CN220366615U - Spray freeze drying system for determining spray freeze drying endpoint - Google Patents
Spray freeze drying system for determining spray freeze drying endpoint Download PDFInfo
- Publication number
- CN220366615U CN220366615U CN202322999659.XU CN202322999659U CN220366615U CN 220366615 U CN220366615 U CN 220366615U CN 202322999659 U CN202322999659 U CN 202322999659U CN 220366615 U CN220366615 U CN 220366615U
- Authority
- CN
- China
- Prior art keywords
- freeze drying
- temperature
- spray
- pressure
- determining
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000004108 freeze drying Methods 0.000 title claims abstract description 130
- 239000007921 spray Substances 0.000 title claims abstract description 97
- 238000001514 detection method Methods 0.000 claims abstract description 73
- 239000000463 material Substances 0.000 claims abstract description 40
- 230000000149 penetrating effect Effects 0.000 claims description 3
- 238000005516 engineering process Methods 0.000 abstract description 4
- 238000001035 drying Methods 0.000 description 64
- 238000000034 method Methods 0.000 description 21
- 238000000859 sublimation Methods 0.000 description 13
- 230000008022 sublimation Effects 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000005265 energy consumption Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108091005461 Nucleic proteins Proteins 0.000 description 3
- 108010078233 Thymalfasin Proteins 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 3
- 229960004231 thymalfasin Drugs 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000004836 empirical method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004134 energy conservation Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
Landscapes
- Drying Of Solid Materials (AREA)
Abstract
The utility model provides a spray freeze drying system for determining a spray freeze drying endpoint. A spray freeze drying system for determining a spray freeze drying endpoint comprising: a spray freeze dryer comprising a support member for receiving frozen material; the cold trap device is provided with an air inlet and an air outlet, and the air inlet is communicated with an air outlet of the freeze drying cavity; the temperature detection module is used for detecting the temperature of the bearing member and the temperature of the material; the pressure detection module is used for detecting the pressure of the exhaust port and the pressure of the air outlet; and the control device is respectively in control connection with the temperature detection module and the pressure detection module so as to determine the spray freeze drying end point according to the temperature difference between the bearing member and the material and the pressure difference between the exhaust port and the air outlet. The technical scheme of the utility model solves the problems of small application range, low judging precision and higher equipment cost of the spray freeze drying end point judging technology in the prior art.
Description
Technical Field
The utility model relates to the technical field of spray freeze drying, in particular to a spray freeze drying system for judging a spray freeze drying end point.
Background
At present, for the biological medicine industry, the biological pharmacy of polypeptide, protein and nucleic acid is increasingly used for treating different diseases, has the advantages of high bioavailability, strong targeting property and the like, and has special curative effects on hereditary/non-hereditary diseases such as tumor, cancer, pneumonia, hepatitis B and the like. However, these drugs are also mostly expensive and are usually solid powders for low temperature storage and transportation. The biosolid powder with high added value is generally prepared into a finished product by adopting a spray freeze drying technology, so that the product with a porous structure, which has good sphericity, narrow particle size distribution range, high specific surface area, good stability and good rehydration, can be obtained, and can also keep high bioactivity and bioavailability of the product. The spray freeze drying technology has the defects of high energy consumption, the energy consumption ratio of the drying stage is about 80-90%, the drying stage is divided into a sublimation drying stage and a resolution drying stage, the accurate judgment of the drying end points of the two stages can reduce ineffective drying, and the drying efficiency is improved, wherein the judgment of the sublimation drying end points has great influence on the whole freeze drying process, and the method is also a research hot spot.
The method for judging the drying end point is mainly divided into a theoretical model method and a test method, wherein the theoretical model method lacks heat and humidity migration characteristic data related to transfer resistance, external mass transfer coefficient, dry layer steam diffusion coefficient, product characteristics and the like, and the understanding of the mechanism of heat and mass transfer in freeze drying is not deep and unclear, so that the models are limited in a narrow range of freeze drying conditions. Thus, for spray freeze drying equipment, the materials and lyophilization conditions selected are not constant, and the drying endpoint determination is preferably performed experimentally. The judgment of the sublimation drying end point is particularly important, if the end point of the sublimation drying stage is judged prematurely, partial free water of the preparation is not completely dried, the temperature is increased to enter the analysis drying stage, the product is disintegrated or melted, and the product quality is unpredictably influenced. If too late a judgment would be energy consuming and time consuming, which is contrary to the production concept.
In the prior art, the test method mainly comprises a weighing method, a moisture absorption rate method, a pressure rising method, a residual gas analyzer, pulse nuclear magnetic resonance and other methods. The weighing method judges whether the drying is finished or not by directly measuring the mass of the material, but the method is only suitable for single material, is not suitable for mass industrial production and depends on the design of a freeze dryer. The method for determining the drying degree of the product with different drying time lengths according to the formula for calculating the moisture absorption rate is intermittent, and a large number of experiments are needed for determining the drying of one product, so that the operation is complicated and the application range is small. The pressure rising method is to close the butterfly valve before drying, if the rising of the pressure indicates that the drying is not finished, the method is finished. However, the method is very dependent on the leakage rate of the drying chamber and is constant, the correct drying end point prompt can be given only by the relative change rate of pressure rise, but because various sealing gaskets are leaked due to steam sterilization and the like, the leakage rate is often an uncertain value, so that the spray freeze drying end point is easy to have errors and the problem of low judgment precision is easy to occur. The residual gas analyzer, although being applicable to drying end point judgment, has the disadvantages of very high cost, overlarge equipment volume and the like, which limit the application of the residual gas analyzer. Pulsed nuclear magnetic resonance is generally used to determine the state of moisture in food products and is costly to equipment. Therefore, the above method for determining the spray freeze drying end point is prone to problems of small application range, low determination accuracy and high equipment cost.
Disclosure of Invention
The utility model mainly aims to provide a spray freeze drying system for judging a spray freeze drying end point, so as to solve the problems of small application range, low judging precision and higher equipment cost of a spray freeze drying end point judging technology in the prior art.
In order to achieve the above object, the present utility model provides a spray freeze drying system for judging a spray freeze drying end point, comprising: a spray freeze dryer comprising a housing defining a freeze drying chamber and a support member disposed within the freeze drying chamber for receiving frozen material; the cold trap device is positioned at one side of the spray freeze dryer and is provided with an air inlet and an air outlet, and the air inlet is communicated with an air outlet of the freeze drying cavity; the temperature detection module is arranged on the spray freeze dryer and is used for detecting the temperature of the bearing member and the temperature of the material; the pressure detection module is used for detecting the pressure of the exhaust port and the pressure of the air outlet; and the control device is respectively in control connection with the temperature detection module and the pressure detection module so as to determine the spray freeze drying end point according to the temperature difference between the bearing member and the material and the pressure difference between the exhaust port and the air outlet.
Further, the spray freeze drying system for determining a spray freeze drying endpoint further comprises: one end of the vacuumizing pipeline is directly connected with the exhaust port, and the other end of the vacuumizing pipeline is directly connected with the air inlet; the humidity detection component is arranged on the vacuumizing pipeline and used for detecting the air humidity in the vacuumizing pipeline and is in control connection with the control device.
Further, the pressure detection module includes: the first pressure detection piece is positioned between the humidity detection component and the exhaust port and is used for detecting the pressure in the vacuumizing pipeline; the second pressure detection piece is arranged at the air outlet to detect the pressure intensity at the air outlet.
Further, the spray freeze drying system for determining a spray freeze drying endpoint further comprises: the third pressure detection piece is arranged on the shell and is in control connection with the control device, and at least part of the third pressure detection piece is positioned in the freeze drying cavity; the control valve is arranged on the vacuumizing pipeline, is positioned between the humidity detection component and the air outlet, and is used for controlling the connection or disconnection of the air outlet and the air inlet.
Further, the temperature detection module includes: a first temperature detecting piece, at least part of which is contacted with the bottom of the supporting member so as to detect the temperature of the supporting member; and the second temperature detection piece is positioned above the bearing member so as to detect the temperature of the material on the bearing member.
Further, the second temperature detecting piece comprises a temperature detecting main body arranged outside the shell and a temperature detecting end connected with the temperature detecting main body, wherein the temperature detecting end is positioned in the freeze drying cavity, and the temperature detecting end penetrates through and extends out of the supporting member from bottom to top.
Further, the support member includes: the support piece is connected to the inner wall of the shell; and the tray is detachably connected with the supporting piece, and the first temperature detection piece is used for detecting the temperature of the tray.
Further, the spray freeze drying system for judging the spray freeze drying end point further comprises a vacuumizing pump and a connecting pipeline for connecting the air outlet and the vacuumizing pump, and the second pressure detecting piece is arranged on the connecting pipeline.
Further, the spray freeze drying system for judging the spray freeze drying end point further comprises a third temperature detection piece arranged on the shell, and at least part of the third temperature detection piece stretches into the freeze drying cavity.
Further, the control device includes: the receiving module is connected with the temperature detection module and the pressure detection module to receive the data acquired by the temperature detection module and the pressure detection module; the calculating module is connected with the receiving module and is used for calculating the temperature difference between the bearing member and the material and the pressure difference between the exhaust port and the air outlet; the judging module is connected with the calculating module and is used for judging whether the temperature difference is smaller than a temperature preset value in a first preset time and judging whether the pressure difference is smaller than a pressure preset value in a second preset time.
By applying the technical scheme of the utility model, the temperature detection module is arranged on the spray freeze dryer and used for detecting the temperature of the supporting member and the temperature of the material, and the pressure detection module detects the pressure of the exhaust port and the pressure of the air outlet, so that on one hand, on-line real-time monitoring, control and recording can be performed, a large number of repeated parallel experiments are avoided, and the spray freeze dryer is suitable for spray freeze drying of high-added-value medicines of most polypeptides, nucleic acids and proteins, so that the application range is increased and the operation is simple; on the other hand, the freeze-drying end point can be determined according to the cooperation of the temperature and the pressure, so that the accuracy and the correctness of the judgment of the drying end point can be ensured multiple times, the material can be ensured to be transferred from the sublimation drying stage to the analysis drying stage in time, the continuous energy consumption and time consumption are avoided, and partial product disintegration caused by the fact that the material enters the analysis drying stage in advance can be avoided; in still another aspect, the temperature detection module and the pressure detection module have lower cost than those of the residual gas analyzer and the pulse nuclear magnetic resonance in the prior art, so the spray freeze drying system for determining the spray freeze drying endpoint of the embodiment can solve the problems of small application range, low determination precision and higher equipment cost.
Drawings
The accompanying drawings, which are included to provide a further understanding of the utility model and are incorporated in and constitute a part of this specification, illustrate embodiments of the utility model and together with the description serve to explain the utility model. In the drawings:
FIG. 1 shows a schematic diagram of an embodiment of a spray-freeze drying system of the present utility model for determining a spray-freeze drying endpoint;
fig. 2 shows a particle size distribution diagram of thymalfasin after lyophilization using the spray freeze drying system of fig. 1 for determining the spray freeze drying endpoint.
Wherein the above figures include the following reference numerals:
11. a housing; 12. a support member; 121. a support; 122. a tray; 13. a vacuum pump; 15. a connecting pipeline; 21. a cold trap device; 22. a vacuumizing pipeline; 23. a humidity detection member; 30. a temperature detection module; 31. a first temperature detecting member; 32. a second temperature detecting member; 33. a third temperature detecting member; 50. a pressure detection module; 51. a first pressure detecting member; 52. a second pressure detecting member; 53. a third pressure detecting member; 55. and a control valve.
Detailed Description
It should be noted that, in the case of no conflict, the embodiments and features in the embodiments may be combined with each other. The utility model will be described in detail below with reference to the drawings in connection with embodiments.
As shown in fig. 1, an embodiment of the present utility model provides a spray-freeze drying system for determining a spray-freeze drying endpoint. The spray freeze drying system for determining the spray freeze drying endpoint includes a spray freeze dryer, a cold trap device 21, a temperature detection module 30, a pressure detection module 50, and a control device. Wherein the spray freeze dryer comprises a housing 11 defining a freeze drying chamber and a support member 12 disposed within the freeze drying chamber for receiving frozen material; the cold trap device 21 is positioned at one side of the spray freeze dryer, the cold trap device 21 is provided with an air inlet and an air outlet, and the air inlet is communicated with an air outlet of the freeze drying cavity; the temperature detection module 30 is arranged on the spray freeze dryer, and the temperature detection module 30 is used for detecting the temperature of the supporting member 12 and the temperature of the material; the pressure detection module 50 is used for detecting the pressure of the exhaust port and the pressure of the air outlet; the control device is in control connection with the temperature detection module 30 and the pressure detection module 50 respectively to determine the spray freeze drying end point according to the temperature difference between the bearing member 12 and the material and the pressure difference between the air outlet and the air outlet.
In the above technical solution, the temperature detection module 30 is disposed in the spray freeze dryer and is used for detecting the temperature of the supporting member 12 and the temperature of the material, and the pressure detection module 50 detects the pressure of the air outlet and the pressure of the air outlet, so on one hand, on-line real-time monitoring, control and recording can be performed, a large number of repeated parallel experiments are avoided, and the spray freeze drying device is suitable for spray freeze drying of high-added value medicines of most polypeptides, nucleic acids and proteins, so that the application range is increased and the operation is simple; on the other hand, the freeze-drying end point can be determined according to the cooperation of the temperature and the pressure, so that the accuracy and the correctness of the judgment of the drying end point can be ensured multiple times, the material can be ensured to be transferred from the sublimation drying stage to the analysis drying stage in time, the continuous energy consumption and time consumption are avoided, and partial product disintegration caused by the fact that the material enters the analysis drying stage in advance can be avoided; in yet another aspect, the temperature detection module 30 and the pressure detection module 50 have lower cost than the residual gas analyzer and the pulse nuclear magnetic resonance in the prior art, and therefore, the spray freeze drying system for determining the spray freeze drying endpoint of the present embodiment can solve the problems of small application range, low determination accuracy and higher equipment cost.
In the embodiment of the present utility model, the control and recording may be performed by a control device or may be performed manually.
The spray freeze drying system for determining a spray freeze drying end point according to the embodiment of the present utility model is particularly suitable for determining a sublimation drying end point and also suitable for determining an analytical drying end point.
It should be noted that, the embodiment of the utility model adopts the test method to determine the drying end point, is not limited to the specific drying condition or the theoretical model method suitable for the dried product, has universality, is not limited to the pharmaceutical industry, and is still suitable for the food industry.
In the embodiment of the present utility model, the pressure difference=the pressure value of the exhaust port-the pressure value of the air outlet, that is, the pressure difference=the pressure value of the air inlet of the cold-trap device 21-the pressure value of the air outlet of the cold-trap device 21, that is, the pressure difference is the pressure difference between the front and rear of the cold-trap device 21.
Preferably, in the embodiment of the present utility model, the control device is a PLC control cabinet, which can be connected with all the sensors described below in a control manner, and continuously record relevant data in real time on line.
It should be noted that, the spray freeze dryer according to the embodiment of the present utility model is used for freeze drying materials, the cold trap device is used for removing water vapor in the gas discharged from the gas outlet, the specific structure is available in the prior art, and is not described herein, and the spray freeze dryer and the cold trap device are both connected to a refrigerator.
Specifically, in an embodiment of the present utility model, the control device includes a receiving module, a calculating module, and a judging module. The receiving module is connected with the temperature detecting module 30 and the pressure detecting module 50 to receive data collected by the temperature detecting module 30 and the pressure detecting module 50; the calculating module is connected with the receiving module and is used for calculating the temperature difference between the bearing member 12 and the materials and the pressure difference between the exhaust port and the air outlet; the judging module is connected with the calculating module and is used for judging whether the temperature difference is smaller than a temperature preset value in a first preset time and judging whether the pressure difference is smaller than a pressure preset value in a second preset time. Thus, if the temperature difference is less than the temperature preset value within the first preset time and the pressure difference is less than the pressure preset value within the second preset time, the spray freeze drying end point can be determined. The temperature preset value, the first preset time, the pressure preset value and the second preset time are all empirical values.
In one embodiment, the control device may not be provided with a judging module, and the technician may also compare the temperature difference with a preset temperature value and compare the pressure difference with the preset pressure value to determine the spray freeze drying end point.
As shown in fig. 1, in the embodiment of the present utility model, the spray freeze drying system for determining the end point of spray freeze drying further includes a vacuum line 22 and a humidity detection member 23. One end of the vacuumizing pipeline 22 is directly connected with the air outlet, and the other end of the vacuumizing pipeline 22 is directly connected with the air inlet; the humidity detecting member 23 is disposed in the vacuumizing tube 22 and is used for detecting the air humidity in the vacuumizing tube 22, and the humidity detecting member 23 is in control connection with the control device.
Through the arrangement, the humidity condition can be increased, so that the spray freeze drying end point can be judged cooperatively through the temperature, the pressure and the humidity, and the accuracy and the correctness of judging the spray freeze drying end point are improved.
Preferably, in the embodiment of the present utility model, the humidity detecting member 23 is a humidity sensor.
As shown in fig. 1, in the embodiment of the present utility model, the pressure detecting module 50 includes a first pressure detecting member 51 and a second pressure detecting member 52. Wherein, the first pressure detecting piece 51 is located between the humidity detecting member 23 and the air outlet, and the first pressure detecting piece 51 is used for detecting the pressure in the vacuumizing pipeline 22; the second pressure detecting member 52 is provided at the air outlet to detect the pressure at the air outlet.
Through the arrangement, the pressure intensity of the air outlet and the pressure intensity of the air outlet can be detected, so that the pressure difference between the air outlet and the air outlet can be obtained.
The first pressure detecting member 51 detects that the fluid, i.e., the gas, before passing through the cold trap device 21 contains water vapor, and the second pressure detecting member 52 detects that the fluid, i.e., the gas, after passing through the cold trap device 21 removes water vapor.
Preferably, in the embodiment of the present utility model, the first pressure detecting member 51 and the second pressure detecting member 52 are pressure sensors, and the pressure sensors can detect the pressure of the liquid and the gas.
As shown in fig. 1, in the embodiment of the present utility model, the spray freeze drying system for determining the end point of spray freeze drying further includes a third pressure detecting element 53 and a control valve 55. The third pressure detecting piece 53 is arranged in the shell 11, the third pressure detecting piece 53 is in control connection with the control device, and at least part of the third pressure detecting piece 53 is positioned in the freeze drying cavity; the control valve 55 is disposed on the vacuumizing line 22, the control valve 55 is disposed between the humidity detecting member 23 and the air outlet, and the control valve 55 is used for controlling the communication or disconnection between the air outlet and the air inlet.
By controlling the control valve 55 to disconnect the exhaust port from the intake port in the above-described arrangement, by observing whether the value of the third pressure detecting member 53 rises within 10 minutes, if not, that is, if the pressure rise is less than or equal to 0.67Pa/h, the drying end point can be confirmed, and thus, the condition for determining the drying end point can be increased, thereby making the drying end point judgment more accurate and precise.
Preferably, in the embodiment of the present utility model, the third pressure detecting member 53 is a pressure sensor.
Preferably, in an embodiment of the present utility model, the control valve 55 is a vacuum valve.
As shown in fig. 1, in the embodiment of the present utility model, the temperature detecting module 30 includes a first temperature detecting member 31 and a second temperature detecting member 32. Wherein at least part of the first temperature detecting piece 31 is in contact with the bottom of the supporting member 12 to detect the temperature of the supporting member 12; at least a portion of the second temperature sensing element 32 is positioned above the support member 12 to sense the temperature of the material on the support member 12.
By the above arrangement, the temperature of the holding member 12 and the temperature of the material can be detected to obtain the temperature difference between the holding member 12 and the material.
Preferably, in the embodiment of the present utility model, the first temperature detecting element 31 and the second temperature detecting element 32 are temperature sensors, wherein the first temperature detecting element 31 is preferably a patch type temperature sensor, and the second temperature detecting element 32 is preferably a PT100 temperature sensor.
As shown in fig. 1, in the embodiment of the present utility model, the second temperature detecting element 32 includes a temperature detecting body disposed outside the housing 11 and a temperature detecting end connected to the temperature detecting body, the temperature detecting end is located in the freeze drying chamber, and the temperature detecting end penetrates through and extends out of the supporting member 12 from bottom to top. Therefore, the temperature detection end can be fully contacted with the material in the vertical direction, and the temperature detection accuracy is improved.
Specifically, in the embodiment of the present utility model, the temperature detection module 30 further includes a temperature sleeve penetrating the support member 12, and the temperature detection end is located in the temperature sleeve.
As shown in fig. 1, in an embodiment of the present utility model, the bearing member 12 includes a support 121 and a tray 122. Wherein the supporting member 121 is connected to the inner wall of the housing 11; the tray 122 is detachably connected to the support 121, and the first temperature detecting member 31 is used for detecting the temperature of the tray 122. Since the cooling function is mainly performed by the tray 122, the first temperature detecting member 31 is used for detecting the temperature of the tray 122, so that the accuracy of temperature detection can be improved.
As shown in fig. 1, in the embodiment of the present utility model, the spray freeze drying system for determining the end point of spray freeze drying further includes a vacuum pump 13 and a connection pipe 15 for connecting the air outlet and the vacuum pump 13, and the second pressure detecting member 52 is disposed on the connection pipe 15. In this way, a vacuum can be drawn on the lyophilization chamber.
As shown in fig. 1, in the embodiment of the present utility model, the spray freeze drying system for determining the end point of spray freeze drying further includes a third temperature detecting element 33 disposed in the housing 11, at least a portion of the third temperature detecting element 33 extending into the freeze drying chamber.
Specifically, in the embodiment of the present utility model, the spray freeze drying system for determining the end point of spray freeze drying further includes a temperature sleeve penetrating the housing 11, and the temperature probe of the third temperature detecting element 33 extends into the temperature sleeve.
The spray freeze drying end point includes a sublimation drying end point and an analytical drying end point, wherein the conditions for judging the sublimation drying end point are as follows:
the difference in temperature value (temperature difference) between the temperature of the first and second support members 12 and the temperature of the material is less than 5 ℃ and needs to be maintained for at least 1h;
the pressure difference between the second air outlet and the air outlet is not more than 5Pa, and the second air outlet and the air outlet need to be maintained for at least 1h;
third, the air humidity in the evacuation line 22 is less than or equal to 3% RH and needs to be maintained for at least 1 hour;
when the above conditions are satisfied, the control valve 55 on the evacuation line 22 may be closed, and it is recorded whether the value of the third pressure detecting element 53 increases within 10 minutes, and if the value does not increase significantly (i.e., the pressure increase is less than or equal to 0.67 Pa/h), it is determined that the drying end point of the first stage (sublimation drying stage) is over, and the analytical drying stage may be entered.
Judging conditions for analyzing the drying end point:
first, when the temperature is raised to the temperature required for resolution drying, the temperature of the material is substantially the same as the temperature of the support member 12 (i.e., the temperature difference between the temperature of the material and the temperature of the support member 12 is less than 3 ℃), and it is necessary to maintain the temperature for at least 1 hour;
the pressure in the second drying oven (the pressure detected by the first pressure detecting member 51) and the pressure detected by the second pressure detecting member 52 (the pressure at the air outlet) tend to be consistent (i.e. the pressure difference between the pressure detected by the first pressure detecting member 51 and the pressure detected by the second pressure detecting member 52 is not more than 5 Pa), and is maintained for at least 1h;
the third, first pressure sensing element 51 is substantially restored to the idle condition of the device and maintained for at least 1 hour. The index of the equipment in idle state refers to the limit pressure value measured by the first pressure detecting member 51 after the freeze drying cavity is empty of materials and vacuumized.
Preferably, in the embodiment of the present utility model, the first pressure detecting member 51 and the second pressure detecting member 52 are both vacuum gauges.
When the above conditions are satisfied, the time of the whole analytical drying stage is not less than 4 hours, and the drying is considered to be finished.
It should be noted that, in the embodiment of the utility model, more economical temperature, humidity and pressure are adopted to monitor the freeze-drying condition together and comprehensively judge the drying end point, when the three conditions reach the set parameter conditions, the drying end points of two stages are determined to be reached, so that the judging accuracy of the drying end point can be improved, and under the condition that the freeze-drying quality and the bioactivity of the product are ensured, the prompt of ending each drying stage can be timely and accurately given, so that the materials are not prevented from entering the analysis heating stage in advance to produce 'bad materials', and the effects of energy conservation and emission reduction can be realized.
It should be noted that the embodiments of the present utility model employ a temperature sensor, a pressure sensor, and a humidity sensor for determining a drying end point, which are relatively economical and have a small and well-installed detection apparatus and can be adapted to a freeze-drying environment.
100g of thymalfasin aqueous solution was spray-freeze-dried using the spray-freeze-drying system for determining the spray-freeze-drying endpoint of this example: after the process of batching, precooling, spraying, freezing, sublimation drying and analytical drying is carried out, after the condition of sublimation drying is met after 15 hours, the process is kept for 1 hour, then the process enters an analytical drying stage, the temperature is gradually increased to 20 ℃ after entering the analytical drying stage, and after the process reaches the end point of analytical drying after 4 hours, the sample is taken out and sent to analysis and characterization.
In addition, according to the sample analysis, the present example can obtain a product having characteristics substantially consistent with those of the product obtained by the empirical method, such as extremely fine powder having Dv (50) =9.22 μm in fig. 2, which has a high sphericity, is porous, has a moisture content of <5%, and is excellent in biological activity and rehydration property of thymalfasin, as compared with the drying time given by the empirical method for at least 48 hours.
From the above description, it can be seen that the above embodiments of the present utility model achieve the following technical effects: the temperature detection module is arranged on the spray freeze dryer and used for detecting the temperature of the bearing member and the temperature of the material, and the pressure detection module detects the pressure of the exhaust port and the pressure of the air outlet, so that on one hand, on-line real-time monitoring, control and recording can be performed, a large number of repeated parallel experiments are avoided, and the spray freeze dryer is suitable for spray freeze drying of high-added value medicines of most polypeptides, nucleic acids and proteins, so that the application range is increased, and the operation is simple; on the other hand, the freeze-drying end point can be determined according to the cooperation of the temperature and the pressure, so that the accuracy and the correctness of the judgment of the drying end point can be ensured multiple times, the material can be ensured to be transferred from the sublimation drying stage to the analysis drying stage in time, the continuous energy consumption and time consumption are avoided, and partial product disintegration caused by the fact that the material enters the analysis drying stage in advance can be avoided; in still another aspect, the temperature detection module and the pressure detection module have lower cost than those of the residual gas analyzer and the pulse nuclear magnetic resonance in the prior art, so the spray freeze drying system for determining the spray freeze drying endpoint of the embodiment can solve the problems of small application range, low determination precision and higher equipment cost.
The above description is only of the preferred embodiments of the present utility model and is not intended to limit the present utility model, but various modifications and variations can be made to the present utility model by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present utility model should be included in the protection scope of the present utility model.
Claims (10)
1. A spray freeze drying system for determining a spray freeze drying endpoint comprising:
spray freeze dryer comprising a housing (11) defining a freeze drying chamber and a support member (12) disposed within the freeze drying chamber for receiving frozen material;
a cold trap device (21) positioned at one side of the spray freeze dryer, wherein the cold trap device (21) is provided with an air inlet and an air outlet, and the air inlet is communicated with an air outlet of the freeze drying cavity;
the temperature detection module (30) is arranged on the spray freeze dryer, and the temperature detection module (30) is used for detecting the temperature of the bearing member (12) and the temperature of the material;
a pressure detection module (50) for detecting the pressure of the exhaust port and the pressure of the air outlet;
and the control device is respectively in control connection with the temperature detection module (30) and the pressure detection module (50) so as to determine a spray freeze drying end point according to the temperature difference between the bearing member (12) and the material and the pressure difference between the exhaust port and the air outlet.
2. The spray freeze drying system for determining a spray freeze drying endpoint according to claim 1, wherein the spray freeze drying system for determining a spray freeze drying endpoint further comprises:
one end of the vacuumizing pipeline (22) is directly connected with the exhaust port, and the other end of the vacuumizing pipeline (22) is directly connected with the air inlet;
the humidity detection component (23) is arranged on the vacuumizing pipeline (22) and used for detecting the air humidity in the vacuumizing pipeline (22), and the humidity detection component (23) is in control connection with the control device.
3. Spray-freeze drying system for determining a spray-freeze drying endpoint according to claim 2, characterized in that the pressure detection module (50) comprises:
a first pressure detecting member (51) located between the humidity detecting member (23) and the exhaust port, the first pressure detecting member (51) being configured to detect a pressure in the evacuation line (22);
and a second pressure detecting member (52) provided at the air outlet to detect the pressure at the air outlet.
4. The spray freeze drying system for determining a spray freeze drying endpoint according to claim 2, wherein the spray freeze drying system for determining a spray freeze drying endpoint further comprises:
the third pressure detection piece (53) is arranged in the shell (11), the third pressure detection piece (53) is in control connection with the control device, and at least part of the third pressure detection piece (53) is positioned in the freeze drying cavity;
the control valve (55) is arranged on the vacuumizing pipeline (22), the control valve (55) is positioned between the humidity detection component (23) and the exhaust port, and the control valve (55) is used for controlling the connection or disconnection of the exhaust port and the air inlet.
5. Spray-freeze drying system for determining a spray-freeze drying endpoint according to any one of claims 1 to 4, characterized in that the temperature detection module (30) comprises:
a first temperature detector (31), at least part of the first temperature detector (31) being in contact with the bottom of the support member (12) to detect the temperature of the support member (12);
and a second temperature detector (32), at least part of the second temperature detector (32) is positioned above the supporting member (12) so as to detect the temperature of the material on the supporting member (12).
6. The spray freeze drying system for determining a spray freeze drying endpoint according to claim 5, wherein the second temperature detecting element (32) comprises a temperature detecting body disposed outside the housing (11) and a temperature detecting end connected to the temperature detecting body, the temperature detecting end being located in the freeze drying chamber from bottom to top, the temperature detecting end penetrating and extending out of the support member (12).
7. Spray-freeze drying system for determining a spray-freeze drying endpoint according to claim 5, characterized in that the support member (12) comprises:
a support (121) connected to the inner wall of the housing (11);
and a tray (122) detachably connected to the support member (121), wherein the first temperature detecting member (31) is configured to detect a temperature of the tray (122).
8. A spray freeze drying system for determining a spray freeze drying endpoint according to claim 3, further comprising a vacuum pump (13) and a connecting line (15) for connecting the air outlet and the vacuum pump (13), the second pressure detecting member (52) being provided in the connecting line (15).
9. Spray-freeze drying system for determining a spray-freeze drying endpoint according to any of claims 1-4, characterized in that the spray-freeze drying system for determining a spray-freeze drying endpoint further comprises a third temperature detection element (33) arranged in the housing (11), at least part of the third temperature detection element (33) protruding into the freeze-drying chamber.
10. Spray-freeze drying system for determining a spray-freeze drying endpoint according to any one of claims 1 to 4, wherein the control means comprises:
the receiving module is connected with the temperature detection module (30) and the pressure detection module (50) to receive data acquired by the temperature detection module (30) and the pressure detection module (50);
the calculating module is connected with the receiving module and is used for calculating the temperature difference between the bearing member (12) and the material and the pressure difference between the exhaust port and the air outlet;
the judging module is connected with the calculating module and is used for judging whether the temperature difference is smaller than a temperature preset value in a first preset time and judging whether the pressure difference is smaller than a pressure preset value in a second preset time.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202322999659.XU CN220366615U (en) | 2023-11-07 | 2023-11-07 | Spray freeze drying system for determining spray freeze drying endpoint |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202322999659.XU CN220366615U (en) | 2023-11-07 | 2023-11-07 | Spray freeze drying system for determining spray freeze drying endpoint |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN220366615U true CN220366615U (en) | 2024-01-19 |
Family
ID=89516083
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202322999659.XU Active CN220366615U (en) | 2023-11-07 | 2023-11-07 | Spray freeze drying system for determining spray freeze drying endpoint |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN220366615U (en) |
-
2023
- 2023-11-07 CN CN202322999659.XU patent/CN220366615U/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101084406B (en) | Apparatus and process for controlling the dehydration operation during a freeze-drying treatment | |
| CN107014156A (en) | Dried object moisture measurement method, Minton dryer and its control method | |
| Fissore | Freeze-drying of pharmaceuticals | |
| JP2018507478A (en) | Process monitoring and control using battery-free multipoint wireless product condition (state) sensing | |
| CN108226322A (en) | A kind of low temperature concentrating instrument and control method | |
| CN109856327B (en) | Device and method for determining water content of measured substance through humidity measurement | |
| CN103884676A (en) | Rapid detection method for contents of multi-index ingredients in traditional Chinese medicinal materials | |
| CN101793458A (en) | Vacuum freezing drying device with functions of DSC and microstructure observation | |
| CN220366615U (en) | Spray freeze drying system for determining spray freeze drying endpoint | |
| CN104266933B (en) | Device and method for on-line detection of water content of materials during vacuum drying | |
| CN105571981A (en) | Water content measuring apparatus and method | |
| CN104062201A (en) | Experimental device for measuring technological parameters of vacuum drying and vacuum freeze drying processes | |
| CN105547898A (en) | Water vapor permeability tester adopting weight-reducing method | |
| CN201673085U (en) | Quick energy-saving grain oven capable of controlling sample moisture content at drying terminals | |
| CN110470795B (en) | Drying process measuring method and device based on gas phase medium humidity measurement | |
| CN108802091A (en) | A kind of analysis experimental provision of material Airflow Drying Characteristic variation | |
| CN219758132U (en) | Quick constant temperature mirror surface condensation cavity device | |
| CN202512041U (en) | Inhalable particle online monitoring dehumidifying device | |
| CN111781228A (en) | Test device for measuring boiling point of viscous substance and application thereof | |
| CN201615678U (en) | Vacuum freeze drying device with DSC and microstructure observation functions | |
| CN114216812A (en) | Method for measuring contents of sodium carbonate and sodium bicarbonate in compound moisture retention agent | |
| CN105784753B (en) | A kind of freeze dryer eutectic point eutectic point test equipment and its test macro | |
| Rene et al. | Vacuum freeze-drying of a liquid in a vial: determination of heat and mass-transfer coefficients and optimisation of operating pressure | |
| CN111982339B (en) | Detection test paper loaded with temperature-sensitive marker, preparation method and application | |
| CN204568403U (en) | Food inspection Sample storage deep freezer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| GR01 | Patent grant | ||
| GR01 | Patent grant |