JP3869297B2 - Temperature control device for shelf in freeze dryer - Google Patents

Description

[0001]
[Technical field to which the invention belongs]
In the present invention, a material to be dried is placed on a temperature-adjustable shelf mounted in parallel in a drying cabinet of a freeze-drying apparatus, and sublimation steam is supplied while supplying sublimation heat from the shelf. The present invention relates to an improvement in means for controlling the temperature of shelves mounted in multiple stages in a drying cabinet in a freeze dryer that condenses, collects and dries in a trap provided in a vacuum chamber.
[0002]
[Prior art]
As shown in FIG. 1 and FIG. 2, freeze-drying of the material to be dried performed using a freeze dryer opens the door 1 of the drying chamber A that can be maintained at a predetermined degree of vacuum, and in the drying chamber A in multiple stages. A material to be dried is placed on each of the shelf-controlled shelves a that are temperature-controlled, and sublimated water vapor is sublimated by supplying sublimation heat from the shelf a, and the sublimated water vapor is supplied to the vacuum piping port 2. Is pulled out to the vacuum chamber where the trap is disposed and collected in the trap.
[0003]
At this time, when the material to be dried is a pharmaceutical product, the material to be dried is injected into a small container such as a vial or an ampule when the material to be dried is a medicine. This is done by feeding the container with a loading device.
[0004]
In the loading by loading, a cart that can enter the drying chamber A is provided with a plurality of shelves corresponding to the shelves a in the drying chamber A, and small containers are placed on these shelves. When the groups are arranged and mounted, and these small container groups are transferred onto the respective shelf steps a in the drying chamber A at the same time by the entry of the carriage, and the shelves installed in the drying chamber A Each of the stages a is hung by a hanging tool while maintaining a predetermined shelf interval, and is lowered so that it is superposed and folded at the bottom of the drying chamber A. A small door is installed in the part where the entrance is close to the lower end of the door that opens and closes the opening on the front of the drying chamber A, and a small container is inserted from here as disclosed in Japanese Patent No. 2928107. Align small containers on the shelves and place them on the shelves, and then transfer them one by one to shelf a In some cases the trays by lifting one by one stage to insert each shelf.
[0005]
When a small container group containing a material to be dried is placed in a batch for each shelf or in a batch for each shelf and is transferred while the shelf is cooled, the shelf is cooled in advance to the shelf a The material to be dried in the small container mounted on the vertical axis is as shown in the model shown in FIG. Can be formed.
[0006]
However, in this method, that is, in each row or all-stage batch insertion method, an aligner for the depth direction of the shelf level a is required, and the alignment space is required before the drying chamber.
[0007]
The loading method in which the small container is pushed in front of the drying cabinet by the width of the shelf a, for example, a unit group in which a predetermined number of units are arranged in a row, is not subject to the size restriction before the drying cabinet, and the loading mechanism is Can be simple.
[0008]
[Problems to be solved by the invention]
By repeating the process of pushing a predetermined number of small containers as a unit group in a row in the width direction of the shelves for shelves arranged in parallel in the drying cabinet in multiple stages, small containers on the front of the shelves When the shelves are cooled to a freezing temperature that freezes the material to be dried in advance, when the small containers are pushed unit by group, the small containers that have already been pushed in are arranged. The impulsiveness that occurs when it comes into contact may cause sudden freezing in the material to be dried in the small container.
[0009]
The material to be dried in the small container placed on the shelf a is cooled from the bottom surface of the small container because the shelf a is cooled to about minus 40 degrees C. As shown in the model shown in FIG. 3, vertical ice crystals are formed, which is excellent in solubility, but due to the shock received by the contacts of the small containers during the alignment operation on the shelf of the small containers, Sudden freezing phenomenon, where ice crystallization suddenly occurs, causes freezing of independent pore type, as in the model shown in Fig. 4. There is a problem that comes into play.
[0010]
The present invention has been made to solve this problem, and the small containers filled with the material to be dried without causing sudden freezing are aligned on the shelf stage by pushing one row at a time. The object is to provide a new means for enabling charging.
[0011]
[Means for Solving the Problems]
When loading a group of small containers filled with material to be dried onto a shelf in the drying cabinet, loading will prevent sudden freezing even if there is a shock due to contact between the small containers. Has obtained knowledge that it can be solved by keeping the cooling temperature of the drying cabinet shelf at a temperature that does not cause freezing in the material to be dried in the small container to be loaded. On the other hand, when the predetermined number of small containers have been charged, by controlling so that the cooling temperature of the shelf is rapidly set to a predetermined minus 40 degrees C, freeze drying of the material to be dried in the small containers It has been found that it can be carried out efficiently in the state of forming beneficial vertical ice crystals.
[0012]
For this reason, according to the means of the present invention, the heat medium cooled to a temperature that does not cause the material to be dried to freeze is sent to the circuit of the heat medium connected to the shelves arranged in multiple stages in the drying cabinet. When a small container is loaded into a shelf by loading a circuit for feeding and a circuit for feeding a heat medium cooled to a predetermined temperature via a switching valve, Pre-cool the temperature to a temperature that does not cause freezing of the material to be dried, and when the small container has been charged, the shelf should be rapidly cooled to the specified temperature. It provides a means to control the temperature.
[0013]
At this time, when charging small containers one by one with respect to the shelves arranged in parallel, the entire shelves are pre-cooled to a temperature at which the material to be dried does not freeze, and the small containers are loaded. Control is performed so that a predetermined cooling temperature is sequentially obtained from the shelf that has been inserted. Of course, in order to obtain the above-mentioned vertical ice crystal of FIG. 4 by rapidly cooling, it may be determined by using a large refrigerator and a heat exchanger or using a cold storage function, depending on the heat capacity and cost of the apparatus. The pre-cooling circuit may be partially mixed from the regenerator circuit and appropriately generated by mixing, or cold heat may be produced by another refrigerator.
[0014]
DETAILED DESCRIPTION OF THE INVENTION
Next, embodiments will be described with reference to the drawings of the embodiments.
FIG. 5 is a development view of a heat medium passage pipe circulated to a shelf in a drying cabinet of a freeze dryer that implements the temperature control means of the shelf according to the present invention, in which A is a drying cabinet, a ... shows the shelf which can be shelf-arranged in parallel in the drying cabinet.
[0015]
The drying cabinet A includes a door 1 that opens and closes at an opening that opens to the front side, as in the conventional drying cabinet A shown in FIGS. 1 and 2, and the interior of the cabinet is sealed by closing the door 1. The interior of the chamber is maintained at the degree of vacuum required for vacuum drying by the operation of the evacuation system connected to the vacuum piping port 2 via the valve mechanism and the piping 3, and the piping 3 connected to the vacuum piping port 2 It is a normal one configured so as to be connected to the trap chamber 4 storing the water vapor condensing unit 40 through a valve mechanism.
[0016]
In the drying cabinet A, the shelves a, which are arranged in multiple stages, have pipes for circulating a heat medium (heat medium fluid) incorporated therein, and are heated by a heat medium fed from the heat medium circuit 5 connected thereto. It is usual that the temperature of the shelf surface can be adjusted as desired.
[0017]
The heat medium circuit 5 that circulates the heat medium through the pipe line incorporated in the shelf stage a keeps the shelf surface of the shelf stage a in a frozen state in order to freeze-dry the material to be dried placed thereon. The circuit 5a that feeds the heat medium cooled to, for example, minus 40 degrees C, and the shelf surface of the shelf stage a are set to a temperature that does not cause the material to be dried placed thereon to freeze. There are two circuits, for example, a circuit 5b for feeding a preheated cooling medium cooled to minus zero degrees, and these circuits 5a and 5b are connected to the heat medium pipe in the shelf stage a via the three-way valve 6. By connecting the circuit 5b through which the heat medium cooled to minus zero degrees through the switching operation of the three-way valve 6 is connected to the pipe line in the shelf a, Temperature in a range where the shelf surface does not freeze the material to be dried placed on it The circuit 5a through which the heat medium cooled to minus 40 degrees C is connected to the pipe line in the shelf a by switching the three-way valve 6 to be in a precooled state. The surface is cooled to a temperature at which the material to be dried placed on it can be frozen and lyophilized.
[0018]
The heat medium circuit 5 is switched by the three-way valve 6 to a circuit 5b for pre-cooling the shelf a and a circuit 5a for cooling the shelf a to a temperature at which the material to be dried is kept frozen for freeze-drying. In this example, the switching control for the pipelines in the shelf a which is shelved in multiple stages in the drying chamber A can be performed separately for each shelf a.
[0019]
That is, in these two circuits 5a and 5b, the respective inlet side and outlet side branch to the branch circuits 50 corresponding to the pipes of each shelf stage a by the flow divider b, and these branch circuits 50. The inlet pipes c and outlet pipes d of the stage a are connected to the outlet pipes d through different three-way valves 6, whereby the three-way valves 6 corresponding to the respective shelf stages a are made independent. By operating individually, the switching control between the pre-cooling circuit 5b and the freeze-drying circuit 5a connected to the multi-stage shelf a ... can be performed for each shelf a. .
[0020]
In the embodiment shown in FIG. 5, the cooling medium in each circuit 5a, 5b is cooled to a desired temperature by placing the shelf surface of the shelf a and the material to be dried placed thereon in a frozen state. A circuit 5a that circulates a freeze-drying heat medium that is cooled to a temperature to be held, and a precooling that cools the shelf surface of the shelf a to a temperature that does not cause freezing of the material to be dried placed thereon. Is provided with a heat medium temperature control circuit 5c connected to the circuit 5b for circulating the heat medium via the valve mechanisms 51 and 52, and is connected to the refrigerator 90 via the refrigerant pipe 91 for cooling. The heat medium in the temperature control circuit 5c is cooled by heat exchange by the coolers 92 and 92, and a heater 93 equipped with a heater is installed in the temperature control circuit 5c. The temperature adjustment circuit 5 is exchanged by heat exchange by the heater 93. The heat medium of the inner leave adapted to heat, so that to circulate the heat medium adjusted to a desired temperature in the temperature control circuit 5c circuit 5b and circuit 5a for lyophilization for pre-cooling.
[0021]
When adjusting the heat medium to be circulated to the freeze-drying circuit 5a in the temperature control circuit 5c, the temperature of the heat medium in the circuit 5c is the temperature at which the shelf surface of the shelf a is to be cooled, for example, minus 40. When it is intended to cool to degree C, it is adjusted to about minus 70 degree C, which is much lower than the temperature, and this is passed through the freeze-drying circuit 5a and the heating medium pipe in the shelf a. The shelf a can be quickly cooled to a predetermined temperature. The heat medium in the pre-cooling circuit 5b is cooled by mixing the heat medium in the freeze-drying circuit 5a at a desired ratio by opening the valve mechanism 52. In FIG. 5, P1, P2, and P3 are circulation pumps provided in the heat medium circuit 5.
[0022]
Next, FIG. 6 shows the arrangement of the small containers filled with the material to be dried in the drying chamber A in which the temperature of the shelf surface of the shelf a set in the chamber as described above is controlled by the two circuits 5a and 5b. FIG. 2 is a plan view of a loading device B for loading, in which A is a drying cabinet, A ′ shown by a broken line is an inner wall surface of the drying cabinet A, a is a shelf laid in the drying cabinet A, 1 is an open / close door that closes the opening on the front side of the drying cabinet A, 10 is a small door that opens and closes an entrance provided in a part of the open / close door 1, and 70 is a loading device disposed on the front of the entrance. B pusher, 71 is a transfer line made up of a conveyor in which small containers such as vials into which the material to be dried is injected are arranged in a row and sequentially sent between the inlet and the pusher 70, and 72 advances and retracts the pusher 70. 1 shows a hydraulic cylinder device.
[0023]
The drying chamber A is provided with a small, small entrance w as shown by a broken line in FIG. 7 at a position near the opening / closing door 1 that closes the front side thereof. Is provided with a small door 10 that slides up and down to open and close the inlet w.
[0024]
Further, for example, as shown in FIG. 9, the shelves a... Shelved in the drying cabinet A are arranged on a lifting rod 80 that is suspended on the ceiling of the drying cabinet A so as to be lifted by a lifting mechanism. The uppermost shelf a is suspended through a suspension rod 81, the next shelf a is suspended from the shelf a through a suspension rod 82, and the next shelf a is suspended by a suspension rod 83. It is suspended in a state of being connected in a chain shape by being suspended through the doors, and when the elevating rod 80 is lowered, all the shelves a are in a state of being stacked or superposedly closely stacked and dried. At this time, the shelf surface of the uppermost shelf a is aligned with the lower edge of the lip of the loading port w, and from this state, the lifting rod 80 is moved to the shelf a. By raising by the shelf interval, the shelf surface of the next shelf stage a occupies a position aligned with the lower edge of the loading port w, Are as the trays a go opposite to sequentially cut behalf spout w in the lift rod 80 sequentially raising increments shelf spacing portion of.
[0025]
Then, the pusher 70 of the loading device B repeats the operation of pushing a predetermined number of small containers sent in a line by the transfer line 71 into the loading port w, so that the shelf facing the loading port w When a predetermined number of small containers are aligned and loaded on the entire surface of the shelf of stage a, the shelf stage a is lifted by one stage so that the next shelf a is switched to the loading port w. Therefore, the small container is charged again by the operation of the pusher 70 of the loading device B, and the material to be dried is loaded to all the shelves a ... by repeating this operation.
[0026]
【The invention's effect】
As described above, the means according to the present invention enables the shelf to be placed in the drying cabinet to be placed on the shelf surface of the shelf by supplying the heat medium at about minus zero degrees by switching the heat medium circuit. The material to be dried is pre-cooled to a temperature that does not cause freezing of the dried material, and the material to be dried is charged in that state. When the charging is completed, the heating medium circuit is switched to about minus 40 degrees C. Since the cooled heat medium is supplied to the shelf to be freeze-dried, when the small containers into which the material to be dried is injected are loaded onto the shelf in the drying cabinet by loading. Even if there is a shock due to contact between small containers, it can be inserted without causing sudden freezing.
[Brief description of the drawings]
FIG. 1 is a front view showing a state in which a door of a drying cabinet of a freeze dryer is opened.
FIG. 2 is a vertical sectional side view of the same.
FIG. 3 is a cross-sectional view of a model of ice crystal shape generated in a material to be dried when the material to be dried in a small container is cooled on a shelf.
FIG. 4 is a cross-sectional view of an ice crystal shape model of sudden freezing generated in a material to be dried by shock caused by contact between small containers at the time of loading.
FIG. 5 is a development view of a heat medium circuit according to an embodiment of the present invention means.
FIG. 6 is a plan view of the loading device according to the embodiment.
FIG. 7 is a front view of the drying cabinet of the embodiment.
FIG. 8 is a side view of the embodiment.
FIG. 9 is a longitudinal sectional view of a drying cabinet of another embodiment same as the above.
[Explanation of symbols]
A ... Dryer, A '... Inner wall surface of the dryer, B ... Loading device, P1, P2, P3 ... Circulation pump, a ... Shelf, b ... Shunt, c ... Inlet pipe, d ... Outlet pipe, w ... Inlet 1, 1 Open / close door, 10 Small door, 2 Vacuum pipe port, 3 Piping, 4 Trap chamber, 40 Steam condensing unit, 5 Heat transfer circuit, 5a / 5b Circuit, 5c Temperature control Circuit, 50 ... Branch circuit, 51/52 ... Valve mechanism, 6 ... Three-way valve, 70 ... Pusher, 71 ... Transfer line, 72 ... Hydraulic cylinder device, 80 ... Lifting rod, 81/82/83 ... Hanging rod, 90 ... Refrigerator, 91 ... refrigerant circuit, 92 ... cooler, 93 ... heater.

Claims (1)

A circuit for supplying a heat medium cooled to a temperature within a range where the material to be dried is not frozen to a conduit of the heat medium incorporated in the shelf in the drying cabinet, and a predetermined temperature for freeze-drying the material to be dried When the small container group into which the material to be dried is injected is loaded into the shelf by loading, a circuit for feeding the cooled heat medium is connected to the shelf by loading. The heat medium that has been stored at that temperature is supplied from the circuit that supplies the heat medium that has been cooled to a range that does not cause freezing of the material to be dried to the heat medium pipe line, and is pre-cooled. When the charging of the small container group to the shelf is completed, the circuit is switched to a circuit that feeds the heat medium cooled to a predetermined temperature, and the heat medium held at that temperature is fed to the pipeline in the shelf, Control the shelf temperature so that the shelf cools to a predetermined temperature and freezes. Temperature control system for shelves in the freeze drier, characterized in Rukoto.

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