JP2021092327A - Vacuum dryer, and method of controlling temperature of shelf in vacuum dryer - Google Patents

Abstract

To provide a vacuum dryer capable of more directly detecting the drying condition of drying objects and of more accurately recognizing the drying condition of the drying objects, and a method of controlling the temperature of a shelf in the vacuum dryer.SOLUTION: There is provided a vacuum dryer 1 comprising: a drying chamber 10; a set of shelves 11, which is disposed in the drying chamber 10, and on which drying objects F are placed; a fluid cylinder 30 that lifts the shelf 11; a fluid feeding/discharging system 35 that feeds/discharges a fluid to/from the fluid cylinder 30; a measurement section 39 provided in the fluid feeding/discharging system 35 to measure a fluid pressure P2 of the fluid; and a capturing section 20 that captures moisture subliming from the drying objects F.SELECTED DRAWING: Figure 1

Description

The present invention relates to a vacuum dryer and a method for controlling the temperature of shelves in a vacuum dryer.

Conventionally, freeze-drying condition monitoring devices such as those described in Patent Document 1 below have been known.

JP-A-2015-31486

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

The present invention has been made in view of the above circumstances, and an object of the present invention is to grasp the dry state of the object to be dried, particularly the sublimation surface temperature, with higher accuracy.

In order to solve the above problems, the present invention proposes the following means.
The vacuum drying apparatus according to the present invention supplies and discharges fluid to a drying chamber, a shelf on which an object to be dried is placed, a fluid cylinder for raising and lowering the shelf, and the fluid cylinder. It is provided with a fluid supply / discharge system, a measurement unit provided in the fluid supply / discharge system for measuring the fluid pressure of the fluid, and a collection unit for collecting water sublimated from the object to be dried.

In the present invention, when the object to be dried placed on the shelf in the drying chamber dries, its weight decreases. As the weight of the object to be dried decreases, the total weight of the object to be dried and the shelf on which the object to be dried is placed also decreases. As the total weight of the object to be dried and the shelves decreases, so does the downward force in the direction of gravity acting on the fluid cylinders that support the shelves to raise and lower the shelves. As a result, the fluid pressure in the fluid cylinder changes. Since the measuring unit measures the fluid pressure supplied to and discharged from the fluid cylinder, it is possible to detect a decrease in weight due to drying of the object to be dried based on the change in the measurement result in the measuring unit. The change in weight due to drying of the object to be dried and the change in fluid pressure of the fluid cylinder are directly correlated. Therefore, it is possible to directly detect the dry state of the object to be dried and grasp the dry state of the object to be dried with higher accuracy.

Further, an adjusting unit for adjusting the temperature of the shelf and a control unit for controlling the adjusting unit based on the measurement result of the measuring unit may be further provided.

In this case, it is possible to grasp the change in weight due to the drying of the object to be dried based on the measurement result of the measuring unit, that is, the change in the fluid pressure of the fluid cylinder. 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 object to be dried is adjusted according to the drying state of the object to be dried. Can be adjusted appropriately.

Further, the control unit converts the measurement result of the measurement unit into the weight of the shelf supporting the object to be dried at each of the two different times, and the difference between the two times and the weight indicates the subject. The sublimation rate of the dried product is calculated, the estimated temperature of the object to be dried is calculated based on the sublimation speed, and the adjusting unit is controlled so that the estimated temperature is equal to or lower than a preset threshold value. May be good.

In this case, the weight of the shelf is known. Therefore, from the measurement result of the fluid pressure of the fluid cylinder, which is the measurement result of the measuring unit, the weight of the shelf supporting the object to be dried, that is, the total weight of the weight of the object to be dried and the weight of the shelf itself is converted and obtained. Therefore, the change in the dry state of the object to be dried can be grasped as the sublimation rate. Then, the temperature of the object to be dried can be estimated from this sublimation rate. Therefore, the temperature of the shelf can be appropriately adjusted according to the dry state of the object to be dried.

Further, the object to be dried is placed on the shelf in a state of being contained in the container, and the control unit receives the latent heat of sublimation of the object to be dried, the sublimation rate, the cross-sectional area of the container, and the transfer of the container. The estimated temperature may be calculated based on the heat coefficient.
Examples of the container include vials, trays, syringes, ampoules and the like.

In this case, the temperature of the object to be dried is estimated with high accuracy by calculating the estimated temperature of the object to be dried based on the sublimation latent heat of the object to be dried, the sublimation rate, the cross-sectional area of the container, and the heat transfer coefficient of the container. be able to. As a result, the temperature of the shelf can be accurately adjusted according to the temperature state of the object to be dried, and the object to be dried can be dried under appropriate conditions.

Further, the object to be dried is placed on the shelf in a state of being contained in the container, and the control unit uses the internal pressure of the drying chamber, the resistance of water vapor transfer to the object 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 object to be dried is highly accurate by calculating the estimated temperature of the object to be dried 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. Can be estimated to. Therefore, the temperature of the shelf can be accurately adjusted according to the temperature state of the object to be dried, and the object to be dried can be dried under appropriate conditions.

Further, the threshold value may be the collapse temperature.

In this case, when the temperature of the object to be dried exceeds the collapse temperature, a collapse phenomenon occurs in which the portion where the moisture of the object to be dried is frozen shrinks, and the object to be dried cannot be dried well. By appropriately adjusting the temperature of the shelf based on the change in the fluid pressure of the fluid cylinder and keeping the temperature of the object to be dried below the collapse temperature, the object to be dried can be dried well. ..

The method for controlling the temperature of a shelf in the vacuum drying apparatus according to the present invention is a drying chamber, a shelf arranged in the drying chamber on which an object to be dried is placed, a fluid cylinder for raising and lowering the shelf, and the object to be dried. A method of adjusting the temperature of the shelf in a vacuum drying device including a collecting unit for collecting water sublimated from the above, wherein the fluid in a fluid supply / discharge system for supplying / discharging a fluid to the fluid cylinder. The temperature of the shelf is adjusted based on the fluid pressure of.

In the present invention, when the object to be dried placed on the shelf in the drying chamber dries, its weight decreases. As the weight of the object to be dried decreases, the total weight of the object to be dried and the shelf on which the object to be dried is placed also decreases. As the total weight of the object to be dried and the shelves decreases, so does the downward force in the direction of gravity acting on the fluid cylinders that support the shelves to raise and lower the shelves. As a result, the fluid pressure in the fluid cylinder changes. Therefore, based on the fluid pressure of the fluid in the fluid supply / discharge system that supplies the fluid to the fluid cylinder, it is possible to grasp the decrease in weight due to the drying of the object to be dried. The change in weight due to drying of the object to be dried and the change in fluid pressure of the fluid cylinder are directly correlated. Therefore, it is possible to more directly detect the dry state of the object to be dried and to grasp the dry state of the object to be dried with higher accuracy.

Further, at each of the 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 the weight. The estimated temperature of the object 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 value.

In this case, since the self-weight of the shelf is known, the weight of the shelf supporting the object to be dried, that is, the total weight of the object to be dried and the shelf, is determined from the fluid pressure of the fluid in the fluid supply / discharge system that supplies the fluid to the fluid cylinder. By converting and obtaining, the change in the dry state of the object to be dried can be grasped as the sublimation rate. Then, the temperature of the object to be dried can be estimated from this sublimation rate. Therefore, the temperature of the shelf can be appropriately adjusted according to the dry state of the object to be dried.

The method for controlling the temperature of a shelf in the vacuum drying apparatus according to the present invention is 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 sublimated from the object to be dried. A method of adjusting the temperature of the shelf in a vacuum dryer including a collecting unit, wherein the weight of the shelf supporting the object to be dried is measured at two different times, and these two 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 so that the estimated temperature is equal to or less than a preset threshold value. Adjust the temperature of the shelf.

In the present invention, when the object to be dried placed on the shelf in the drying chamber dries, its weight decreases. As the weight of the object to be dried decreases, the total weight of the object to be dried and the shelf on which the object to be dried is placed also decreases. Thereby, the dry state of the object to be dried can be grasped as the sublimation rate from the weight of the shelf supporting the object to be dried. Then, the temperature of the object to be dried can be estimated from this sublimation rate. Therefore, it is possible to more directly detect the dry state of the object to be dried and to grasp the dry state of the object to be dried with higher accuracy.

Further, the object to be dried is placed on the shelf in a state of being contained in the container, and is based on the latent heat of sublimation of the object 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 product is estimated with high accuracy by calculating the estimated temperature of the product to be dried based on the sublimation latent heat of the product to be dried, the sublimation speed, the cross-sectional area of the container, and the heat transfer coefficient of the container. Can be done. As a result, the temperature of the shelf can be accurately adjusted according to the temperature state of the object to be dried, and the object to be dried can be dried under appropriate conditions.

Further, the object to be dried is placed on the shelf in a state of being contained in the container, and 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. The estimated temperature may be calculated based on the above.

In this case, the temperature of the object to be dried is highly accurate by calculating the estimated temperature of the object to be dried 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. Can be estimated to. Therefore, the temperature of the shelf can be accurately adjusted according to the temperature state of the object to be dried, and the object to be dried can be dried under appropriate conditions.

Further, the threshold value may be the collapse temperature.

In this case, when the temperature of the object to be dried exceeds the collapse temperature, a collapse phenomenon occurs in which the portion where the moisture of the object to be dried is frozen shrinks, and the object to be dried cannot be dried well. By appropriately adjusting the temperature of the shelf based on the change in the fluid pressure of the fluid cylinder and keeping the temperature of the object to be dried below the collapse temperature, the object to be dried can be dried well. ..

According to the present invention, the dry state of the object to be dried can be detected more directly, and in particular, the sublimation surface temperature indicating the dry state of the object to be dried can be grasped with higher accuracy.

It is a figure which shows the schematic structure of the vacuum drying apparatus which concerns on one Embodiment of this invention. It is sectional drawing which shows the container which is placed on the shelf of the vacuum drying apparatus shown in FIG. 1 and holds the object to be dried. It is a block diagram which shows the functional structure of the control part of the vacuum drying apparatus which concerns on one Embodiment of this invention. It is a flowchart which shows the flow of the temperature control method of the shelf in the vacuum drying apparatus which concerns on one Embodiment of this invention.

Hereinafter, with reference to the drawings, a vacuum drying device according to an embodiment of the present invention and a method for controlling the temperature of shelves in the vacuum drying device will be described.
The vacuum drying device 1 shown in FIG. 1 is for freezing and vacuum drying the raw material liquid in order to produce, for example, a pharmaceutical product, a pharmaceutical preparation, and a raw material thereof. The raw material liquid is contained in a container 100 as an object to be dried F and is in a solid state (usually in the form of a lump, and in other forms, in the form of sponge or powder) frozen in the previous step. The vacuum drying device 1 mainly includes a drying chamber 10, a collecting unit 20, and a control unit 40. In this example, the container 100 is illustrated as a vial shape and will be described later, but the container form such as a tray, a syringe, and an ampoule can be changed according to the purpose of production.

The drying chamber 10 is a space for vacuum-drying the object to be dried F. The room temperature and internal pressure (vacuum degree) of the drying chamber 10 are adjusted. The degree of vacuum in the drying chamber 10 can be adjusted in the range of, for example, 5 to 300 [Pa]. The temperature and the degree of vacuum (internal pressure) in the drying chamber 10 are measured by sensors (not shown), respectively. The sensor sends the measurement result to the control unit 40 and gives 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 target internal pressure.
A shelf 11 on which the object to be dried F is placed is provided in the drying chamber 10. The shelf 11 includes a plurality of shelf boards 11a spaced apart from each other in the vertical direction. A plurality of containers 100 containing the object to be dried F are placed on each shelf plate 11a.

The shelf 11 is provided with an adjusting unit 12 for adjusting the temperature thereof. The adjusting unit 12 adjusts the heating temperature of the object to be dried F placed on the shelf board 11a by circulating the medium through, for example, the medium flow path 11b provided inside the shelf board 11a. As the heat medium, oil containing silicone as a main component is usually used. As the heat medium, a material having a temperature range of −80 ° C. to + 150 ° C. is generally used. Further, if the performance below the freezing point is unquestioned, such as when it is not necessary to use the medium for the purpose of freezing in the previous step, a medium containing water as a main component is used as the heat medium. As a matter of course, if an inhibitor is added, a medium containing water as a main component can be used under the condition of antifreeze.

The adjusting unit 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 unit 18. There is. The heat medium supply source 13 is a so-called chiller (heat medium circulation device). The heat medium supply source 13 has (1) a heat source such as a heater (not shown) for heating the heat medium, or (2) a heat source and a heat removal source inside. The 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 plate 11a via the supply side header 15 and the supply side branch pipe 15s. The heat medium supplied to the medium flow path 11b heats the object to be dried F housed in the container 100 placed on the shelf plate 11a. The heat medium that has passed through the medium flow path 11b is recovered by the heat medium recovery unit 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 tube 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. The supply-side temperature sensor 19A and the recovery-side temperature sensor 19B may substitute sensors for the same purpose built in the heat medium supply source 13.

The operation of supplying the heat medium in the adjusting unit 12 is controlled by the control unit 40. Specifically, the control unit 40 controls the operation of a heater (not shown) for heating the heat medium and the operation of the supply pump for delivering the heat medium at the heat medium supply source 13. 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 measured value of the supply side temperature sensor 19A and the measured value of the recovery side temperature sensor 19B. Further, the control unit 40 controls the supply operation of the heat medium in the adjustment unit 12 based on the temperature of the object to be dried F, as will be described in detail later. The temperature and flow rate of the series of heat media may be controlled by a control unit (not shown) built in the heat medium supply source 13, and the control unit 40 may give only the target temperature value to the heat medium supply source 13.

Here, as shown in FIG. 2, the container 100 containing the object to be dried F has a bottomed shape having an opening 101 that opens upward. A predetermined amount of the object F to be dried is housed inside the container 100 in the previous step of the vacuum drying device 1. A stopper (not shown) is set in advance in the opening 101 of the container 100. In the opened state in which the stopper (not shown) is set in the opening 101, the inside of the container 100 communicates with the outside, and the water (water vapor) sublimated from the object to be dried F flows out to the outside of the container 100. As will be described later, the shelf plate moving mechanism separates (closes) the atmosphere of the stopper with the opening 101 as a boundary. Therefore, the relative position of the stopper with respect to the container 100 is a position where the atmosphere can be separated by closing the stopper and water can flow out when the stopper is opened.

As shown in FIG. 1, the shelf 11 has the following mechanism for closing the opening 101 of the container 100 with a stopper (not shown) after vacuum drying the object F to be dried in the container 100. ..
The plurality of shelf boards 11a of the shelves 11 can be raised and lowered in the vertical direction by a shelf board moving mechanism (not shown), and the distance between the shelf boards 11a located above and below each other can be increased or decreased. A fluid cylinder 30 is provided on the upper part of the shelf 11 for raising and lowering the plurality of shelf plates 11a to increase or decrease the interval between them.

The fluid cylinder 30 expands and contracts in the vertical direction by the fluid pressure of hydraulic oil, working air, and the like. It should be noted that the fluid is incompressible for the reasons described below, which produces desirable results. Therefore, it is desirable to select a fluid with high incompressibility (for example, oil or water) as the fluid. In the present 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 expands and contracts downward with respect to the cylinder body 31. The extension side oil chamber 31a and the contraction side oil chamber 31b are formed in the cylinder body 31 by being partitioned by a piston 32p provided at the base end portion of the rod 32.

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

When the fluid is supplied from the fluid supply source 33 to the extension side oil chamber 31a in the cylinder body 31 through the extension side pipe 36, the piston 32p is pressed downward in the cylinder body 31. As a result, the rod 32 projects downward from the cylinder body 31, and the fluid cylinder 30 extends downward. With the downward projecting operation of the rod 32, 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 pipe 37.

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

The operation of the fluid supply source 33 of the fluid cylinder 30 is controlled by the control unit 40. Therefore, the extension side pipe 36 is provided with an extension side pressure sensor 38 for measuring the fluid pressure P1 of the fluid in the extension side pipe 36. The contraction side pipe 37 is provided with a contraction side pressure sensor 39 (measurement unit) for measuring the fluid pressure P2 of the fluid in the contraction side pipe 37. By the way, to explain the time-series transition of the fluid pressure during the expansion and contraction operation of the fluid cylinder 30, in the configuration of the present application, the fluid pressure P2 ideally does not fluctuate both during expansion and contraction. The reason for this is that the fluid pressure P1 does not act on the fluid pressure P2 except for the gravity of the structure in which the fluid cylinder 30 is suspended (the fluid pressure P1 at this ideal time is set to zero). Actually, the fluid pressure P2 is affected 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 to the fluid pressure P2. However, components other than the fluid pressure P1 can be ignored at the time of stopping or minute movement. Therefore, the fluid pressure P2 can be treated as being equal to the gravity of the component suspended by the fluid cylinder 30.

When the fluid cylinder 30 is extended under the control of the control unit 40, all the other shelf boards 11a other than the lowermost shelf board 11a among the plurality of shelf boards 11a are moved further downward and are positioned above and below each other. The space between the shelf boards 11a is reduced. 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 a shelf located above. After contact with the lower surface of the plate 11a, it is pressed downward. Hereinafter, this process is referred to as a pressing operation to distinguish it from an expansion / contraction operation. As a result, a stopper (not shown) is pushed into the opening 101 of the container 100, and the opening 101 is closed. Explaining the time-series transition of the fluid pressure in this pressing operation, in the configuration of the present application, the fluid pressure P1 is ideally generated only during the pressing operation, and the fluid pressure P1 is generated during other expansion and contraction operations. It becomes zero. That is, the fluid cylinder 30 can be stationary if an equivalent reaction force is generated with respect to the gravity of the suspended component, and is also configured to operate 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 unnecessary. However, during the pressing operation, it is necessary to generate a pushing force that closes the plurality of stoppers to the openings 101 of the plurality of containers 100. At this time, the fluid pressure P1 is pressure-adjusted so as to have a required pushing force. In this embodiment, all the plugs are closed when the fluid pressure P1 is about 10 times that of the gravity of the suspended component.
After closing, by shortening the fluid cylinder 30, all the other shelf boards 11a except the bottom shelf board 11a are moved upward and returned to their original positions, and the shelf boards 11a located above and below each other are moved to their original positions. Widen the interval.

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

A cold trap 23 is provided in the collecting unit 20. The cold trap 23 has a tubular shape through which a cooling medium supplied from a cooling medium supply source (not shown) flows. The distribution of the cooling medium to the cold trap 23 is controlled by the control unit 40. As the cooling medium, for example, Freon gas R404A, silicone oil, or the like can be used.

The cold trap 23 is cooled by circulating 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 object to be dried F in the drying chamber 10 can be condensed and collected. The temperature of the cold trap 23 is appropriately set according to the type of the object 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 collecting portion 20 and condenses and collects the water sublimated from the object to be dried F.

A sluice valve 24 is provided at the communication port 21 of the collecting unit 20. The sluice valve 24 has a sluice body 24a capable of closing the communication port 21, a drive cylinder 24b for advancing and retreating the sluice body 24a with respect to the communication port 21, and a drive source 24c for driving the drive cylinder 24b. When the drive source 24c is driven and controlled by the control unit 40, the drive cylinder 24b advances and retreats the partition body 24a with respect to the communication port 21. When the partition body 24a is retracted from the communication port 21, the drying chamber 10 and the collecting unit 20 communicate with each other through the communication port 21. When the partition body 24a is advanced to close the communication port 21, the drying chamber 10 and the collecting portion 20 are blocked.

In the vacuum drying device 1, the vacuum drying process of the object to be dried F is performed as follows.

First, the object to be dried F is carried into the drying room 10 from a carry-in / carry-out room (not shown).
Next, after the drying chamber 10 and the loading / unloading chamber are separated into atmospheres under the control of the control unit 40, heat is removed so that the object to be dried F freezes using the heat medium supply source 13. The heat removal path is from the object F to be dried to the shelf plate 11a (the heat flow path is dominated by convection by the gas inside the drying chamber 10) and the heat medium (the heat flow path is dominated by heat conduction). Finally, heat is discharged from the heat removal source inside the heat medium supply source 13. When the amount of heat removed exceeds the phase transition temperature to the solid phase, the object 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 object to be dried F does not cause the collapse phenomenon, and then the heat is removed. At this time, the adjusting unit 12 supplies heat to the medium in the medium flow path 11b in the shelf plate 11a to heat each shelf plate 11a of the shelf 11 in the drying chamber 10. As a result, the object to be dried F placed on the shelf board 11a is heated, and the drying of the object to be dried F is promoted. The ice contained in the heated object F to be dried takes in latent heat from the object F to be dried and sublimates into steam. The generation of water vapor is a factor that raises the internal pressure. However, in this configuration, by opening the sluice valve 24 and using the cold trap 23 and the vacuum pump 22 inside the collecting unit 20, the internal pressure of the drying chamber 10 can be exhausted within the above pressure range. It has become. As the target value of the internal pressure, a value that does not cause the collapse phenomenon on the sublimation surface is required. Here, too low a pressure (internal pressure) causes a decrease in the amount of gas molecular weight intervening between the contact surfaces of the container 100 and the shelf 11, resulting in a proportional decrease in heat flux (that is, drying is delayed). Therefore, as an ideal target value of the internal pressure, it is preferable to set the maximum pressure that does not cause the collapse phenomenon in the range of the sublimation surface temperature of the object to be dried F, which will be described later. The collapse phenomenon is a phenomenon in which the three-dimensional structure of the solute confirmed after freeze-drying is not uniform. In other words, the collapse phenomenon is a phenomenon in which the sublimation surface is not uniformly dried in time series. The collapse phenomenon is an event that should be avoided from the aspect of product quality.

The vacuum pump 22 exhausts the gas in the drying chamber 10 containing water vapor via the collecting unit 20. Since the vacuum pump 22 is usually composed of a gas transport type vacuum pump, the exhaust speed with respect to water vapor is not sufficient. However, the cold trap 23 existing in the collecting unit 20 functions as a gas storage type vacuum pump. Therefore, the drying chamber 10 is exhausted by both the vacuum pump 22 and the cold trap 23. As a result, the drying chamber 10 can maintain a target internal pressure at the same time as ensuring a predetermined exhaust speed. The vacuum drying process of the object to be dried F in the vacuum drying device 1 as described above is only an example thereof, and the content of the process can be changed as appropriate.

The control unit 40 of the vacuum drying device 1 of the present embodiment adjusts the adjusting unit 12 based on the fluid pressure P2 of the fluid in the contracted side pipe 37 measured by the contracted side pressure sensor 39 when performing the vacuum drying process. It is used to control the heat flow to the object to be dried F and the temperature on 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 object to be dried F, and controls the adjustment unit 12 based on the weight of the shelf 11.

When the object to be dried F placed on the shelf 11 in the drying chamber 10 dries, the weight decreases according to the amount of sublimation (mass) thereof. When the weight of the object to be dried F is reduced, the total weight of the weight of the object to be dried F and the weight of the shelf 11 on which the object to be dried F is placed decreases. When the total weight of the object to be dried F and the shelf 11 decreases, the downward force acting from the shelf 11 on the fluid cylinder 30 that supports the shelf 11 to raise and lower the shelf 11 decreases. When the downward force acting on the fluid cylinder 30 in the direction of gravity 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 unit 40. The control unit 40 obtains (change) the weight of the object to be dried F by calculation based on the measured value of the fluid pressure P2, and controls the drying conditions of the object to be dried F by the adjusting unit 12.

As shown in FIG. 3, the control unit 40 functionally includes an input reception unit 41, a storage unit 42, a weight conversion unit 43, a temperature calculation unit 44, and a heating temperature control unit 45.
The input receiving unit 41 receives the 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 pipe 37 from the contraction side pressure sensor 39. The storage unit 42 stores various set values and the like necessary for controlling the heating of the object to be dried F in the adjusting 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 the shelf 11 is the load supported by the fluid cylinder 30. That is, the weight of the shelf 11 is the total weight of the weight of the object to be dried F and the weight of the shelf 11 on which the object 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 (weight of the shelf 11) is used in the specifications of the fluid cylinder 30 and in the experiment performed in advance. Obtained based on. The weight conversion unit 43 converts and acquires 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 the conversion formula obtained in advance. The purpose of the experiment performed in advance is to detect the weight fluctuation of the object to be dried F. Therefore, in an example of the above experiment, a state in which all the objects to be dried F are carried into the shelf 11 and the shelves 11 and all the objects to be dried F (all the mass suspended in the initial state) are suspended by the fluid cylinder 30. Keep and record the value of the fluid pressure P2 at this point as the initial value. Then, the weight (mass) is removed in units according to the required resolution, and the fluid pressure P2 corresponding to each weight is measured and recorded up to the end point (the weight of the object to be dried F in the final dried state). As a result, a conversion table (or a conversion formula that approximates this) may be created in advance and stored in the storage unit at 42.

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

Next, the temperature control method in the vacuum drying device 1 in the present embodiment will be described. In the temperature control method in the vacuum drying device 1 in the present embodiment, the heat transfer coefficient Kv of the container 100 containing the object to be dried F is obtained in advance. Since this heat transfer coefficient Kv takes a different value depending on the shape, material, and surface condition of the container, even if the container 100 is called a vial, it is necessary to obtain it each time if the shape or the like is different.
The heat transfer coefficient Kv is expressed by the following equation (1).

Here, ΔH: latent heat of sublimation of the object to be dried F, dm / dt: mass flow rate (mass flow rate) [kg / h] per unit time, N: placed on the shelf 11. The number of placed containers 100, Av: cross-sectional area per container 100 (vial cross-sectional area) [m ² ], Ts: shelf temperature [K], Tb: bottom center temperature of the container 100. Note that Av (cross-sectional area per container 100) does not mean the cross-sectional area inside each container 100, but the cross-sectional area of the outer shape. Further, the container 100 is premised on a substantially cylindrical shape (vial shape). However, when the container 100 has a shape other than the vial shape, the area surrounded by the outermost circumference of the contact point (stamp area) where the container 100 contacts the shelf 11 or the projected area of the bottom surface of the container 100 is used as the outer cross-sectional area. You can handle it. That is, the cross-sectional area Av per 100 containers is the area of the region where heat transfer by 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 equation (1) is obtained based on the following equations (2) and (3), which are the basic equations of the freeze-dried Heat mass Transfer (the equation (6) described later is also one of the basic equations. Is). 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 object F to be dried and the contact area (note that the contact). 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] per unit time.

In order to obtain the heat transfer coefficient Kv of the container 100, the container 100 containing pure water (ice: ΔH = 2800 [J / g]) whose sublimation latent heat ΔH is known is placed on the shelf 11 of the vacuum dryer 1. Install a predetermined number. Among the plurality of containers 100 placed on the shelf 11, the temperature of the object to be dried F (product temperature, bottom center temperature Tb of the container 100) is measured in the container 100 located at the center or the end of the shelf 11, for example. Install the product temperature sensor. More specifically, the temperature of the object to be dried F described above is the temperature on the interface side of the bottom surface of the object to be dried F in the central portion of the container 100. However, in the actual measurement, the 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 (the temperature at the center of the bottom surface of the container 100) is regarded as the temperature of the object to be dried F. It will be carried out in the meantime.

After that, the object to be dried F is dried in the drying chamber 10 under the same conditions as when actually freeze-drying (the number of containers 100, the internal pressure (vacuum degree) and the temperature of the drying chamber 10), and the shelves before and after drying. The weight of 11 is measured, and the amount of sublimated water vapor per unit time is dm / dt, that is, the rate of change in weight due to the sublimation of pure water in the container 100 is calculated. At this time, the freeze-drying treatment may be completed when the object to be dried F (pure water in this case) is sublimated by, for example, about 30 to 80%, and the weights of the plurality of containers 100 may be measured individually. .. In this case, it is possible to check the position dependence of the containers 100 on the shelf 11 instead of the average weight of the plurality of containers 100.
Further, for the measurement of the shelf temperature Ts, the supply side temperature sensor 19A and the recovery side temperature sensor 19B provided in the adjusting unit 12 are used. As the shelf temperature Ts, an average value of the measured value of the supply side temperature sensor 19A and the measured value of the recovery side temperature sensor 19B can be used. However, the fact that there is 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 as a freeze-drying device. That is, it is desired that the medium is designed so that a sufficient flow rate can be secured, and that the absolute value of the difference during freeze-drying (during stable operation excluding the initial stage) is less than 1.5 ° C. In this case, there is no inconvenience even if any of the temperature sensors is used as a representative value.

Next, according to the above equation (1), the calculated sublimation water vapor amount dm / dt value, the shelf temperature Ts measured value, the bottom center temperature Tb measured value of the container 100, and the number of containers 100 placed on the shelf 11 N, the cross-sectional area Av (known) per 100 containers is substituted. As a result, the heat transfer coefficient Kv of the container 100 can be obtained. The obtained heat transfer coefficient Kv of the container 100 is stored in the storage unit 42 for use in the freeze-drying treatment of the object to be dried F, which is a production operation described later.

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

First, as shown in FIG. 4, the control unit 40 receives an input of 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). For this purpose, as described above, the weight of the shelf plate 11a supported by the fluid cylinder 30 is converted and obtained from the measurement result of the fluid pressure P2 based on the conversion formula obtained in advance.

Next, the control unit 40 calculates the temperature of the object to be dried F in the temperature calculation unit 44 based on the acquired weight of the shelf 11 (step S3). In the present embodiment, the temperature calculation unit 44 determines the sublimation latent heat ΔH of the object 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 obtained in advance. As the temperature of the object to be dried F, the bottom center temperature Tb [K] of the container 100 is calculated based on the above. As the value of the latent heat of vaporization ΔH, the value of the solvent of the object to be dried F may be used. However, when the value of the latent heat of sublimation ΔH fluctuates significantly depending on the solute, a value obtained by multiplying the correction coefficient obtained by conducting an experiment in advance by the value of the solvent may be used.

The lower formula (4) obtained based on the above formulas (2) and (3) is used to calculate the bottom center temperature Tb of the container 100.

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

Further, the thickness of the frozen layer L2 L _{ice (see} Fig. 2) from the weight of the material to be dried F accommodated in the container 100 (known), based on the weight m of the object to be dried F sublimated (sublimation amount) calculated Will be done. Thereby, the bottom center temperature Tb of the container 100 which is calculated by the equation (4), by the following equation (5) can be converted to a temperature T _ice sublimation surface Lf of the material to be dried F. As a condition, it is premised that the volume of the solution forming the weight m of the initial object F to be dried at the time of freezing is known, and the internal shape (usually a cylinder) of the container 100 is known. That, L _ice at the time prior to sublimating the solvent is known thickness at the inside of the container 100, of the weight m of the object to be dried F, and all the mass corresponding to the weight of the solvent sublimed At this point, the thickness of the _{Lice is zero.} For example, when 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 object to be dried F and _{the thickness of Lice} have a linear proportional relationship (relationship represented by a linear function). Therefore, the use of the proportional relation, it is possible to calculate the thickness L _ice readily frozen layer L2 from the weight of the obtained rack 11.

Here, _Kice : the heat transfer coefficient [J / s · m · K] of the frozen layer L2. This value is stored in the storage unit 42 as a known value from the beginning. For this value, the value obtained by literature or experiment is used.

Thus, in step S3, the temperature calculation section 44, as the temperature of the material to be dried F, bottom center temperature Tb of the container 100, and the temperature T _ice sublimation surface Lf of the material to be dried F, is obtained by conversion be able to.

The control unit 40 controls the heating operation of the shelf 11 in the adjustment unit 12 based on the temperature of the object to be dried F calculated by the temperature calculation unit 44 in step S3 by the heating temperature control unit 45 (step S4). .. Here the temperature of the object to be dried F to be used in may be any of the temperature T _ice sublimation surface Lf of the bottom core temperature Tb, and the material to be dried F of the container 100.

The specific method of heating the shelf 11 in the adjusting unit 12 based on the temperature of the object F to be dried in step S4 is not limited in any way. For example, the heating temperature controller 45, so that the temperature of the material to be dried F (temperature T _ice sublimation surface Lf bottom center temperature Tb or article to be dried F, the container _100), to maintain the following collapse temperature, heating It is preferable that the temperature control unit 45 controls the operation of the adjustment unit 12. Further, in order to improve the efficiency of the vacuum drying process, in the heating temperature control unit 45, the heating temperature control unit 45 adjusts the temperature of the object to be dried F so that it is equal to or lower than the collapse temperature and is as high as possible. It is preferable to control the operation of twelve. As the temperature reference, instead of the collapse temperature of the object to be dried F, the glass transition point, melting point, eutectic point, temperature when used as a product, etc. of the object to be dried F may be used as a reference. In other words, for example, the material properties of the drug substance and the pharmaceutical may be used as the reference for the temperature.

As described above, according to the vacuum drying device 1 according to the present embodiment, the fluid supply / discharge system 35 that supplies / discharges fluid to the fluid cylinder 30 that raises and lowers the shelf 11 on which the object to be dried F is placed is provided. It is provided and includes a contraction side pressure sensor 39 for measuring 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 suspended object F to be dried and the shelf 11 decreases. To do. Then, the downward force acting on the shelf 11 in the direction of gravity also decreases with respect to the fluid cylinder 30 that supports the shelf 11 in order to raise and lower the shelf 11. As a result, the fluid pressure P2 in 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, the weight of the object to be dried F is reduced due to drying based on the change in the measurement result of the contraction side pressure sensor 39. Can be detected. The change in weight of the object to be dried F due to drying and the change in fluid pressure P2 of the fluid cylinder 30 are directly correlated with each other. Therefore, the dry state of the object to be dried F can be detected more directly, and the dry state of the object to be dried F can be grasped with higher accuracy.

Further, the vacuum drying device 1 further includes an adjusting unit 12 for adjusting the temperature Ts of the shelf 11 and a controlling unit 40 for controlling the adjusting unit 12 based on the measurement result of the contraction side pressure sensor 39.
In 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 adjusting unit 12 based on the change in the fluid pressure P2 of the fluid cylinder 30, so that the object F to be dried is adjusted according to the dry state of the object F to be dried. The temperature Ts of the shelf 11 for drying the fluid 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 supporting the object 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, 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, the total weight of the weight of the object to be dried F and the own weight of the shelf 11 is converted and obtained to be dried. It is possible to grasp the change in the dry state of the object F. Therefore, the temperature Ts of the shelf 11 can be appropriately adjusted according to the dry state of the object F to be dried.

Further, the control unit 40 of the shelf 11 is based on the sublimation latent heat ΔH of the object 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 the temperature Ts.
In such a configuration, the temperature of the object F to be dried (the bottom center temperature Tb of the container 100) is based on the latent heat of sublimation ΔH of the object F to be dried, the weight of the shelf 11, the cross-sectional area Av of the container 100, and the heat transfer coefficient Kv. , The temperature of the sublimation surface Lf of the object to be dried F ( _Tice ) can be calculated and obtained. Thereby, by adjusting the temperature Ts of the shelf 11 according to the temperature state of the object to be dried F, the object to be dried F can be dried 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 object to be dried F becomes equal to or lower than the collapse temperature.
If the temperature of the object to be dried F exceeds the collapse temperature even in only a part of the region, a collapse phenomenon occurs in which the portion of the object to be dried F in which the moisture is frozen shrinks, and the object to be dried F is dried well. However, the quality deteriorates. In the configuration of the present embodiment, the temperature Ts of the shelf 11 is appropriately adjusted based on the change of the fluid pressure P2 of the fluid cylinder 30, so that the temperature of the object to be dried F, particularly the sublimation surface temperature is equal to or lower than the collapse temperature. By maintaining the temperature, the object to be dried F can be satisfactorily dried.

According to the temperature control method of the shelf 11 in the vacuum drying device 1 according to the present embodiment, the fluid pressure P2 of the fluid in the fluid supply / discharge system 35 that supplies / discharges the fluid to the fluid cylinder 30 that raises and lowers the shelf 11 is used. , 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 acting on the shelf 11 in the direction of gravity decreases with respect to the fluid cylinder 30 that supports the shelf 11 in order to raise and lower the shelf 11. As a result, the fluid pressure in 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, the weight of the object to be dried F is reduced due to drying based on the change in the measurement result of the contraction side pressure sensor 39. Can be detected. The change in weight of the object to be dried F due to drying and the change in fluid pressure P2 of the fluid cylinder 30 are directly correlated with each other. Therefore, the dry state of the object to be dried F can be detected more directly, and the dry state of the object to be dried F can be grasped with higher accuracy.

Further, according to the temperature control method of the shelf 11 in the vacuum drying device 1, the fluid pressure P2 is converted into the weight of the shelf 11 supporting the object to be dried F, and the temperature Ts of the shelf 11 is calculated based on the weight of the shelf 11. Control.
In such a configuration, since the own weight of the shelf 11 is known and the own weight attached to the object to be dried F can also be known, the fluid pressure P2 of the fluid cylinder 30 allows the shelf 11 to support the object to be dried F. By converting the weight, that is, the total weight of the object to be dried F and the shelf 11, the change in the dry state of the object to be dried F can be grasped. Therefore, the temperature Ts of the shelf 11 can be appropriately adjusted according to the dry state of the object F to be dried.

According to the method for adjusting the temperature of the shelf 11 in the vacuum drying device 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 object 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 dries, the total weight of the object to be dried F and the shelf 11 on which the object to be dried F is placed decreases. Thereby, the dry state of the object to be dried F can be grasped from the weight of the shelf 11 supporting the object to be dried F. Therefore, the dry state of the object to be dried F can be detected more directly than the method of measuring the amount of sublimated water vapor, for example, so that the dry state of the object to be dried F can be grasped with higher accuracy. It becomes.

Further, according to the temperature control method of the shelf 11 in the vacuum drying device 1 according to the present embodiment, the object to be dried F is placed on the shelf 11 in a state of being housed in the container 100, and the object 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 (measurement result of 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, based on the weight of the shelf 11, the sublimation latent heat ΔH of the object to be dried, 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, the object to be dried F The temperature can be calculated and obtained. Thereby, by adjusting the temperature Ts of the shelf 11 according to the temperature state of the object to be dried F, the object to be dried F can be dried under appropriate conditions.

Further, according to the temperature control method of the shelf 11 in the vacuum drying device 1 according to the present embodiment, the temperature Ts of the shelf 11 is set based on the weight of the shelf 11 so that the temperature of the object to be dried F is equal to or lower than the collapse temperature. Control.
In such a configuration, when the temperature of the object to be dried exceeds the collapse temperature, a collapse phenomenon occurs in which the portion where the moisture of the object to be dried F is frozen shrinks, and the object to be dried F is dried well. It disappears. By appropriately adjusting the temperature Ts of the shelf 11 based on the change in the fluid pressure P2 of the fluid cylinder 30 and maintaining the temperature of the object to be dried F to be equal to or lower than the collapse temperature, the object to be dried F can be dried. Can be done well.

(Modified example of the embodiment)
In the above embodiment, when calculating the temperature of the object to be dried F based on the weight of the shelf 11 in step S3, the temperature calculation unit 44 determines the sublimation latent heat ΔH of the object to be dried F and the weight of the shelf 11 (contracted side). The temperature of the object 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, but the temperature is not limited to this.

For example, in step S3, in order to calculate the temperature of the object 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 for the object to be dried F, and the product per product in the container 100 are used. 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) is different from Av and means the internal cross-sectional area of each container 100.

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

After that, the object to be dried F is dried under the same conditions (internal pressure (vacuum degree) and temperature of the drying chamber 10) as in the actual freeze-drying treatment in the drying chamber 10, and the weight of the shelf 11 before and after drying is reduced. Measure and calculate the sublimation water vapor amount dm / dt per unit time. At this time, when the object to be dried F is sublimated by, for example, about 30 to 50%, the freeze-drying treatment may be completed and the weights of the plurality of containers 100 may be individually measured. In this case, the position dependence of the container 100 on the shelf 11 can be examined instead of the average weight of the container 100.

Next, the water vapor transfer resistance Rp is calculated by the formula (7) obtained by modifying the following formula (6).

Here, Ap: product cross-sectional area per container 100 [m ² ], _Piece : sublimation surface pressure [Pa], P _DC : internal pressure of drying chamber [Pa], Rp: water vapor transfer resistance [Pa · m ² · s / g]. In FIG. 2, the sublimation surface pressure _Picke is the dried layer L1 generated in the upper layer of the object to be dried F in the container 100 due to the sublimation of water, and the dried layer L1 is still frozen under the dried layer L1. This is the pressure acting on the sublimation surface Lf formed at the boundary between the frozen layer L2 and the frozen layer L2. Equation (6) is based on the moisture is sublimated by the differential pressure of the internal pressure _{P DC} sublimation surface pressure _{P ice} and the drying chamber (equation (6) is one of the basic formula for Heat mass Transfer lyophilization is there).

In equation (7), and substitutes the calculated value of sublimated water vapor dm / dt, product cross-sectional area Ap per one of the container 100, the sublimation surface pressure _{P ice} of the material to be dried F, the internal pressure _{P DC} of the drying chamber .. As a result, the water vapor transfer resistance Rp is obtained. Note In practice, as shown in Equation (7), the sublimation surface pressure _{P ice} can be represented by the temperature _{T ice} sublimation surface Lf of the material to be dried F. Wherein the temperature _{T ice,} for example, based on the above equation (5) can be obtained from the bottom center temperature Tb of the container 100.

Since the water vapor transfer resistance Rp differs depending on the material of the object F to be dried, it is preferable to calculate the water vapor transfer resistance Rp for each material in the same manner as described above. Further, since the water vapor transfer resistance Rp depends 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. Further, even if a function showing the correlation between the thickness of the dry layer L1 and the water vapor transfer resistance Rp is set, and the water vapor transfer resistance Rp according to the thickness of the dry layer L1 is obtained based on this function. Good. Such a function is, for example,
_{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 Lice} 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 the present embodiment, the water vapor transfer resistance Rp is the sum of the water vapor transfer resistance of the already dried layer and the water vapor transfer resistance of the stopper.

After obtaining the water vapor transfer resistance Rp in this way, the vacuum drying device 1 actually executes the freeze-drying treatment of the object to be dried F.
As shown in FIG. 4, in the same manner as in the above embodiment, the control unit 40 is a signal indicating the measurement result of the fluid pressure P2 in 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).

Next, the control unit 40 calculates the temperature of the object to be dried F in the temperature calculation unit 44 based on the acquired weight of the shelf 11 (step S3). In this modification, the temperature calculation section 44 of the controller 40, the internal pressure _{P DC} of the drying chamber 10, the water vapor transfer resistance Rp of the material to be dried F obtained above, the number of the container 100 N, per one of the containers 100 Based on the product cross-sectional area Ap and the sublimation water vapor amount dm / dt calculated from the weight of the shelf 11 converted in step S2, the temperature of the object to be dried F is determined by the following formula (8). It calculates the temperature _{T ice} for sublimation surface Lf.

Further, based on the above equation (5), the temperature T _ice sublimation surface Lf of the material to be dried F, in terms of bottom core temperature Tb of the container 100, which may be a temperature of the material to be dried F.
In this manner, as the temperature of the material to be dried F, acquires the temperature T _ice or bottom center temperature Tb of the container _100, the sublimation surface Lf of the material to be dried F.

After that, in step S4, as in the above embodiment, the heating temperature control unit 45 heats the shelf 11 in the adjusting unit 12 based on the temperature of the object to be dried F calculated by the temperature calculation unit 44 in step S3. Control the operation.

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

The technical scope of the present invention is not limited to the above-described embodiment, and various modifications 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 acquire the weight of the shelf 11, but the present invention is not limited to this. The extension side pressure sensor 38 may measure the fluid pressure of the contraction side pipe 37, or the fluid pressure P2 in the contraction side pipe 37 measured by the contraction side pressure sensor 39 and the extension side pressure sensor 38 may be used. The weight of the shelf 11 may be converted and obtained based on the pressure difference from the fluid pressure in the extension side pipe 36 to be measured.

Further, in the above embodiment, based on the fluid pressure P2 in the contraction side pipe 37 measured by the contraction side pressure sensor 39, the temperature of the object to be dried F (the bottom center temperature Tb of the container 100 or the object to be dried F). to obtain a temperature T _ice) sublimation surface Lf, and to perform the control of the regulatory unit 12 is not limited to this. Based on the fluid pressure P2 in the contraction side pipe 37 measured by the contraction side pressure sensor 39, the adjusting unit 12 may be controlled using the sublimation surface pressure Picke of the object to be dried F as a key.

In addition, it is possible to replace the components in the embodiment with well-known components as appropriate without departing from the spirit of the present invention, and the above-mentioned modifications may be appropriately combined.

1 Vacuum drying device 10 Drying chamber 11 Shelf 12 Adjusting unit 20 Collection unit 30 Fluid cylinder 35 Fluid supply / discharge system 39 Compression side pressure sensor (measurement unit)
40 Control unit 100 Vial F To be dried ΔH Sublimation latent heat Kv Heat transfer coefficient L1 Dried layer P2 Fluid pressure Rp Water vapor transfer resistance Ts Temperature Ts Temperature

Claims (12)

Drying room and
A shelf placed in the drying chamber and on which the object to be dried is placed,
A fluid cylinder that raises and lowers the shelf,
A fluid supply / discharge system that supplies / discharges fluid to the fluid cylinder,
A measuring unit provided in the fluid supply / discharge system and measuring the fluid pressure of the fluid,
A vacuum drying device including a collecting unit for collecting water sublimated from the object to be dried. An adjusting unit that adjusts the temperature of the shelf,
The vacuum drying device according to claim 1, further comprising a control unit that controls the adjustment unit based on the measurement result of the measurement unit. The control unit
At each of the two different times, the measurement result of the measuring unit was converted into the weight of the shelf supporting the object to be dried.
The sublimation rate of the object to be dried was calculated from the difference between these two times and the weight.
The estimated temperature of the object to be dried is calculated based on the sublimation rate.
The vacuum drying device according to claim 2, wherein the adjusting unit is controlled so that the estimated temperature becomes equal to or lower than a preset threshold value. The object to be dried is placed on the shelf in a state of being contained in a container.
The vacuum drying device according to claim 3, wherein the control unit calculates the estimated temperature based on the sublimation latent heat of the object to be dried, the sublimation rate, the cross-sectional area of the container, and the heat transfer coefficient of the container. The object to be dried is placed on the shelf in a state of being contained in a container.
The vacuum drying according to claim 3, 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. apparatus. The vacuum drying device according to any one of claims 3 to 5, wherein the threshold value is the collapse temperature. Drying room and
A shelf placed in the drying chamber and on which the object to be dried is placed,
A fluid cylinder that raises and lowers the shelf,
A method of adjusting the temperature of the shelf in a vacuum drying device including a collecting unit for collecting water sublimated from the object to be dried.
A method for adjusting the temperature of a shelf in a vacuum drying device that adjusts the temperature of the shelf based on the fluid pressure of the fluid in a fluid supply / discharge system for supplying / discharging a fluid to the fluid cylinder. At each of the two different times, the fluid pressure was converted to the weight of the shelf supporting the object to be dried.
The sublimation rate of the object to be dried was calculated from the difference between these two times and the weight.
The estimated temperature of the object to be dried is calculated based on the sublimation rate.
The method for adjusting the temperature of a shelf in the vacuum drying device according to claim 7, wherein the temperature of the shelf is controlled so that the estimated temperature becomes equal to or less than a preset threshold value. Drying room and
A shelf placed in the drying chamber and on which the object to be dried is placed,
A method of adjusting the temperature of the shelf in a vacuum drying device including a collecting unit for collecting water sublimated from the object to be dried.
At each of the two different times, the weight of the shelf supporting the object to be dried was measured.
The sublimation rate of the object to be dried was calculated from the difference between these two times and the weight.
The estimated temperature of the object to be dried is calculated based on the sublimation rate.
A method for adjusting the temperature of a shelf in a vacuum drying device that adjusts the temperature of the shelf so that the estimated temperature is equal to or lower than a preset threshold value. The object to be dried is placed on the shelf in a state of being contained in a container.
Temperature control of a shelf in the vacuum drying apparatus according to claim 8 or 9, wherein the estimated temperature is calculated based on the sublimation latent heat of the object to be dried, the sublimation rate, the cross-sectional area of the container, and the heat transfer coefficient of the container. Method. The object to be dried is placed on the shelf in a state of being contained in a container.
The shelf in the vacuum drying apparatus according to claim 8 or 9, wherein the estimated temperature is calculated 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. Temperature control method. The method for adjusting the temperature of a shelf in a vacuum dryer according to any one of claims 8 to 11, wherein the threshold value is the collapse temperature.

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