottom 21 of the tower through the refrigeration unit 78. Then, it enters the first refrigerant circulation jacket 12 of the tower body 11 through the second pipeline 57 and the tower body inlet valve 58 from the bottom outlet valve 56. The refrigerant enters the third pipeline 61 from the tower body outlet valve 60 along the annular guide plate 13. Finally, it flows into the magnetic pump along the fourth pipeline 66 to complete the refrigerant circulation process in the physicochemical refrigeration tower, so that the tower body 11 reaches a suitable freezing temperature.

[0050] Step 3: Mix the drug with excipients and surfactants to prepare a uniform solution. Pour the prepared solution into the storage tank of the atomizing nozzle 81. Turn on the power supply 82 and the nozzle will atomize the solution into the low-temperature freezing tower. After the solution is completely atomized, loosen the clamps and use the drive mechanism 5 to separate the tower bottom 21 from the tower body 11. Pull the handle 6 of the moving feed and discharge assembly 76 and use the grippers to pick up the material tray 74. Transfer the material to the freeze dryer in a low-temperature environment for sublimation drying to prepare freeze-dried granules.

[0051] This experimental atomizing and freezing device and its operation method involves rapidly freezing droplets atomized by a micro-mesh atomizing nozzle, collecting atomized frozen particles with a diameter of less than 5 μm without melting them, and then transferring the frozen particles to a freeze dryer for freeze-drying to obtain inhalable freeze-dried particles. The non-vacuum characteristics meet the requirements of most experiments, reducing experimental difficulty and cost. The equipment is simple to operate, and the height of the atomizing freeze-drying tower can be increased according to drug or experimental needs. The atomizing function of the micro-mesh atomizing nozzle is not affected during equipment operation. In actual operation, the internal temperature of the tower is below -40℃, and the material collection rate of the bottom tray is high. The particle size detection results after freeze-drying are expected to be below 5 μm, suitable for inhalation. The spray freeze-drying process directly atomizes the drug solution into fine droplets, rapidly freezes them at extremely low temperatures, and then freeze-dries them, preparing porous microspheres of suitable particle size in one step. Compared with pulverization after freeze-drying, spray freeze-drying can better control the size, morphology, and density of particles, reducing losses during pulverization and improving the consistency of formulation performance.

[0052] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An experimental atomizing freezing device, characterized in that, It includes an atomizing freezing tower mounting bracket (70), an atomizing freezing tower (71), a balance cylinder assembly (73), a support platform (75), a moving feed and discharge assembly (76), a positioning fixture (77), and a refrigeration unit (78). The supporting platform (75) is connected to the atomizing freezing tower mounting bracket (70), and the atomizing freezing tower (71) is connected to the atomizing freezing tower mounting bracket (70); the supporting platform (75) is also connected to a moving feed and discharge assembly (76) and a positioning fixture (77), the moving feed and discharge assembly (76) is used for material transfer, and the positioning fixture (77) is used for positioning the atomizing freezing tower (71); the refrigeration unit (78) is set on one side of the supporting platform (75) and connected to the atomizing freezing tower (71); the balance cylinder assembly (73) is connected to the atomizing freezing tower mounting bracket (70) and connected to the pipe connecting the refrigeration unit (78) and the atomizing freezing tower (71); The atomizing freezing tower (71) includes a tower body (11), the inner wall of which is provided with a first refrigerant circulation jacket (12), and an annular guide plate (13) is provided between the first refrigerant circulation jacket (12) and the tower body (11). A tower body insulation layer (14) is provided on the outer side of the tower body (11). A first refrigerant outlet (16) is provided on the upper side of the tower body (11) and connects to the first refrigerant circulation jacket (12). A first refrigerant inlet (15) is provided on the lower side of the tower body (11) and connects to the first refrigerant circulation jacket (12). The tower body (11) is connected to the atomizing freezing tower mounting bracket (70). The atomizing freezing tower (71) also includes a tower cover (31), on which a nozzle mounting port (37) is provided, and the nozzle mounting port (37) is connected to the atomizing nozzle assembly (72). The atomizing nozzle assembly (72) includes a nozzle connecting fixture (80), on which multiple atomizing nozzles (81) are connected, and the atomizing nozzles (81) are micro-mesh atomizing nozzles.

2. The experimental atomizing freezing device according to claim 1, characterized in that, The mobile feeding and discharging assembly (76) includes a mobile base (2), on which a slider mounting hole (9) is provided for sliding connection with the support platform (75); a drive mechanism (5) is connected to the mobile base (2), and the drive mechanism (5) is connected to a lifting bracket (1). A lifting bracket reinforcing rib (3) is provided on the front side of the lifting bracket (1), and a lifting bracket reinforcing plate (4) is provided on the rear side. A positioning hole (8) for the bottom of the atomizing freezing tower is provided on the lifting bracket (1); a lifting bracket pad (7) is provided between the drive mechanism (5) and the lifting bracket (1); and a handle (6) is provided on the rear side of the drive mechanism (5).

3. The experimental atomizing freezing device according to claim 2, characterized in that, The atomizing refrigeration tower (71) also includes a tower bottom (21), the inner wall of which is provided with a second refrigerant circulation jacket (22), the upper end of the outer wall of the tower bottom (21) is provided with a second refrigerant outlet (25), and the lower end of the outer wall is provided with a second refrigerant inlet (24); the outer wall of the tower bottom (21) is provided with a tower bottom insulation layer (23); the bottom of the tower bottom (21) is connected to a discharge port (26); the bottom surface of the tower bottom (21) is connected to a tower bottom positioning column (20) for connecting with the lifting bracket (1); the inner wall of the tower bottom (21) is provided with a tray placement platform (29) for placing a material tray (74); the tray placement platform (29) is provided with a tray removal clearance hole (27) to facilitate the removal of the material tray (74); the upper end of the tower bottom (21) is a sealing surface (28) for sealing connection with the lower end of the tower body (11).

4. The experimental atomizing freezing device according to claim 3, characterized in that, The tower cover (31) is connected to the upper end of the tower body (11) via a tower cover-tower body connector (32).

5. The experimental atomizing freezing device according to claim 4, characterized in that, Each of the atomizing nozzles (81) is connected to a power source (82); the lower end of the nozzle connecting fixture (80) is connected to the nozzle mounting port (37) via a spray assembly connecting connector (83).

6. The experimental atomizing freezing device according to claim 3, characterized in that, The positioning fixture (77) includes a fixing block (41), which is fixedly connected to the support platform (75). The fixing block (41) is provided with a through bolt (43), and the other end of the bolt (43) is rotatably connected to the countersunk hole (44) opened in the limiting hole (42); the limiting hole (42) abuts against the bottom of the tower (21).

7. The experimental atomizing freezing device according to claim 4, characterized in that, The second refrigerant inlet (24) at the bottom of the tower (21) is connected to the first pipeline (50), and the first pipeline (50) is connected in sequence to the inlet temperature probe (51), the control valve (52), the first oil drain valve (53) and the bottom inlet valve (54); the second refrigerant outlet (25) is connected to the first refrigerant inlet (15) of the tower body (11) through the second pipeline (57), and the second pipeline (57) is respectively provided with the bottom outlet valve (56) and the tower body inlet valve (58); the first refrigerant outlet (16) is connected to the third pipeline (61), and the third pipeline (61) is connected in sequence to the tower body outlet valve (60), the second oil drain valve (62) and the outlet temperature probe (65), the other end of the outlet temperature probe (65) is connected to the fourth pipeline (66), the other end of the fourth pipeline (66) is connected to the refrigeration unit (78), and the end of the first pipeline (50) away from the bottom of the tower (21) is connected to the refrigeration unit (78).

8. The experimental atomizing freezing device according to claim 7, characterized in that, It also includes a tower temperature probe (63) for detecting the temperature of the tower body (11), the tower cover (31) and the tower bottom (21).

9. The experimental atomizing freezing device according to claim 3, characterized in that, The bottom of the tower (21) is connected to the lower end of the tower body (11) through a tower body-tower bottom connector (34).

10. The operating method of the experimental atomizing freezing device as described in claim 1, characterized in that, Includes the following steps: Step 1: Install the atomizing nozzle (81) on the top of the tower, place the material tray (74) on the bottom (21) of the atomizing freezing tower, push the moving feed and discharge assembly (76) against the positioning fixture (77), and use the drive mechanism (5) to initially connect the bottom (21) of the tower to the tower body (11), and then use clamps to lock the bottom (21) of the tower to the tower body (11). Step 2: The circulating refrigerant is introduced from the first pipeline (50) through the control valve (52) and the bottom inlet valve (54) into the second refrigerant circulation jacket (22) at the bottom of the tower (21) via the refrigeration unit (78). Then, it enters the first refrigerant circulation jacket (12) in the tower body (11) through the second pipeline (57) and the tower body inlet valve (58) via the bottom outlet valve (56). The refrigerant enters the third pipeline (61) from the tower body outlet valve (60) along the annular guide plate (13). Finally, it flows into the magnetic pump along the fourth pipeline (66) to complete the refrigerant circulation process in the physicochemical refrigeration tower, so that the tower body (11) reaches a suitable freezing temperature. Step 3: Mix the drug with excipients and surfactants to prepare a uniform solution. Pour the prepared drug solution into the storage tank of the atomizing nozzle (81). Turn on the power (82) and the nozzle will atomize the drug solution into the low-temperature freezing tower. After the drug solution is completely atomized, loosen the clamps and use the drive mechanism (5) to separate the bottom (21) of the tower from the tower body (11). Pull the handle (6) of the moving feed and discharge assembly (76) and then use the grippers to pick up the material tray (74) and transfer it to the freeze dryer for sublimation drying to prepare freeze-dried granules in a low-temperature environment.

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