Rotary freeze-drying device for unit dose filled medicines

Abstract

The invention relates to a unit dose filled medicine rotary freeze-drying device, which comprises a filling mechanism, a bottle stopper mechanism, a rotary freezing module and a freeze-drying cabin, a combined induction heating system is arranged in the follow-up of the freeze-drying cabin, and the combined induction heating system comprises an induction heating coil and an induction heating inner component. The induction heating coil is spirally wound on the outer wall of the induction heating inner component, a penicillin bottle conveying belt is arranged in an inner cavity of the induction heating inner component, the induction heating coil is fixed to an induction heating control system alternating current power supply, and the induction heating control system alternating current power supply provides alternating current for the induction heating coil. The alternating current flowing through the induction heating coil generates an alternating magnetic field passing through the induction heating inner component, so that the induction heating inner component generates eddy current, and heating is realized. According to the invention, the continuous operation of the freeze-drying process is maintained, and meanwhile, the formation and heating of a uniform dispersion layer are realized.

Description

Technical Field

[0001] The invention belongs to the field of freeze drying, in particular to a medicine rotary freeze drying device suitable for unit dose filling of a pharmaceutical composition, a biological composition or a medical nutrition product rotary freeze drying device. Background Art

[0002] Freeze drying is a technology that dehydrates ice particles in a low-pressure environment. Freeze drying technology can make up for some of the shortcomings of drying technology. Compared with traditional drying methods, freeze drying has the advantages of maintaining the activity of biological pharmaceutical ingredients and small particles.

[0003] The freeze drying process usually involves placing a batch of dry materials in a hollow sealed chamber connected to a temperature-controlled bottom plate. During the first stage of drying, during the sublimation process, the frozen material will form a sublimation interface on the surface, and as the sublimation process proceeds, the sublimation interface moves downward and inward. Most of the free water is removed, and because it remains frozen, the material will retain a porous structure. A secondary drying is then performed to complete the freeze drying, and the temperature is increased in the secondary stage to remove the remaining bound water from the voids and remove residual moisture.

[0004] WO 2013036107 discloses a method for rotary freeze drying of unit-filled medicines, comprising: A) storing a certain amount of medicine in a water dispersion medium in at least one vial through a filling mechanism; B) rotating the vial using a rotator to form a dispersion layer attached to the inner surface circumferential wall of the vial for a period of time; C) cooling the vial and solidifying it according to step B during the rotation of the vial, especially forming ice crystals on the inner surface of the circumferential wall of the vial; D) drying the above-mentioned cooled composition by freeze drying, and during the drying, sublimating a part of the ice crystals formed in the dispersion or solution by substantially uniformly heating the circumferential wall of the vial, and the cooling and freezing of the product in the vial is achieved by applying a cold gas jet to the rotating vial, and in this process, the cooling temperature of the product can be set between 0.5 and 100°C per minute. Non-contact temperature measurement is used to control the cooling stage of the liquid and ice, and the temperature of the cooling gas and the time of a certain set value are controlled. This operation mode controls the temperature changes of the liquid phase and the crystallized water, but still needs further improvement. Goethals, W et al. describe the structure of frozen materials processed by the rotary freeze drying technique. The structure of the obtained product was visualized using micro-CT scanning technology.

[0005] However, the research and development of equipment that can perform freeze drying continuously has always been a key difficulty. Most of the current freeze drying equipment can only achieve the function of freeze drying, and cannot change the process parameters of the freezing process. It is a semi-automatic status, which has a great restriction on the development of freeze drying technology. After years of development, there is no mature continuous freeze drying equipment on the market in China, and it is impossible to carry out large-scale production.

[0006] There are still problems in developing an apparatus capable of providing a continuous freeze-drying process with a large throughput, which is not able to produce products that meet the requirements of, for example, the pharmaceutical industry. In particular, the formation of a uniformly dispersed layer and its heating while keeping the freeze-drying process running continuously remain problems. In addition, there are still problems with particle formation, which may contaminate the product and lead to a decrease in the quality of the final product.

[0007] It is therefore an object of the present invention to solve one or more of the above-mentioned problems associated with freeze drying of liquid-containing compositions in a continuous process and to further improve the methods of freezing, freeze drying and secondary drying. Summary of the invention

[0008] The purpose of the present invention is to overcome the shortcomings of the processing efficiency of the prior art and to provide a unit-dose filled medicine rotary freeze-drying device, which can achieve the formation of a uniformly dispersed layer and its heating while maintaining the continuous operation of the freeze-drying process.

[0009] The present invention solves the technical problem by the following technical solutions:

[0010] A unit-dose filled medicine rotary freeze-drying device comprises a filling mechanism, a bottle plug mechanism, a rotary freezing module and a freeze-drying chamber, wherein the filling mechanism fills a vial, and then the vial plug is pressed into the vial through the bottle plug mechanism, and the vial is freeze-dried in the freeze-drying chamber after being frozen in the rotary freezing module, and is characterized in that a combined induction heating system is subsequently arranged in the freeze-drying chamber, and the combined induction heating system comprises an induction heating coil and an induction heating internal component, the induction heating coil is spirally wound and installed on the outer wall of the induction heating internal component, a vial conveyor belt is arranged in the internal cavity of the induction heating internal component, the induction heating coil is fixed to an AC power supply of an induction heating control system, the AC power supply of the induction heating control system provides an alternating current for the induction heating coil, and the alternating current flowing through the induction heating coil generates an alternating magnetic field passing through the induction heating internal component, so that the induction heating internal component generates eddy current to achieve heating.

[0011] Moreover, connecting trays are fixed at both ends of the induction heating internal component, and the connecting trays at both ends are fixedly installed by connecting rods. An insulation layer is arranged outside the induction heating internal component, and the insulation layer is made of non-magnetic field induction and non-metallic materials such as quartz crystal, polytetrafluoroethylene or polypropylene; the connecting trays and connecting rods are also made of non-metallic materials.

[0012] Moreover, a magnetic yoke is arranged at the periphery of the induction heating coil to suppress the diffusion of magnetic lines of force.

[0013] Moreover, there are at least two combined induction heating systems, and the conveyor belts can circulate between the combined induction heating systems. A pressure sensor and a push rod system are set on the conveyor belt at the outlet end of one combined induction heating system. When the weight of a single bottle of the syringe bottle does not reach the preset weight when passing the pressure sensor, the booster of the push rod system will be pushed into the conveyor belt of another combined induction heating system for further heating. When the preset weight is reached, it will be transported out from the conveyor belt.

[0014] Moreover, a first thermal imager and a second thermal imager are respectively arranged at the inlet end and the outlet end of the combined induction heating system.

[0015] A drying method of a unit-dose filled medicine rotary freeze drying device, comprising the following steps:

[0016] 1) Filling: The filling mechanism fills the vials of unit-dose medicines. The vials enter the workstation through the conveyor belt and start to be filled with liquid. The filling mechanism performs filling, and the materials to be filled enter the bottles to be filled;

[0017] 2) Bottle plugging: The plug is positioned and pushed down into the bottle mouth by the bottle plugging mechanism, and the plug is slightly deformed and pressed into the vial. When the plug is pressed into the vial, the vial can be taken out from the bottom of the bottle plugging mechanism;

[0018] 3) Rotary freezing: The vial is positioned on the support and brought into the support platform from the side. A rotator is set in the rotary freezing module, which rotates around the rotation axis and isolates the rotary freezing module from the external environment to form a vacuum low-pressure environment;

[0019] 4) Freeze drying: The vials enter the freeze drying chamber and are freeze dried in a vacuum low-pressure environment until the freeze drying is completed. They are then sent out of the freeze drying chamber via a conveyor belt and enter the combined induction heating system for the second stage of induction heating drying.

[0020] 5) Turn on the cooling function of the induction heating control system: turn on the transmission belt and set the induction heating control system to the cooling function, that is, slowly increase the power to avoid the induction heating internal components heating up too fast and causing damage to the material components;

[0021] 6) The induction heating control system starts the heating function: the induction heating function of the induction heating control system is turned on: the current flows into the induction coil through the induction heating control system, and the induction heating internal components generate heat under the action of the alternating electric field;

[0022] 7) Heat treatment: cyclic heating treatment under the continuous transmission mode of conveyor belt;

[0023] 8) End: Finally, the vial is sent out from the combined induction heating system.

[0024] The advantages and beneficial effects of the present invention are:

[0025] 1. The unit-dose liquid high-speed filling device of the present invention is a rotary freeze-drying device, and a combined induction heating system is subsequently arranged in the freeze-drying chamber to improve the heating efficiency, so as to quickly increase the temperature of the flowing liquid and improve the uniformity of the temperature distribution in the vial.

[0026] 2. The unit dose liquid high speed filling device of the present invention is a rotary freeze drying device, which is a device for freeze drying a liquid containing a composition in a continuous process, and the device is capable of processing at least about 4000 30R vials per day.

[0027] 3. The unit-dose liquid high-speed filling device and the rotary freeze-drying device of the present invention are used to freeze-dry the liquid containing the composition in a continuous process, and provide a control mechanism in the freezing or drying step to allow the freezing or sublimation speed to be adjusted, so that both freezing and drying are controlled. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is a schematic diagram of the structure of the unit-dose liquid high-speed filling rotary freeze-drying device of the present invention;

[0029] Figure 2 It is a schematic structural diagram of a combined induction heating system of a unit-dose liquid high-speed filling rotary freeze-drying device of the present invention;

[0030] Figure 3 for Figure 2 A side view schematic diagram of

[0031] Figure 4 A schematic structural diagram of an induction heating sensor of the present invention.

[0032] Figure 5 A temperature map of the outer surface of the container wall "measured" by the first thermal imager of the present invention.

[0033] Description of Reference Numerals

[0034] 1-syringa bottle; 2-induction heating control system; 3-first thermal imager; 4-connecting rod; 5-combined induction heating system; 6-induction heating coil; 7-insulation layer; 8-conveyor belt; 9-booster; 10-push rod system; 11-pressure sensor; 12-connecting tray; 13-connecting column; 14-rotator; 15-support platform; 16-filling mechanism; 17-bottle plug mechanism; 18-rotating freezing module; 19-freeze drying chamber; 20-induction heating drying chamber; 21-induction heating internal components; 22-second thermal imager. DETAILED DESCRIPTION

[0035] The present invention is further described in detail below through specific examples. The following examples are only illustrative and not restrictive, and the protection scope of the present invention cannot be limited thereto.

[0036] A unit-dose filled drug rotary freeze drying device comprises a filling mechanism 16, a bottle plug mechanism 17, a rotary freezing module 18 and a freeze drying chamber 19. The filling mechanism 16 fills a vial 1, and then the vial plug is pressed into the vial 1 through the bottle plug mechanism 17. The vial 1 is frozen in the rotary freezing module 18 and then freeze dried in the freeze drying chamber 19. The freeze drying chamber 19 is subsequently provided with a combined induction heating system 5, which comprises an induction heating drying chamber 20, an induction heating coil 6, and an induction heating internal component 21. The induction heating coil 6 is spirally wound and installed on the outer wall of the induction heating internal component 21. A vial 1 conveyor belt 8 is arranged in the inner cavity of the induction heating internal component 21. The induction heating coil 6 is fixed to an AC power supply of an induction heating control system 2. The AC power supply of the induction heating control system 2 provides an alternating current for the induction heating coil 6. The induction heating coil 6 is connected to the AC power supply of the induction heating control system through a wire, and the wire can be supported and installed through a connecting rod 4. The alternating current flowing through the induction heating coil 6 generates an alternating magnetic field passing through the induction heating internal component 21, causing the induction heating internal component 21 to generate eddy currents, thereby achieving heating.

[0037] The two ends of the induction heating inner component 21 are fixed with connecting trays 12, and the connecting trays 12 at the two ends are fixedly installed through connecting columns 13. A heat preservation layer 7 is arranged outside the induction heating inner component 21, and the heat preservation layer 7 is made of non-magnetic field induction and non-metallic materials such as quartz silin, polytetrafluoroethylene or polypropylene; the connecting trays 12 and the connecting columns 13 are also made of non-metallic materials. A magnetic yoke is arranged around the induction heating coil 6 to suppress the diffusion of magnetic lines of force.

[0038] In this embodiment, there are at least two combined induction heating systems, and the conveyor belts are cyclically arranged. The conveyor belt 8 can circulate between the combined induction heating systems 5. A pressure sensor 11 and a push rod system 10 are arranged on the conveyor belt 8 at the outlet end of one combined induction heating system 5. When passing through the pressure sensor 11, when the weight of a single bottle of the vial 1 does not reach the preset mass, the booster 9 of the push rod system 10 will be pushed into the conveyor belt 8 of another combined induction heating system 5 for continued heating. When the preset mass is reached, it will be transported out from the conveyor belt 8.

[0039] A first thermal imager 3 and a second thermal imager 22 are respectively arranged at the inlet and outlet of the combined induction heating system 5 to measure the temperature of the vials at the inlet and outlet ends in real time, thereby adjusting and controlling the temperature of the combined induction heating system.

[0040] A drying method of a unit-dose filled medicine rotary freeze drying device, comprising the following steps:

[0041] 1) Filling: The filling mechanism 16 fills the vial 1 of the unit dose filled medicine. The vial 1 enters the work station through the conveyor belt 8 and starts to be filled with liquid. The filling mechanism 16 performs filling, and the material to be filled enters the bottle to be filled;

[0042] 2) Bottle plugging: The plug is positioned and pushed downward into the bottle mouth by the bottle plugging mechanism 17, and the plug is slightly deformed and pressed into the vial 1. When the plug is pressed into the vial, the vial can be taken out from below the bottle plugging mechanism 17;

[0043] 3) Rotary freezing: The vial is positioned on the support and brought into the support platform 15 from the side. A rotator 14 is provided on the rotary freezing module 18. The rotator 14 rotates around the rotation axis and isolates the rotary freezing module 18 from the external environment to form a vacuum low-pressure environment.

[0044] 4) Freeze drying: The vials 1 enter the freeze drying chamber 19 and are freeze dried in a vacuum low pressure environment until the freeze drying is completed. The vials 1 are then sent out of the freeze drying chamber 19 via the conveyor belt 8 and enter the combined induction heating system 5 for the second stage of induction heating drying.

[0045] 5) Turn on the cooling function of the induction heating control system 2: Turn on the transmission belt and set the induction heating control system 2 to the cooling function, that is, slowly increase the power to avoid the induction heating internal component 21 heating up too quickly and causing damage to the material components;

[0046] 6) The induction heating control system 2 starts the heating function: the induction heating function of the induction heating control system 2 is turned on: the current flows into the induction coil through the induction heating control system 2, and the induction heating internal component 21 generates heat under the action of the alternating electric field;

[0047] 7) Heat treatment: cyclic heating treatment is performed in the continuous transmission mode of the conveyor belt 8;

[0048] 8) End: Finally, the vial 1 is sent out from the combined induction heating system 5 .

[0049] In the continuous transmission mode, the first thermal imager 3 located at the entrance of the induction heating coil 6 determines the temperature and then heats it. During the transmission process, the second thermocouple measures the temperature and determines that the liquid temperature reaches the set value. When the set value is reached, the induction heating control system 2 reduces the power for heat preservation, and heats it during the forward transmission process of the conveyor belt 8. After exiting the induction heating coil 6, the processed material is obtained.

[0050] The continuous working mode is that the vial 1 enters the induction heating range, the push rod system 10 is parameterized, and when passing the pressure sensor 1, if the weight of a single bottle does not reach the preset weight, it will be pushed into another induction heating conveyor belt 8 by the booster 9 for further heating. When the preset weight is reached, it will be transported out from the conveyor belt 8.

[0051] After being frozen, the composition containing the liquid is at least partially sublimated. In order to uniformly heat the vial, heat should be provided to the entire circumference of the vial. Placing the vial in a heating jacket or a chamber with a surrounding infrared radiator will seriously hinder the continuous movement of the vial during the continuous freeze-drying process. As a result, the vial will remain in the heating jacket or infrared heating chamber until the sublimation or desorption process is completed, and the vial in the jacket is generally not able to be evaluated by an optical measurement system, thereby hindering the feedback controlled heating of the vial. Therefore, the induction heating device of the rotary freeze-drying device for unit-dose filling of medicines, by designing a new type of induction heating internal component 21, makes the temperature distribution of the heating process more uniform and improves the heating efficiency.

[0052] Although the embodiments and drawings of the present invention are disclosed for illustrative purposes, those skilled in the art will appreciate that various substitutions, changes and modifications are possible without departing from the spirit and scope of the present invention and the appended claims. Therefore, the scope of the present invention is not limited to the contents disclosed in the embodiments and drawings.

Claims

1. A unit-dose filled drug rotary freeze-drying device, comprising a filling mechanism (16), a bottle plug mechanism (17), a rotary freezing module (18) and a freeze-drying chamber (19), wherein the filling mechanism (16) fills a vial (1), and then the vial plug is pressed into the vial (1) through the bottle plug mechanism (17), and the vial (1) is frozen in the rotary freezing module (18) and then freeze-dried in the freeze-drying chamber (19), characterized in that: The freeze drying chamber (19) is subsequently provided with a combined induction heating system (5), which comprises an induction heating coil (6) and an induction heating internal component (21). The induction heating coil (6) is spirally wound and installed on the outer wall of the induction heating internal component (21). A conveyor belt (8) for the vial (1) is arranged in the inner cavity of the induction heating internal component (21). The induction heating coil (6) is fixed to an AC power supply of an induction heating control system (2). The AC power supply of the induction heating control system (2) provides an alternating current to the induction heating coil (6). The alternating current flowing through the induction heating coil (6) generates an alternating magnetic field passing through the induction heating internal component (21), so that the induction heating internal component (21) generates eddy currents, thereby achieving heating.

2. The unit dose filled drug rotary freeze drying device according to claim 1, characterized in that: The two ends of the induction heating inner component (21) are fixed with connection trays (12), and the connection trays (12) at the two ends are fixedly installed through connection columns (13). A thermal insulation layer (7) is arranged outside the induction heating inner component (21), and the thermal insulation layer (7) is made of non-magnetic field induction and non-metallic materials such as quartz, polytetrafluoroethylene or polypropylene; the connection trays (12) and the connection columns (13) are also made of non-metallic materials.

3. The unit dose filled drug rotary freeze drying device according to claim 1, characterized in that: A magnetic yoke is arranged on the periphery of the induction heating coil (6) to suppress the diffusion of magnetic lines of force.

4. The unit-dose filled drug rotary freeze-drying device according to claim 1, characterized in that: There are at least two combined induction heating systems (5), and the conveyor belt (8) can circulate between the combined induction heating systems (5). A pressure sensor (11) and a push rod system (10) are arranged on the conveyor belt (8) at the outlet end of one combined induction heating system (5). When the weight of a single bottle of the vial (1) does not reach a preset weight when passing through the pressure sensor (11), the booster (9) of the push rod system (10) is pushed into the conveyor belt (8) of another combined induction heating system (5) to continue heating. When the preset weight is reached, the bottle is transported out from the conveyor belt (8).

5. The unit-dose filled drug rotary freeze-drying device according to claim 1, characterized in that: A first thermal imager (3) and a second thermal imager (22) are respectively arranged at the inlet end and the outlet end of the combined induction heating system (5).

6. A method for drying a unit-dose filled drug rotary freeze-drying device, characterized in that: It includes the following steps: 1) Filling: The filling mechanism (16) fills the vial (1) of the unit dose filled medicine. The vial (1) enters the work station through the conveyor belt (8) and starts to be filled with liquid. The filling mechanism (16) performs filling, and the material to be filled enters the bottle to be filled; 2) Bottle plugging: The plug is positioned and pushed downward into the bottle mouth by the bottle plugging mechanism (17), and the plug is slightly deformed and pressed into the vial (1). When the plug is pressed into the vial, the vial can be taken out from below the bottle plugging mechanism (17); 3) Rotary freezing: The vial is positioned on the support and brought into the support platform (15) from the side. A rotator (14) is arranged on the rotary freezing module (18). The rotator (14) rotates around the rotation axis and isolates the rotary freezing module (18) from the external environment to form a vacuum low-pressure environment. 4) Freeze drying: the vial (1) enters the freeze drying chamber (19) and is freeze dried in a vacuum low pressure environment until the freeze drying is completed. The vial is then sent out of the freeze drying chamber (19) via a conveyor belt (8) and enters the combined induction heating system (5) to undergo a second stage of induction heating drying; 5) The induction heating control system (2) turns on the cooling function: the transmission belt is turned on, and the induction heating control system (2) is set to the cooling function, that is, the power is slowly increased to avoid the induction heating internal component (21) from heating up too quickly and causing damage to the material components; 6) The induction heating control system (2) starts the heating function: the induction heating function of the induction heating control system (2) is turned on: the current flows into the induction coil through the induction heating control system (2), and the induction heating internal component (21) generates heat under the action of the alternating electric field; 7) Heat treatment: cyclic heating treatment is performed in a continuous transmission mode of a conveyor belt (8); 8) End: Finally, the vial (1) is sent out from the combined induction heating system (5).

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