JP7390176B2 - Vacuum drying equipment, how to adjust the temperature of shelves in vacuum drying equipment - Google Patents

Description

TECHNICAL FIELD The present invention relates to a vacuum drying device and a method for adjusting the temperature of a shelf in a vacuum drying device.

2. Description of the Related Art Freeze-drying state monitoring devices have been known, for example, as described in Patent Document 1 below.

Japanese Patent Application Publication No. 2015-31486

By the way, in the freeze-drying state monitoring device as described above, the material to be dried (material to be dried) is dried by circulating a heat medium through a shelf board on which the material to be dried is placed. The dry state of the material to be dried can be determined, for example, by the following methods (1) and (2).
(1) The temperature detected by the first temperature sensor that detects the temperature of the heat medium on the inlet side of the shelf board and the temperature detected by the second temperature sensor that detects the temperature of the heat medium on the outlet side of the shelf board are approximately the same temperature. The drying state of the material to be dried is ascertained on the assumption that the shelf temperature is the same as the medium temperature and the temperature of the material to be dried is also the same.
(2) Detect the minute temperature difference between the heat medium temperature on the inlet side and the outlet side of the heat medium, and check the drying state of the material to be dried on the premise that the amount of heat based on this temperature difference is all used for sublimation. grasp.
In this way, in understanding the drying state of the material to be dried, the product temperature is not measured directly as a physical quantity, but indirectly. Indirect measurements are calculated by converting using multiple components (physical quantities) and assumptions, and naturally the error tends to increase depending on the number of components, the types of components, and the correlation between each component.

The present invention has been made in view of the above-mentioned circumstances, and it is an object of the present invention to more accurately grasp the drying state of a material to be dried, particularly the sublimation surface temperature.

In order to solve the above problems, the present invention proposes the following means.
The vacuum drying apparatus according to the present invention includes a drying chamber, a shelf arranged in the drying chamber on which objects to be dried are placed, a fluid cylinder that raises and lowers the shelf, and a fluid cylinder that supplies and discharges fluid to and from the fluid cylinder. a fluid supply/drainage system that measures the temperature of the shelf; a measurement unit that is provided in the fluid supply/drainage system and measures the fluid pressure of the fluid; a collection unit that collects moisture sublimed from the dried material ; The measuring device includes an adjustment section that performs adjustment, and a control section that controls the adjustment section based on the measurement result of the measurement section .

In this invention, when the dried material placed on the shelf in the drying chamber dries, its weight decreases. When the weight of the items to be dried decreases, the total weight of the items to be dried and the shelf on which the items are placed also decreases. As the combined weight of the items to be dried and the shelf decreases, the downward gravitational force exerted by the shelf on the fluid cylinder supporting the shelf to raise and lower the shelf also decreases. This changes the fluid pressure within the fluid cylinder. Since the measuring section measures the fluid pressure supplied to and discharged from the fluid cylinder, it is possible to detect a decrease in weight of the object to be dried due to drying based on a change in the measurement result in the measuring section. There is a direct correlation between the change in weight of the material to be dried as it dries and the change in fluid pressure in the fluid cylinder. Therefore, it is possible to directly detect the drying state of the object to be dried and to grasp the drying state of the object to be dried with higher precision.

In this case, based on the measurement results of the measurement unit, that is, the changes in the fluid pressure of the fluid cylinder, it is possible to understand the change in weight of the object to be dried as it dries. As a result, the control unit adjusts the temperature of the shelf in the adjustment unit based on the change in the fluid pressure of the fluid cylinder, so that the temperature of the shelf for drying the item to be dried is adjusted according to the drying state of the item to be dried. can be adjusted appropriately.

Further, the control unit converts the measurement results of the measuring unit into the weight of the shelf supporting the drying material at two different times, and calculates the weight of the drying material from the difference between these two times and the weight. Calculate the sublimation rate of the dried material, calculate the estimated temperature of the dried material based on the sublimation rate, and control the adjustment unit so that the estimated temperature is equal to or less than a preset threshold. Good too.

In this case, the dead weight of the shelf is known. For this reason, the weight of the shelf that supports the items to be dried, that is, the total weight of the weight of the items to be dried and the shelf's own weight, must be calculated from the measurement result of the fluid pressure of the fluid cylinder, which is the measurement result of the measurement unit. Therefore, changes in the drying state of the material to be dried can be understood as the sublimation rate. From this sublimation rate, the temperature of the material to be dried can be estimated. Therefore, the temperature of the shelf can be appropriately adjusted depending on the drying state of the material to be dried.

Further, the material to be dried is placed on the shelf while being housed in a container, and the control unit controls the latent heat of sublimation of the material to be dried, the sublimation rate, the cross-sectional area of the container, and the conduction of the container. The estimated temperature may be calculated based on a thermal coefficient.
Note that examples of containers include vials, trays, syringes, ampoules, and the like.

In this case, the temperature of the material to be dried is estimated with high accuracy by calculating the estimated temperature of the material to be dried based on the latent heat of sublimation of the material to be dried, the sublimation rate, the cross-sectional area of the container, and the heat transfer coefficient of the container. be able to. This makes it possible to accurately adjust the temperature of the shelf according to the temperature state of the items to be dried, and to dry the items to be dried under appropriate conditions.

Further, the item to be dried is placed on the shelf while being housed in a container, and the control unit controls the internal pressure of the drying chamber, the water vapor movement resistance of the item to be dried, and the product breakage in the container. The estimated temperature may be calculated based on the area and the sublimation rate.

In this case, the temperature of the material to be dried can be determined with high accuracy by calculating the estimated temperature of the material to be dried based on the internal pressure of the drying chamber, the water vapor transfer resistance of the material to be dried, the cross-sectional area of the product in the container, and the sublimation rate. It can be estimated that Therefore, it is possible to accurately adjust the temperature of the shelf according to the temperature state of the material to be dried, and the material to be dried can be dried under appropriate conditions.

Further, the threshold value may be a collapse temperature.

In this case, when the temperature of the material to be dried exceeds the collapse temperature, a collapse phenomenon occurs in which the portion of the material to be dried where the water is frozen contracts, and the material to be dried cannot be dried properly. By appropriately adjusting the temperature of the shelf based on changes in the fluid pressure of the fluid cylinder and maintaining the temperature of the dried material below the collapse temperature, the material to be dried can be dried well. .

A method for adjusting the temperature of a shelf in a vacuum drying apparatus according to the present invention includes a drying chamber, a shelf disposed in the drying chamber on which an object to be dried is placed, a fluid cylinder that raises and lowers the shelf, and the object to be dried. A method for adjusting the temperature of the shelf in a vacuum drying apparatus comprising: a collection unit that collects moisture sublimed from the fluid cylinder; and adjusting the temperature of the shelf based on the fluid pressure of the shelf.

In this invention, when the dried material placed on the shelf in the drying chamber dries, its weight decreases. When the weight of the items to be dried decreases, the total weight of the items to be dried and the shelf on which the items are placed also decreases. As the combined weight of the items to be dried and the shelf decreases, the downward gravitational force exerted by the shelf on the fluid cylinder supporting the shelf to raise and lower the shelf also decreases. This changes the fluid pressure within the fluid cylinder. Therefore, based on the fluid pressure of the fluid in the fluid supply/drainage system that supplies fluid to the fluid cylinder, it is possible to grasp the weight reduction due to drying of the object to be dried. There is a direct correlation between the change in weight of the material to be dried as it dries and the change in fluid pressure in the fluid cylinder. Therefore, it is possible to more directly detect the drying state of the material to be dried, and to grasp the drying state of the material to be dried with higher precision.

Further, at each of two different times, the fluid pressure is converted into the weight of the shelf supporting the object to be dried, and the sublimation rate of the object to be dried is calculated from the difference between these two times and weights. The estimated temperature of the material to be dried may be calculated based on the sublimation rate, and the temperature of the shelf may be controlled so that the estimated temperature is equal to or less than a preset threshold.

In this case, since the weight of the shelf is known, from the fluid pressure of the fluid in the fluid supply/discharge system that supplies fluid to the fluid cylinder, the weight of the shelf supporting the drying object, that is, the total weight of the drying object and the shelf. By converting and determining the change in the drying state of the material to be dried, it is possible to understand the change in the drying state of the material to be dried as the sublimation rate. From this sublimation rate, the temperature of the material to be dried can be estimated. Therefore, the temperature of the shelf can be appropriately adjusted depending on the drying state of the material to be dried.

A method for adjusting the temperature of a shelf in a vacuum drying apparatus according to the present invention includes a drying chamber, a shelf arranged in the drying chamber on which an object to be dried is placed, and a trap for collecting moisture sublimed from the object to be dried. A method for adjusting the temperature of the shelf in a vacuum drying apparatus comprising a collecting section, the method comprising: measuring the weight of the shelf supporting the dried material at two different times; The sublimation rate of the object to be dried is calculated from each difference in weight, and the estimated temperature of the object to be dried is calculated based on the sublimation rate. Adjust shelf temperature.

In this invention, when the dried material placed on the shelf in the drying chamber dries, its weight decreases. When the weight of the items to be dried decreases, the total weight of the items to be dried and the shelf on which the items are placed also decreases. Thereby, the drying state of the object to be dried can be determined as the sublimation rate from the weight of the shelf supporting the object to be dried. From this sublimation rate, the temperature of the material to be dried can be estimated. Therefore, it is possible to more directly detect the drying state of the material to be dried, and to grasp the drying state of the material to be dried with higher precision.

Further, the material to be dried is placed on the shelf while being housed in a container, and the temperature is determined based on the latent heat of sublimation of the material to be dried, the sublimation rate, the cross-sectional area of the container, and the heat transfer coefficient of the container. , the estimated temperature may be calculated.

In this case, the temperature of the dried material can be estimated with high accuracy by calculating the estimated temperature of the dried material based on the sublimation latent heat of the dried material, the sublimation rate, the cross-sectional area of the container, and the heat transfer coefficient of the container. Can be done. This makes it possible to accurately adjust the temperature of the shelf according to the temperature state of the material to be dried, and to dry the material to be dried under appropriate conditions.

Further, the material to be dried is placed on the shelf while being housed in a container, the internal pressure of the drying chamber, the water vapor movement resistance of the material to be dried, the cross-sectional area of the product in the container, the sublimation rate, and the like. The estimated temperature may be calculated based on.

In this case, the temperature of the material to be dried can be determined with high accuracy by calculating the estimated temperature of the material to be dried based on the internal pressure of the drying chamber, the water vapor transfer resistance of the material to be dried, the cross-sectional area of the product in the container, and the sublimation rate. It can be estimated that Therefore, it is possible to accurately adjust the temperature of the shelf according to the temperature state of the material to be dried, and the material to be dried can be dried under appropriate conditions.

Further, the threshold value may be a collapse temperature.

In this case, when the temperature of the material to be dried exceeds the collapse temperature, a collapse phenomenon occurs in which the portion of the material to be dried where the water is frozen contracts, and the material to be dried cannot be dried properly. By appropriately adjusting the temperature of the shelf based on changes in the fluid pressure of the fluid cylinder and maintaining the temperature of the dried material below the collapse temperature, the material to be dried can be dried well. .

According to the present invention, the drying state of the object to be dried can be detected more directly, and in particular, the sublimation surface temperature, which indicates the drying state of the object to be dried, can be grasped with higher precision.

1 is a diagram showing a schematic configuration of a vacuum drying apparatus according to an embodiment of the present invention. FIG. 2 is a cross-sectional view showing a container placed on a shelf of the vacuum drying apparatus shown in FIG. 1 and accommodating an object to be dried. It is a block diagram showing the functional composition of the control part of the vacuum drying device concerning one embodiment of the present invention. It is a flowchart which shows the flow of the temperature adjustment method of the shelf in the vacuum drying apparatus based on one Embodiment of this invention.

EMBODIMENT OF THE INVENTION Hereinafter, with reference to drawings, the vacuum drying apparatus and the temperature adjustment method of the shelf in a vacuum drying apparatus which concern on one Embodiment of this invention are demonstrated.
A vacuum drying apparatus 1 shown in FIG. 1 is used to freeze and vacuum dry a raw material liquid, for example, in order to manufacture medicines, pharmaceutical preparations, and raw materials thereof. The raw material liquid is stored in the container 100 as the material to be dried F, and is frozen in the previous step and is in a solid state (usually in the form of a lump, but other forms include spongy and powdery forms). The vacuum drying apparatus 1 mainly includes a drying chamber 10, a collection section 20, and a control section 40. In this example, the container 100 is exemplified as a vial shape and will be explained later, but the container shape can be changed to a tray, a syringe, an ampoule, etc. depending on the purpose of production.

The drying chamber 10 is a space for vacuum drying the material to be dried F. The room temperature and internal pressure (degree of vacuum) of the drying chamber 10 are controlled. The degree of vacuum in the drying chamber 10 can be adjusted within a range of, for example, 5 to 300 [Pa]. The temperature and degree of vacuum (internal pressure) in the drying chamber 10 are each measured by sensors (not shown). The sensor sends the measurement results to the control unit 40 and provides feedback such as changing the exhaust speed of the drying chamber 10, so that the internal pressure of the drying chamber 10 is adjusted to the desired internal pressure.
In the drying chamber 10, a shelf 11 is provided on which objects to be dried F are placed. The shelf 11 includes a plurality of shelf boards 11a spaced apart in the vertical direction. A plurality of containers 100 containing items to be dried F are placed on each shelf board 11a.

The shelf 11 is provided with an adjustment section 12 that adjusts its temperature. The adjustment unit 12 adjusts the heating temperature of the material to be dried F placed on the shelf board 11a by, for example, circulating a medium through a medium flow path 11b provided inside the shelf board 11a. Oil containing silicone as a main component is usually used as the heat medium. The heat medium generally has a temperature range of -80°C to +150°C. Furthermore, if the performance at sub-zero temperatures is not a concern, such as when the medium does not need to be used for the purpose of freezing in the previous step, a medium mainly composed of water is used as the heat medium. Of course, if an inhibitor is added, even a medium mainly composed of water can be used under the conditions of an antifreeze solution.

The adjustment section 12 mainly includes a heat medium supply source 13, a supply pump (not shown), a heat medium supply pipe 14, a supply side header 15, a recovery side header 16, a heat medium recovery pipe 17, and a heat medium recovery section 18. There is. The heat medium supply source 13 is a so-called chiller (heat medium circulation device). The heat medium supply source 13 includes (1) a heat source such as a heater (not shown) that heats the heat medium, or (2) a heat source and a heat removal source. A supply pump (not shown) sends the heat medium from the heat medium supply source 13 to the heat medium supply pipe 14 .

The heat medium sent out to the heat medium supply pipe 14 is supplied to the medium flow path 11b of each shelf board 11a via the supply side header 15 and the supply side branch pipe 15s. The material to be dried F accommodated in the container 100 placed on the shelf board 11a is heated by the heat medium supplied to the medium flow path 11b. The heat medium that has passed through the medium flow path 11b is recovered by the heat medium recovery section 18 via the recovery side branch pipe 16s, the recovery side header 16, and the heat medium recovery pipe 17.

The heat medium supply pipe 14 is provided with a supply side temperature sensor 19A that detects the temperature of the heat medium supplied to the medium flow path 11b. The heat medium recovery pipe 17 is provided with a recovery side temperature sensor 19B that detects the temperature of the heat medium recovered from the medium flow path 11b. Note that the supply-side temperature sensor 19A and the recovery-side temperature sensor 19B may be replaced by sensors built in the heat medium supply source 13 and having the same purpose.

The heating medium supply operation in the adjustment section 12 is controlled by the control section 40 . Specifically, the control unit 40 controls the operation of a heater (not shown) that heats the heat medium in the heat medium supply source 13 and the operation of a supply pump that delivers the heat medium. The control unit 40 controls the temperature and flow rate of the heat medium supplied to the medium flow path 11b, for example, based on the average value of the measurement value of the supply-side temperature sensor 19A and the measurement value of the recovery-side temperature sensor 19B. Moreover, the control part 40 controls the supply operation of the heat medium in the adjustment part 12 based on the temperature of the to-be-dried material F, as described in detail later. Note that the series of temperature and flow rate controls of the heat medium may be performed by a control section (not shown) built in the heat medium supply source 13, and the control section 40 may be configured to provide only the target temperature value to the heat medium supply source 13.

Here, as shown in FIG. 2, the container 100 containing the material to be dried F has a bottomed shape and has an opening 101 that opens upward. A predetermined amount of the material to be dried F is stored in a container 100 in a pre-process of the vacuum drying apparatus 1. A stopper (not shown) is set in the opening 101 of the container 100 in advance. In an open state where a stopper (not shown) is set in the opening 101, the inside of the container 100 communicates with the outside, and water (steam) sublimated from the material to be dried F flows out of the container 100. Note that, as will be described later, the atmosphere of the stopper is separated (closed) at the opening 101 by the shelf plate moving mechanism. Therefore, the relative position of the stopper with respect to the container 100 is such that the atmosphere can be separated when the stopper is closed, and water can flow out when the stopper is opened.

As shown in FIG. 1, the shelf 11 is equipped with the following mechanism in order to close the opening 101 of the container 100 with a stopper (not shown) after vacuum drying the material to be dried F in the container 100. .
The plurality of shelf boards 11a of the shelf 11 can be moved up and down in the vertical direction by a shelf moving mechanism (not shown), and the interval between the shelf boards 11a located above and below each other can be increased or decreased. At the top of the shelf 11, a fluid cylinder 30 is provided for raising and lowering the plurality of shelf boards 11a to increase or decrease the interval between them.

The fluid cylinder 30 is expanded and contracted in the vertical direction by fluid pressure such as hydraulic oil and hydraulic air. Note that, for reasons explained later, it is desirable that the fluid be incompressible. Therefore, it is desirable to select a highly incompressible fluid (for example, oil or water) as the fluid. In this embodiment, as the fluid cylinder 30, for example, a hydraulic cylinder operated by the fluid pressure of hydraulic oil is used. The fluid cylinder 30 includes a cylinder body 31 fixed to the drying chamber 10 and a rod 32 that extends and contracts downward with respect to the cylinder body 31. Inside the cylinder body 31, an expansion side oil chamber 31a and a contraction side oil chamber 31b are formed by being partitioned by a piston 32p provided at the base end of the rod 32.

A fluid supply/discharge system 35 is connected to the fluid cylinder 30 for supplying and discharging fluid (hydraulic oil) from a fluid supply source 33 to the cylinder body 31 of the fluid cylinder 30 . The fluid supply/drainage system 35 includes an expansion side pipe 36 and a contraction side pipe 37.

When fluid is supplied from the fluid supply source 33 to the expansion side oil chamber 31a in the cylinder body 31 through the expansion side piping 36, the piston 32p is pressed downward within the cylinder body 31. As a result, the rod 32 protrudes downward from the cylinder body 31, and the fluid cylinder 30 extends downward. As the rod 32 protrudes downward, the fluid in the contraction side oil chamber 31b in the cylinder body 31 returns to the fluid supply source 33 through the contraction side piping 37.

When fluid is supplied from the fluid supply source 33 to the contraction side oil chamber 31b inside the cylinder body 31 through the contraction side piping 37, the piston 32p is pressed upward within the cylinder body 31. As a result, the rod 32 moves upward and the downward protrusion from the cylinder body 31 becomes smaller. In this way, the fluid cylinder 30 is shortened upwardly. At this time, as the rod 32 moves upward, the fluid in the extension oil chamber 31a in the cylinder body 31 returns to the fluid supply source 33 through the extension pipe 36.

The operation of the fluid supply source 33 of the fluid cylinder 30 is controlled by a control section 40. For this reason, the growth side pipe 36 is provided with a growth side pressure sensor 38 that measures the fluid pressure P1 of the fluid in the growth side pipe 36. The contraction side piping 37 is provided with a contraction side pressure sensor 39 (measuring section) that measures the fluid pressure P2 of the fluid in the contraction side piping 37. By the way, to explain the time-series transition of the fluid pressure during the expansion/contraction operation of the fluid cylinder 30, in the configuration of the present application, ideally, the fluid pressure P2 does not vary during both the expansion and contraction. The reason for this is that the fluid cylinder 30 is configured so that nothing other than the gravity of the suspended structure acts on the fluid pressure P2 (the fluid pressure P1 in this ideal state is zero). In reality, the fluid pressure P2 is influenced by the movement resistance of the medium, the bending resistance of the supply side branch pipe 15s and the recovery side branch pipe 16s, the fluid pressure P1 existing in the opposing cylinder, and the like. Therefore, it is necessary to add a force corresponding to these forces to the fluid pressure P2. However, at the time of stoppage or minute movement, components other than the fluid pressure P1 can be ignored. Therefore, the fluid pressure P2 can be treated as being equal to the gravity of the structure suspended by the fluid cylinder 30.

When the fluid cylinder 30 is extended under the control of the control unit 40, all of the shelf boards 11a other than the lowest shelf board 11a among the plurality of shelf boards 11a are further moved downward, and are positioned above and below each other. This results in a situation in which the distance between the shelf boards 11a decreases. As a result, among the shelf boards 11a located above and below each other, the stopper (not shown) set in the opening 101 of the container 100 placed on the shelf board 11a located below is connected to the shelf board 11a located above. After contacting with the lower surface of the plate 11a, it is pressed downward. Hereinafter, this step will be referred to as a pressing operation to distinguish it from a stretching operation. As a result, a stopper (not shown) is pushed into the opening 101 of the container 100, and the opening 101 is closed. To explain the time-series transition of the fluid pressure during this pressing operation, in the configuration of the present application, ideally the fluid pressure P1 is generated only during the pressing operation, and during other expansion and contraction operations, the fluid pressure P1 is It becomes zero. In other words, the fluid cylinder 30 can stand still if it generates a reaction force equivalent to the gravity of the suspended structure, and can also be configured to move when the fluid cylinder 30 is extended (moved downward in the direction of gravity). The gravity of the object can be used, and the fluid pressure P1 is not required. However, during the pressing operation, it is necessary to generate a pushing force to close the plurality of stoppers into the openings 101 of the plurality of containers 100. At this time, the fluid pressure P1 is adjusted to provide the necessary pushing force. In this embodiment, all the valves are closed when the fluid pressure P1 reaches about 10 times the gravity of the suspended structure.
After closing, by shortening the fluid cylinder 30, all the other shelf boards 11a except the lowest shelf board 11a are moved upward and returned to their original positions, and the shelf boards 11a located above and below each other are Increase the spacing.

The collecting unit 20 collects water sublimated from the material to be dried F in the drying chamber 10. The collection section 20 has a communication port 21 that communicates with the interior of the drying chamber 10 . Thereby, the collection section 20 is connected to the drying chamber 10. The collection section 20 is provided with a vacuum pump 22 that evacuates the inside of the collection section 20 .

A cold trap 23 is provided within the collection section 20 . The cold trap 23 has a tube shape through which a cooling medium supplied from a cooling medium supply source (not shown) flows. The flow of the cooling medium to the cold trap 23 is controlled by the control unit 40. Note that, as the cooling medium, for example, fluorocarbon gas R404A, silicone oil, etc. can be used.

The cold trap 23 is cooled by flowing a cooling medium under the control of the control unit 40 . The surface of the cold trap 23 is cooled to a temperature at which most of the water vapor sublimated from the material to be dried F in the drying chamber 10 can be condensed and collected. Note that the temperature of the cold trap 23 is appropriately set depending on the type of the material to be dried F, the ultimate pressure of the drying chamber 10, and the like. In this way, the cold trap 23 cools the inside of the collection section 20 and condenses and collects the water sublimed from the material to be dried F.

A gate valve 24 is provided in the communication port 21 of the collection section 20 . The gate valve 24 includes a partition body 24a that can close the communication port 21, a drive cylinder 24b that moves the partition body 24a back and forth with respect to the communication port 21, and a drive source 24c that drives the drive cylinder 24b. The driving cylinder 24b is moved forward and backward through the partition body 24a with respect to the communication port 21 by controlling the drive source 24c to be driven by the control unit 40. When the partition body 24a is retracted from the communication port 21, the drying chamber 10 and the collection section 20 communicate with each other through the communication port 21. When the partition body 24a is moved forward to close the communication port 21, the drying chamber 10 and the collection section 20 are cut off.

In the vacuum drying apparatus 1 described above, the material to be dried F is vacuum dried in the following manner.

First, the material to be dried F is carried into the drying chamber 10 from a loading/unloading chamber (not shown).
Next, after the drying chamber 10 and the loading/unloading chamber are atmospherically separated under the control of the control unit 40, heat is removed using the heat medium supply source 13 so that the material to be dried F is frozen. The heat removal path is from the material to be dried F to the shelf plate 11a (a heat flow path in which convection due to the gas inside the drying chamber 10 is dominant) and the heat medium (a heat flow path in which heat conduction is dominant). Finally, heat is exhausted by a heat extraction source inside the heat medium supply source 13. At the stage where the amount of heat removed exceeds the phase transition temperature to solid phase, the material to be dried F freezes.

Next, under the control of the control unit 40, the internal atmosphere (internal pressure) of the drying chamber 10 is set to a pressure range in which the material to be dried F does not exhibit a collapse phenomenon, and then heat removal is started. At this time, the adjustment unit 12 supplies heat to the medium in the medium flow path 11b in the shelf board 11a, and heats each shelf board 11a of the shelf 11 in the drying chamber 10. Thereby, the material to be dried F placed on the shelf board 11a is heated, and the drying of the material to be dried F is promoted. The ice contained in the heated material to be dried F absorbs latent heat from the material to be dried and sublimes into water vapor. The generation of water vapor causes an increase in internal pressure. However, in this configuration, by opening the gate valve 24 and using the cold trap 23 and vacuum pump 22 inside the collection section 20, the internal pressure of the drying chamber 10 can be evacuated to within the above pressure range. It becomes. Note that the target value of the internal pressure must be a value that does not cause a collapse phenomenon on the sublimation surface. Here, too low pressure (internal pressure) causes a decrease in the molecular weight of the gas interposed between the contact surface between the container 100 and the shelf 11, resulting in a proportional decrease in heat flux (that is, drying is delayed). Therefore, as the target value of the ideal internal pressure, it is preferable to set the maximum pressure that does not cause the collapse phenomenon within the range of the sublimation surface temperature of the material to be dried F, which will be described later. Note that the collapse phenomenon refers to a phenomenon in which the three-dimensional structure of a solute observed after freeze-drying is not uniform. In other words, the collapse phenomenon is a phenomenon in which the sublimation surface does not dry uniformly over time. The collapse phenomenon is a phenomenon that should be avoided from the viewpoint of product quality.

The vacuum pump 22 exhausts the gas containing water vapor in the drying chamber 10 via the collection section 20. Since the vacuum pump 22 is usually configured as a gas transport type vacuum pump, the pumping speed for water vapor is not sufficient. However, the cold trap 23 located within the collection section 20 functions as a gas storage vacuum pump. Therefore, the drying chamber 10 is evacuated by both the vacuum pump 22 and the cold trap 23. As a result, the drying chamber 10 can ensure a predetermined exhaust speed and at the same time maintain a target internal pressure. Note that the vacuum drying process of the material to be dried F in the vacuum drying apparatus 1 as described above is merely an example, and the contents of the process can be changed as appropriate.

The control unit 40 of the vacuum drying apparatus 1 of this embodiment controls the adjustment unit 12 based on the fluid pressure P2 of the fluid in the contraction side piping 37 measured by the contraction side pressure sensor 39 when performing the vacuum drying process. This is used to control the heat flux to the material to be dried F and, in turn, the temperature at the sublimation surface. The control unit 40 controls the adjustment unit 12 based on the measurement result of the contraction side pressure sensor 39, and controls the temperature Ts of the shelf 11. The control unit 40 converts the measurement result of the contraction side pressure sensor 39 into the weight of the shelf 11 supporting the material to be dried F, and controls the adjustment unit 12 based on the weight of the shelf 11.

When the dried material F placed on the shelf 11 in the drying chamber 10 dries, its weight decreases according to the amount of sublimation (mass). When the weight of the dried material F decreases, the total weight of the dried material F and the weight of the shelf 11 on which the dried material F is placed decreases. When the total weight of the items to be dried F and the shelf 11 decreases, the downward force in the direction of gravity that acts from the shelf 11 on the fluid cylinder 30 that supports the shelf 11 in order to raise and lower the shelf 11 decreases. When the downward force in the direction of gravity acting on the fluid cylinder 30 decreases, the fluid pressure P2 in the contraction side pipe 37 changes (increases). The fluid pressure P2 in the contraction side pipe 37 is measured by the contraction side pressure sensor 39, and the measurement result is output to the control section 40. The control section 40 calculates (change in) the weight of the object to be dried F based on the measured value of the fluid pressure P2, and controls the drying conditions of the object to be dried F by the adjustment section 12.

As shown in FIG. 3, the control section 40 functionally includes an input reception section 41, a storage section 42, a weight conversion section 43, a temperature calculation section 44, and a heating temperature control section 45.
The input receiving unit 41 receives from the contraction side pressure sensor 39 a measurement result of the contraction side pressure sensor 39, that is, a signal indicating the fluid pressure P2 of the fluid in the contraction side piping 37. The storage unit 42 stores various setting values and the like necessary for controlling the heating of the material to be dried F in the control unit 12 in the control unit 40 .

The weight conversion unit 43 converts the weight of the shelf 11 based on the fluid pressure P2 received by the input reception unit 41. The weight of shelf 11 is the load supported by fluid cylinder 30. That is, the weight of the shelf 11 is the total weight of the weight of the material to be dried F and the weight of the shelf 11 on which the material to be dried F is placed.

Here, the conversion formula showing the correlation between the fluid pressure P2 measured by the contraction side pressure sensor 39 and the load acting on the fluid cylinder 30 (the weight of the shelf 11) is based on the specifications of the fluid cylinder 30 and experiments conducted in advance. obtained based on. The weight conversion unit 43 converts and obtains the weight of the shelf 11 supported by the fluid cylinder 30, which corresponds to the measurement result of the fluid pressure P2, based on a conversion formula obtained in advance. The purpose of the experiment conducted in advance is to detect the weight variation of the material to be dried F. Therefore, in the example of the experiment, all the objects to be dried F are carried onto the shelf 11, and the shelf 11 and all the objects to be dried F (the entire mass suspended in the initial state) are suspended by the fluid cylinders 30. and record the value of fluid pressure P2 at this point as an initial value. Thereafter, the weight (mass) is removed in a unit according to the desired resolution, and the fluid pressure P2 corresponding to each weight is measured and recorded until the end point (the weight of the dried material F in the final dry state). As a result, a conversion table (or a conversion formula that approximates the table) may be created in advance and stored in the storage unit 42.

The temperature calculation unit 44 calculates the temperature of the material to be dried F, particularly the temperature at the sublimation surface, based on the weight of the shelf 11 converted by the weight conversion unit 43. The method for calculating the temperature of the material to be dried F will be described in detail later.
The heating temperature control section 45 controls the heating operation of the shelf 11 in the adjustment section 12 based on the temperature of the material to be dried F calculated by the temperature calculation section 44 .

Next, a temperature control method in the vacuum drying apparatus 1 in this embodiment will be explained. In the temperature adjustment method in the vacuum drying apparatus 1 in this embodiment, the heat transfer coefficient Kv of the container 100 containing the material to be dried F is determined in advance. This heat transfer coefficient Kv takes a different value depending on the shape, material, and surface condition of the container, so even if the container 100 is called a vial, it needs to be determined each time if the shape etc. is different.
The heat transfer coefficient Kv is expressed by the following formula (1).

Here, ΔH: latent heat of sublimation of the material to be dried F, dm/dt: sublimation water vapor mass (mass flow rate) per unit time (of the entire material to be dried) [kg/h], N: amount of water vapor placed on the shelf 11. The number of containers 100 placed, Av: cross-sectional area per container 100 (vial cross-sectional area) [m ² ], Ts: shelf temperature [K], Tb: bottom center temperature of container 100. Note that Av (cross-sectional area per container 100) means not the internal cross-sectional area of each container 100 but the external cross-sectional area. Further, the container 100 is assumed to have a substantially cylindrical shape (vial shape). However, if the container 100 has a shape other than a vial shape, the area surrounded by the outermost periphery of the contact point (stamp area) where the container 100 contacts the shelf 11 or the projected area of the bottom of the container 100 is taken as the external cross-sectional area. It's fine if you handle it. In other words, the cross-sectional area Av per container 100 is the area of a region where heat exchange through the mean free path based on the internal pressure of the drying chamber 10 is dominant (hereinafter, this region is referred to as a contact area).

The above formula (1) is obtained based on the following formulas (2) and (3), which are basic formulas for heat mass transfer in freeze-drying (note that formula (6), which will be described later, is also one of these basic formulas). ). Equation (2) is based on the fact that heat is conducted to the container 100 by the temperature difference between the shelf temperature Ts and the bottom center temperature Tb of the container 100 as the temperature of the material to be dried F and the contact area (note that the contact area It is assumed that the atmosphere inside and outside the area is within a certain range, including pressure). Equation (3) is based on the fact that the amount of heat used for sublimation and the amount of sublimated water are related by the heat of sublimation of water.

Here, dQ/dt: heat flow rate [J/s].

To determine the heat transfer coefficient Kv of the container 100, place the container 100 containing pure water (ice: ΔH=2800 [J/g]) whose latent heat of sublimation ΔH is known on the shelf 11 of the vacuum drying device 1. A predetermined number will be installed. Among the plurality of containers 100 placed on the shelf 11, the temperature of the material to be dried F (product temperature, bottom center temperature Tb of the container 100) is measured in a container 100 located at the center or end of the shelf 11, for example. Install the product temperature sensor. More specifically, the temperature of the material to be dried F described above is the temperature on the interface side of the bottom surface of the material to be dried F in the center of the container 100. However, in actual measurement, a product temperature sensor is attached to the center of the bottom surface of the container 100, and the temperature measured by the product temperature sensor (temperature at the center of the bottom surface of the container 100) is regarded as the temperature of the material to be dried F. It will be implemented.

After that, the material to be dried F is dried in the drying chamber 10 under the same conditions (number of containers 100, internal pressure (vacuum degree) and temperature of the drying chamber 10) as when actually freeze-drying the material to be dried. 11 is measured, and the amount of sublimated water vapor dm/dt per unit time, that is, the weight change rate due to sublimation of pure water in the container 100 is calculated. At this time, the freeze-drying process may be terminated when the material to be dried F (in this case, pure water) has been sublimated, for example, by about 30 to 80%, and the weights of the plurality of containers 100 may be individually measured. . In this case, it is possible to examine not the average weight of the plurality of containers 100 but the positional dependence of the containers 100 on the shelf 11.
Further, the supply side temperature sensor 19A and the collection side temperature sensor 19B provided in the adjustment section 12 are used to measure the shelf temperature Ts. As the shelf temperature Ts, the average value of the measurement value of the supply side temperature sensor 19A and the measurement value of the collection side temperature sensor 19B can be used. However, the presence of a difference between the measured value of the supply-side temperature sensor 19A and the measured value of the recovery-side temperature sensor 19B indicates that a temperature distribution has occurred, which is inconvenient for the freeze-drying apparatus. In other words, it is desirable to have a design that can secure a sufficient flow rate for the medium, and to have the ability to keep the absolute value of the difference during freeze-drying (during stable operation excluding initial stages, etc.) to less than 1.5°C. In this case, there is no problem in using one of the temperature sensors as a representative value.

Next, in the above equation (1), the calculated value of the sublimated water vapor amount dm/dt, the measured value of the shelf temperature Ts, the measured value of the bottom center temperature Tb of the container 100, and the number of containers 100 placed on the shelf 11 are added. Substitute N and the cross-sectional area Av (known) per container 100. Thereby, the heat transfer coefficient Kv of the container 100 is determined. The determined heat transfer coefficient Kv of the container 100 is stored in the storage unit 42 for use in the freeze-drying process of the material to be dried F, which is a production operation to be described later.

After determining the heat transfer coefficient Kv of the container 100 in this way, when actually freeze-drying the material to be dried F in the vacuum drying device 1, the control unit 40 controls the vacuum drying device as follows. Control the temperature adjustment in 1.

First, as shown in FIG. 4, the control unit 40 receives a signal indicating the measurement result of the fluid pressure P2 from the contraction side pressure sensor 39 at the input reception unit 41 at predetermined time intervals ( Step S1).

When the control unit 40 receives the measurement result of the fluid pressure P2, the weight conversion unit 43 converts the weight of the shelf 11 based on the fluid pressure P2 (step S2). To do this, as described above, the weight of the shelf board 11a supported by the fluid cylinder 30 is converted and obtained from the measurement result of the fluid pressure P2 based on a conversion formula obtained in advance.

Next, the control unit 40 uses the temperature calculation unit 44 to calculate the temperature of the object to be dried F based on the obtained weight of the shelf 11 (step S3). In this embodiment, the temperature calculation unit 44 calculates the latent heat of sublimation ΔH of the material to be dried F, the weight of the shelf 11 (measurement result of the contraction side pressure sensor 39), the cross-sectional area Av of the container 100, and the predetermined heat transfer coefficient Kv. Based on this, the bottom center temperature Tb [K] of the container 100 is calculated as the temperature of the material to be dried F. Note that the value of the latent heat of sublimation ΔH may be determined by using the value of the solvent of the material to be dried F. However, if the value of the latent heat of sublimation ΔH varies significantly depending on the solute, a value obtained by multiplying the value of the solvent by a correction coefficient obtained through experiments in advance may be used.

To calculate the bottom center temperature Tb of the container 100, the following equation (4) obtained based on the above equations (2) and (3) is used.

Here, the average value of the measured value of the supply side temperature sensor 19A and the measured value of the collection side temperature sensor 19B can be used as the shelf temperature Ts. Further, the latent heat of sublimation ΔH of the material to be dried F, the number N of containers 100 placed on the shelf 11, and the cross-sectional area Av per container 100 are known. For the heat transfer coefficient Kv of the container 100, the value determined in advance is used. Substitute these values into the above equation (4).
Further, the sublimated water vapor amount dm/dt per unit time is obtained from the weight of the shelf 11 converted based on the fluid pressure P2. That is, the amount of sublimated water vapor dm/dt can be calculated from the difference in the weight of the shelf 11 at two different times. The sublimated water vapor amount dm/dt is, in other words, the sublimation rate of the material F to be dried.

Furthermore, the thickness L _ice (see FIG. 2) of the frozen layer L2 is calculated from the weight (known) of the material to be dried F stored in the container 100, based on the weight m (amount of sublimation) of the material to be dried that has sublimated. be done. Thereby, the bottom center temperature Tb of the container 100 calculated by the formula (4) can be converted into the temperature T _ice of the sublimation surface Lf of the material to be dried F by the following formula (5). Note that the conditions are that the volume of the solution forming the initial weight m of the material to be dried F when frozen is known, and that the internal shape of the container 100 (usually cylindrical) is known. In other words, before the solvent is sublimated, L _ice has a known thickness in the container 100, and of the weight m of the material to be dried F, all the mass equivalent to the weight of the solvent has sublimated. At this point, the thickness of the _Lice becomes zero. For example, if the internal shape of the container 100 is cylindrical, its cross-sectional area is the same from a known thickness position to zero. Therefore, the amount of sublimation of the solvent, that is, the weight m of the sublimated material to be dried F and the thickness of _Lice have a linear proportional relationship (a relationship expressed by a linear function). Therefore, by using this proportional relationship, it is possible to easily calculate the thickness _Lice of the frozen layer L2 from the obtained weight of the shelf 11.

Here, K _ice is the heat transfer coefficient [J/s·m·K] of the frozen layer L2. This value is stored in the storage unit 42 from the beginning as a known value. This value is obtained from literature or experiments.

In this manner, in step S3, the temperature calculation unit 44 obtains the temperature of the object F to be dried by converting the center temperature Tb of the bottom of the container 100 and the temperature _Tice of the sublimation surface Lf of the object F to be dried. be able to.

The control unit 40 uses a heating temperature control unit 45 to control the heating operation of the shelf 11 in the adjustment unit 12 based on the temperature of the material to be dried F calculated by the temperature calculation unit 44 in step S3 (step S4). . The temperature of the material to be dried F used here may be either the bottom center temperature Tb of the container 100 or the temperature _Tice of the sublimation surface Lf of the material to be dried F.

The specific method of heating the shelf 11 in the adjustment section 12 based on the temperature of the material to be dried F in step S4 is not limited at all. For example, the heating temperature control unit 45 controls heating so that the temperature of the material to be dried F (bottom center temperature Tb of the container 100 or temperature _Tice of the sublimation surface Lf of the material to be dried F) is maintained below the collapse temperature. Preferably, the temperature control section 45 controls the operation of the adjustment section 12. In addition, in order to improve the efficiency of the vacuum drying process, the heating temperature control section 45 adjusts the temperature of the material to be dried so that the temperature of the material to be dried is below the collapse temperature and as high as possible. Preferably, 12 operations are controlled. Note that instead of the collapse temperature of the material to be dried F, the glass transition point, melting point, or eutectic point of the material to be dried, the temperature at which the material is used as a product, etc. may be used as a reference for the temperature. In other words, for example, the temperature may be based on important material properties of drug substances and pharmaceuticals.

As explained above, according to the vacuum drying apparatus 1 according to the present embodiment, the fluid supply and discharge system 35 that supplies and discharges fluid to and from the fluid cylinder 30 that raises and lowers the shelf 11 on which the object to be dried F is placed is provided. A contraction side pressure sensor 39 is provided and measures the fluid pressure P2 of the fluid.
In such a configuration, when the object to be dried F placed on the shelf 11 in the drying chamber 10 dries and its weight decreases, the total weight of the object to be dried F suspended and the shelf 11 decreases. do. Then, the downward force in the direction of gravity that acts from the shelf 11 on the fluid cylinder 30 that supports the shelf 11 in order to raise and lower the shelf 11 is also reduced. As a result, the fluid pressure P2 within the fluid cylinder 30 changes. Since the contraction side pressure sensor 39 measures the fluid pressure P2 supplied to and discharged from the fluid cylinder 30, based on the change in the measurement result in the contraction side pressure sensor 39, the weight reduction due to drying of the dried material F is determined. can be detected. The change in weight of the object to be dried F due to drying and the change in the fluid pressure P2 of the fluid cylinder 30 are directly correlated. Therefore, it becomes possible to detect the drying state of the material to be dried F more directly and to grasp the drying state of the material to be dried F with higher precision.

The vacuum drying apparatus 1 further includes an adjustment section 12 that adjusts the temperature Ts of the shelf 11, and a control section 40 that controls the adjustment section 12 based on the measurement result of the contraction side pressure sensor 39.
With such a configuration, it is possible to grasp the change in weight of the object to be dried F due to drying based on the measurement result of the contraction side pressure sensor 39, that is, the change in the fluid pressure P2 of the fluid cylinder 30. As a result, the control unit 40 adjusts the temperature Ts of the shelf 11 in the adjustment unit 12 based on the change in the fluid pressure P2 of the fluid cylinder 30, so that the drying target F The temperature Ts of the shelf 11 for drying can be appropriately adjusted.

Further, the control unit 40 converts the measurement result of the contraction side pressure sensor 39 into the weight of the shelf 11 that supports the material to be dried F, and controls the adjustment unit 12 based on the weight of the shelf 11.
In such a configuration, the weight of the shelf 11 is known. Therefore, by converting the total weight of the weight of the dried material F and the weight of the shelf 11 from the measurement result of the fluid pressure P2 of the fluid cylinder 30, which is the measurement result of the contraction side pressure sensor 39, Changes in the drying state of object F can be grasped. Therefore, the temperature Ts of the shelf 11 can be appropriately adjusted depending on the drying state of the material to be dried F.

Further, the control unit 40 controls the temperature of the shelf 11 based on the latent heat of sublimation ΔH of the material to be dried F, the weight of the shelf 11 (measurement result of the contraction side pressure sensor 39), the cross-sectional area Av of the container 100, and the heat transfer coefficient Kv. Adjust temperature Ts.
In such a configuration, the temperature of the material to be dried F (bottom center temperature Tb of the container 100 , the temperature T _ice ) of the sublimation surface Lf of the material to be dried F can be calculated. Thereby, by adjusting the temperature Ts of the shelf 11 according to the temperature state of the material to be dried F, it is possible to dry the material to be dried F under appropriate conditions.

Further, the control unit 40 controls the adjustment unit 12 based on the measurement result of the contraction side pressure sensor 39 so that the temperature of the material to be dried F becomes equal to or lower than the collapse temperature.
If the temperature of the material to be dried exceeds the collapse temperature even in only a part of the region, a collapse phenomenon occurs in which the portion of the material to be dried where the moisture is frozen shrinks, and the material to be dried will not be properly dried. and the quality deteriorates. In the configuration of this embodiment, the temperature Ts of the shelf 11 is appropriately adjusted based on the change in the fluid pressure P2 of the fluid cylinder 30, so that the temperature of the material to be dried F, especially the sublimation surface temperature, is below the collapse temperature. By maintaining this, the material to be dried F can be dried satisfactorily.

According to the method for adjusting the temperature of the shelf 11 in the vacuum drying apparatus 1 according to the present embodiment, based on the fluid pressure P2 of the fluid in the fluid supply and discharge system 35 that supplies and discharges fluid to and from the fluid cylinder 30 that raises and lowers the shelf 11. , adjust the temperature Ts of the shelf 11.
In such a configuration, when the object to be dried F placed on the shelf 11 in the drying chamber 10 dries and its weight decreases, the total weight of the object to be dried F and the shelf 11 decreases. Then, the downward force in the direction of gravity that acts from the shelf 11 on the fluid cylinder 30 that supports the shelf 11 in order to raise and lower the shelf 11 is reduced. This causes the fluid pressure within the fluid cylinder 30 to change. Since the contraction side pressure sensor 39 measures the fluid pressure P2 supplied to and discharged from the fluid cylinder 30, based on the change in the measurement result in the contraction side pressure sensor 39, the weight reduction due to drying of the dried material F is determined. can be detected. The change in weight of the object to be dried F due to drying and the change in the fluid pressure P2 of the fluid cylinder 30 are directly correlated. Therefore, it becomes possible to detect the drying state of the material to be dried F more directly and to grasp the drying state of the material to be dried F with higher precision.

Furthermore, according to the method of adjusting the temperature of the shelf 11 in the vacuum drying apparatus 1, the fluid pressure P2 is converted into the weight of the shelf 11 supporting the material to be dried F, and the temperature Ts of the shelf 11 is determined based on the weight of the shelf 11. Control.
In such a configuration, since the dead weight of the shelf 11 is known, and the dead weight attached to the dried material F can also be known, the weight of the shelf 11 supporting the dried material F can be determined from the fluid pressure P2 of the fluid cylinder 30. By converting and determining the weight, that is, the total weight of the material to be dried F and the shelf 11, changes in the drying state of the material to be dried F can be grasped. Therefore, the temperature Ts of the shelf 11 can be appropriately adjusted depending on the drying state of the material to be dried F.

According to the method for adjusting the temperature of the shelf 11 in the vacuum drying apparatus 1 according to the present embodiment, the temperature Ts of the shelf 11 is adjusted based on the weight of the shelf 11 supporting the material to be dried F.
In such a configuration, when the object to be dried F placed on the shelf 11 in the drying chamber 10 is dried, the total weight of the object to be dried F and the shelf 11 on which the object to be dried F is placed is reduced. Thereby, the drying state of the object to be dried F can be grasped from the weight of the shelf 11 that supports the object to be dried. Therefore, the drying state of the material to be dried F can be detected more directly than, for example, a method that measures the amount of sublimated water vapor, so it is possible to grasp the drying state of the material to be dried F with higher precision. becomes.

Further, according to the method of adjusting the temperature of the shelf 11 in the vacuum drying apparatus 1 according to the present embodiment, the material to be dried F is placed on the shelf 11 while being housed in the container 100, and the material to be dried F is sublimated. The temperature Ts of the shelf 11 is adjusted based on the latent heat ΔH, the weight of the shelf 11 (measured by the contraction side pressure sensor 39), the cross-sectional area Av of the container 100, and the heat transfer coefficient Kv.
In such a configuration, the weight of the material to be dried F is calculated based on the weight of the shelf 11, the latent heat of sublimation ΔH of the material to be dried F, the measurement result of the contraction side pressure sensor 39, the cross-sectional area Av of the container 100, and the heat transfer coefficient Kv. It can be determined by calculating the temperature. Thereby, by adjusting the temperature Ts of the shelf 11 according to the temperature state of the material to be dried F, it is possible to dry the material to be dried F under appropriate conditions.

Furthermore, according to the method of adjusting the temperature of the shelf 11 in the vacuum drying apparatus 1 according to the present embodiment, the temperature Ts of the shelf 11 is adjusted based on the weight of the shelf 11 so that the temperature of the material to be dried F becomes below the collapse temperature. Control.
In such a configuration, when the temperature of the material to be dried F exceeds the collapse temperature, a collapse phenomenon occurs in which the portion of the material to be dried F where the water is frozen contracts, and the material to be dried is not properly dried. It disappears. The temperature Ts of the shelf 11 is appropriately adjusted based on the change in the fluid pressure P2 of the fluid cylinder 30, and the temperature of the dried material F is maintained so as to be below the collapse temperature, thereby drying the dried material F. It can be done well.

(Modified example of embodiment)
In the above embodiment, in step S3, when calculating the temperature of the material to be dried F based on the weight of the shelf 11, the temperature calculation unit 44 calculates the latent heat of sublimation ΔH of the material to be dried F, the weight of the shelf 11 (on the shrinkage side Although the temperature of the material to be dried F is calculated based on the measurement result of the pressure sensor 39), the cross-sectional area Av of the container 100, and the heat transfer coefficient Kv, the present invention is not limited thereto.

For example, in step S3, in order to calculate the temperature of the material to be dried F based on the weight of the shelf 11, the internal pressure of the drying chamber 10, the water vapor transfer resistance Rp of the material to be dried F, the product per bottle in the container 100, The temperature Ts of the shelf 11 may be adjusted based on the cross-sectional area Ap and the weight of the shelf 11. Note that Ap (product cross-sectional area per container 100) means the internal cross-sectional area of each container 100, unlike Av.

In the temperature adjustment method in the vacuum drying apparatus 1 in this modification, the water vapor transfer resistance Rp of the dried layer L1 (see FIG. 2) of the material to be dried F is determined in advance.
In order to obtain the water vapor transfer resistance Rp, a predetermined number of objects to be dried F, which are actually objects to be vacuum-dried, are placed in a container 100 and placed on the shelf 11 of the vacuum drying apparatus 1. A product temperature sensor is attached to the container 100 to measure the temperature of the material to be dried F (bottom center temperature Tb of the container 100).

Thereafter, the material to be dried F is dried in the drying chamber 10 under the same conditions (internal pressure (degree of vacuum) and temperature of the drying chamber 10) as when actually freeze-drying, and the weight of the shelf 11 before and after drying is The sublimated water vapor amount dm/dt per unit time is calculated. At this time, the freeze-drying process may be terminated when the material to be dried F has been sublimated, for example, by about 30 to 50%, and the weights of the plurality of containers 100 may be individually measured. In this case, it is possible to examine not the average weight of the containers 100 but the position dependence of the containers 100 on the shelf 11.

Next, the water vapor movement resistance Rp is calculated using equation (7) obtained by modifying equation (6) below.

Here, Ap: product cross-sectional area per container 100 [ ^m2 ], _Pice : sublimation surface pressure [Pa], _PDC : internal pressure of drying chamber [Pa], Rp: water vapor transfer resistance [Pa・m ^2.s /g]. In FIG. 2, the sublimation surface pressure P _ice refers to the dried layer L1 that is generated in the upper layer of the dried material F in the container 100 due to sublimation of water, and the layer that is still frozen below the dried layer L1. This is the pressure that acts on the sublimation surface Lf formed at the boundary between the frozen layer L2 and the sublimation surface Lf. The above equation (6) is based on the fact that water sublimates due to the differential pressure between the sublimation surface pressure P _ice and the internal pressure P _DC of the drying chamber (Equation (6) is one of the basic equations for heat mass transfer in freeze-drying. be).

Substitute the calculated value of the sublimated water vapor amount dm/dt, the product cross-sectional area Ap per bottle in the container 100, the sublimation surface pressure P _ice of the material to be dried F, and the internal pressure P _DC of the drying chamber into equation (7). . Thereby, the water vapor transfer resistance Rp is determined. In fact, as shown in equation (7), the sublimation surface pressure P _ice can be expressed by the temperature T _ice of the sublimation surface Lf of the material to be dried F. The temperature T _ice can be determined from the bottom center temperature Tb of the container 100, for example, based on the above equation (5).

Since the water vapor movement resistance Rp differs depending on the material of the material to be dried F, it is preferable to calculate the water vapor movement resistance Rp for each material in the same manner as described above. Furthermore, since the water vapor transfer resistance Rp is dependent on the thickness of the dried layer L1, it is preferable to calculate the water vapor transfer resistance Rp in the same manner as described above by varying the thickness of the dried layer L1 in a plurality of steps. Furthermore, a function showing the correlation between the thickness of the dried layer L1 and the water vapor transfer resistance Rp may be set, and based on this function, the water vapor transfer resistance Rp depending on the thickness of the dried layer L1 may be determined. good. For example, such a function is
Rp=Rp'x(L _max - L _ice )
There is something like. Here, L _max is the maximum (initial) thickness of the frozen layer L2, and L _ice is the thickness of the frozen layer L2.
Further, when the container 100 is closed with a stopper (for example, a rubber stopper) as in this embodiment, the water vapor movement resistance Rp is the sum of the water vapor movement resistance for the dried layer and the water vapor movement resistance of the stopper.

After determining the water vapor transfer resistance Rp in this way, the freeze-drying process of the material to be dried F is actually performed in the vacuum drying apparatus 1.
As shown in FIG. 4, similarly to the above embodiment, the control section 40 sends a signal indicating the measurement result of the fluid pressure P2 at the contraction side pressure sensor 39 at the input reception section 41 at predetermined time intervals. (Step S1).
When the control unit 40 receives the measurement result of the fluid pressure P2, the weight conversion unit 43 converts the weight of the shelf 11 based on the fluid pressure P2 (step S2).

Next, the control unit 40 uses the temperature calculation unit 44 to calculate the temperature of the object to be dried F based on the obtained weight of the shelf 11 (step S3). In this modification, the temperature calculation unit 44 of the control unit 40 calculates the internal pressure P _DC of the drying chamber 10 , the water vapor transfer resistance Rp of the material to be dried F determined above, the number N of containers 100 , and the Based on the product cross-sectional area Ap and the amount of sublimated water vapor per unit time dm/dt calculated from the weight of the shelf 11 converted in step S2, the temperature of the material to be dried F is determined by the following formula (8). The temperature T _ice of the sublimation surface Lf is calculated.

Furthermore, based on the above equation (5), the temperature _Tice of the sublimation surface Lf of the material to be dried F can be converted into the bottom center temperature Tb of the container 100, and this can be taken as the temperature of the material to be dried F.
In this way, as the temperature of the material to be dried F, the temperature T _ice of the sublimation surface Lf of the material to be dried F or the bottom center temperature Tb of the container 100 is obtained.

After that, in step S4, the heating temperature control unit 45 heats the shelf 11 in the adjustment unit 12 based on the temperature of the dried material F calculated by the temperature calculation unit 44 in step S3, as in the above embodiment. Control behavior.

According to the vacuum drying device 1 and the temperature adjustment method of the shelf 11 in the vacuum drying device 1 of this modification, the material to be dried F is placed on the shelf 11 while being accommodated in the container 100, and the control unit 40 adjusts the temperature Ts of the shelf 11 based on the internal pressure of the drying chamber 10, the water vapor transfer resistance Rp of the material to be dried F, the cross-sectional area Ap of each product in the container 100, and the weight of the shelf 11.
In such a configuration, the temperature of the material to be dried F is determined based on the internal pressure of the drying chamber 10, the water vapor transfer resistance Rp for the material to be dried, the cross-sectional area Ap of each product in the container 100, and the weight of the shelf 11. It can be calculated and found. Therefore, by adjusting the temperature Ts of the shelf 11 according to the temperature state of the material to be dried F, the material to be dried F can be dried under appropriate conditions.

Note that the technical scope of the present invention is not limited to the embodiments described above, and various changes can be made without departing from the spirit of the present invention.

For example, in the above embodiment, the fluid pressure P2 in the contraction side pipe 37 is measured by the contraction side pressure sensor 39 in order to convert and obtain the weight of the shelf 11, but the present invention is not limited to this. The expansion side pressure sensor 38 may measure the fluid pressure in the contraction side piping 37, or the expansion side pressure sensor 38 may measure the fluid pressure P2 in the contraction side piping 37 measured by the contraction side pressure sensor 39. The weight of the shelf 11 may be converted and obtained based on the differential pressure between the measured fluid pressure in the extension pipe 36 and the measured fluid pressure in the extension pipe 36 .

In the embodiment described above, the temperature of the material to be dried F (the bottom center temperature Tb of the container 100 or the temperature of the material to be dried F Although the adjustment unit 12 is controlled by obtaining the temperature T _ice ) of the sublimation surface Lf, the present invention is not limited thereto. The adjustment unit 12 may be controlled based on the fluid pressure P2 in the contraction side piping 37 measured by the contraction side pressure sensor 39, using the sublimation surface pressure Pice of the material to be dried F as a key.

In addition, without departing from the spirit of the present invention, the components in the embodiments described above may be replaced with well-known components as appropriate, and the above-described modifications may be combined as appropriate.

1 Vacuum drying device 10 Drying chamber 11 Shelf 12 Adjustment section 20 Collection section 30 Fluid cylinder 35 Fluid supply/discharge system 39 Contraction side pressure sensor (measuring section)
40 Control unit 100 Vial F Material to be dried △H Latent heat of sublimation Kv Heat transfer coefficient L1 Dry layer P2 Fluid pressure Rp Water vapor transfer resistance Tice Temperature Ts Temperature

Claims (10)

a drying room,
a shelf arranged in the drying chamber and on which items to be dried are placed;
a fluid cylinder that raises and lowers the shelf;
a fluid supply and discharge system that supplies and discharges fluid to and from the fluid cylinder;
a measurement unit that is provided in the fluid supply and drainage system and measures the fluid pressure of the fluid;
a collection unit that collects moisture sublimed from the material to be dried;
an adjustment unit that adjusts the temperature of the shelf;
A vacuum drying apparatus comprising : a control section that controls the adjustment section based on the measurement result of the measurement section . The control unit includes:
At each of two different times, converting the measurement results of the measurement unit into the weight of the shelf supporting the drying material,
Calculating the sublimation rate of the dried material from the differences between these two times and weights,
Calculating the estimated temperature of the material to be dried based on the sublimation rate,
The vacuum drying apparatus according to claim 1 , wherein the adjustment section is controlled so that the estimated temperature is equal to or lower than a preset threshold. The item to be dried is placed on the shelf while being housed in a container,
The vacuum drying apparatus according to claim 2 , wherein the control unit calculates the estimated temperature based on the latent heat of sublimation of the material to be dried, the sublimation rate, the cross-sectional area of the container, and the heat transfer coefficient of the container. The item to be dried is placed on the shelf while being housed in a container,
The vacuum drying according to claim 2 , wherein the control unit calculates the estimated temperature based on the internal pressure of the drying chamber, the water vapor transfer resistance of the object to be dried, the cross-sectional area of the product in the container, and the sublimation rate. Device. The vacuum drying apparatus according to any one of claims 2 to 4 , wherein the threshold value is a collapse temperature. a drying room,
a shelf arranged in the drying chamber and on which items to be dried are placed;
a fluid cylinder that raises and lowers the shelf;
A method for adjusting the temperature of the shelf in a vacuum drying apparatus including a collection unit that collects moisture sublimed from the object to be dried, the method comprising:
A method for adjusting the temperature of a shelf in a vacuum drying apparatus, wherein the temperature of the shelf is adjusted based on the fluid pressure of the fluid in a fluid supply and discharge system that supplies and discharges fluid to and from the fluid cylinder. At each of two different times, converting the fluid pressure into the weight of the shelf supporting the object to be dried,
Calculating the sublimation rate of the dried material from the differences between these two times and weights,
Calculating the estimated temperature of the material to be dried based on the sublimation rate,
The method for adjusting the temperature of a shelf in a vacuum drying apparatus according to claim 6 , wherein the temperature of the shelf is controlled so that the estimated temperature is equal to or lower than a preset threshold. The item to be dried is placed on the shelf while being housed in a container,
8. The method for adjusting the temperature of a shelf in a vacuum drying apparatus according to claim 7 , wherein the estimated temperature is calculated based on the latent heat of sublimation of the material to be dried, the sublimation rate, the cross-sectional area of the container, and the heat transfer coefficient of the container. The item to be dried is placed on the shelf while being housed in a container,
The temperature of the shelf in the vacuum drying apparatus according to claim 7 , wherein the estimated temperature is calculated based on the internal pressure of the drying chamber, the water vapor transfer resistance of the material to be dried, the cross-sectional area of the product in the container, and the sublimation rate. Adjustment method. The method for adjusting the temperature of a shelf in a vacuum drying apparatus according to any one of claims 7 to 9 , wherein the threshold value is a collapse temperature.

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