Patent Application
20070022622
The present invention relates to freeze drying apparatus.
Freeze drying is a process that removes water from a sample by sublimation of frozen water. Freeze drying is particularly useful in the pharmaceutical industry, as the integrity of the samples is preserved during the freeze drying process and sample stability can be guaranteed over relatively long periods of time.
One known type of freeze drying apparatus for producing pharmaceutical tablets comprises a freezing apparatus for receiving a sheet, tray or blister pack having a number of depressions each containing a liquid pharmaceutical sample to be freeze dried, and for refrigerating the blister pack to freeze the samples, for example, by exposing the samples to liquid nitrogen or liquid carbon dioxide. The sheet is then conveyed from the freezing apparatus to a drying chamber. The drying chamber usually includes a number of heating shelves, each of which could be raised and lowered within the chamber relative to a loading position at which the sheet can be loaded on to the shelf. Access to the chamber for automated loading and removal of the sheet is generally through an opening formed in a wall or in the main door of the chamber. Fixed shelves with manual loading or alternative loading systems are also adopted.
In the drying process, the temperature of the drying chamber is initially reduced to a temperature below the samples freezing temperature so that the water within the samples remains frozen during loading of the chamber. Following loading, the opening to the chamber is closed. The chamber is evacuated to a pressure typically below 1 mbar, and the shelves are heated to cause the ice within the samples to sublimate into water vapour. A duct connected to the drying chamber conveys the water vapour to a condensation chamber containing a cold condenser. Ice condensed within the condenser chamber can be removed at a later stage. The driving force for the water vapour transport is the pressure difference between the drying chamber and the condensation chamber. This pressure difference is caused by the fact that the condensation chamber is maintained at a lower temperature than the samples. A vacuum pump is usually provided downstream from the condensation chamber to serve as a facilitating element for the transport of water vapour from the drying chamber to the condensation chamber, in terms of minimising the ‘mean free path length’.
Following the completion of the drying process, the drying chamber is pressurised back to atmospheric pressure, and the sheet, now containing solid pharmaceutical tablets, is then unloaded from the drying chamber, and transferred to a packaging station, for example, for removal of the tablets from the depressions for bottling, or by sealing of the depressions by application of a film to the sheet to enclose the tablets.
An important issue in the use of such freeze drying apparatus is that the water within the samples should remain in a frozen state as the sheet is transferred from the freezing apparatus to the drying chamber. For this purpose, the sheet is typically transferred from the freezing apparatus into a first, refrigerated transfer vehicle. The first transfer vehicle is then moved to a position adjacent the opening of the drying chamber, and from which the sheet is loaded into the drying chamber. Once the drying of the samples has been completed, the sheet is transferred to a second transfer vehicle, which is then moved to the packaging station. However, due to the exposure of the samples to the ambient atmosphere as they are transferred from the first transfer vehicle to the drying chamber, there is a risk that some of the ice within the samples may melt, thereby reducing the efficiency of the subsequent drying process.
It is an aim of at least the preferred embodiment of the present invention to seek to solve these and other problems.
In a first aspect, the present invention provides freeze drying apparatus comprising a mobile drying chamber for receiving samples, and a condenser, wherein the drying chamber is moveable between a first location at which samples are loaded thereinto, and a second location at which the chamber is connected to the condenser.
In a second aspect, the present invention provides freeze drying apparatus comprising freezing apparatus for freezing a liquid component of a sample into a solid, a mobile drying chamber for receiving samples from the freezing apparatus, a condenser, a condenser conduit system for conveying vapour from the drying chamber to the condenser, the condenser conduit system comprising an inlet for connection to the drying chamber, and an isolation valve for selectively isolating the inlet from the condenser, an evacuation system for evacuating the drying chamber; and a thermal control system for controlling the temperature of the samples located within the drying chamber; wherein the drying chamber is moveable between a first location at which samples are transferred from the freezing apparatus to the chamber, and a second location at which the chamber is connected to the inlet of the condenser conduit system.
By conducting the drying of the samples, for example pharmaceutical samples such as tablets, within a mobile drying chamber that receives frozen samples from the freezing apparatus, the risk of any ice melting within the samples can be significantly reduced, as the step of transferring the samples from the mobile chamber to a conventional drying apparatus is eliminated. With the conventional drying chamber and second transport vehicle for transporting samples from the conventional drying chamber therefore being no longer required, the number of components of the freeze drying apparatus can also be reduced in comparison to the prior art apparatus.
The mobile drying chamber may be manually moved between locations, for example by providing the drying chamber with wheels to enable an operator to push the drying chamber between locations. Alternatively, the mobile drying chamber may be moved between locations by an automated guided vehicle (AGV) system. Following the completion of the drying process, the drying chamber can be disconnected from the condenser and moved to a third location at which the samples are unloaded from the drying chamber for packaging, for example, either individually or in bottles.
In a preferred embodiment, the evacuation system is configured to evacuate the drying chamber via the inlet of the condenser conduit system, and preferably through the condenser, thereby minimising the number of connections that need to be made to the drying chamber at the second location.
A drying chamber pre-evacuation system is preferably provided for at least partially evacuating the drying chamber before the drying chamber is connected to the evacuation system. This can enable the drying chamber to be pre-evacuated to the operating pressure of the condensation conduit system and condenser before the isolation valve is opened to expose the drying chamber to the evacuation system. The pre-evacuation system preferably comprises a vacuum pump, and a vacuum conduit system comprising an inlet connected to the condenser conduit system, an outlet connected to the vacuum pump, and an isolation valve for selectively isolating the inlet of the vacuum conduit system from the outlet of the vacuum conduit system. As a result, the number of connections that need to be made to the drying chamber at the second location may be minimised.
The thermal control system preferably comprises heating apparatus for heating the samples located within the drying chamber to cause the solid to sublime into vapour and/or to complete the drying process. The drying chamber may be provided with an integral heating apparatus, for example, to heat shelves upon which the samples are located within the chamber. Alternatively, the drying chamber may be connected to external heating apparatus at the second location. The external heating apparatus may comprise a source of a heated fluid, such as one of silicone oil and a mixture of water and glycol, and means for selectively conveying the heated fluid to the drying chamber to increase the temperature of the samples therein.
The mobile drying chamber may be thermally insulated to maintain the liquid component of the frozen sample in solid form until drying of the sample is to be commenced. Alternatively, or additionally, the thermal control system may comprise cooling apparatus for maintaining the liquid component of the frozen samples located within the drying chamber as a solid. The drying chamber may be provided with an integral cooling apparatus, for example, to cool the shelves upon which the samples are located within the chamber. Alternatively, the thermal control apparatus may be an external apparatus connectable to the drying chamber at the first location so that the liquid component of the samples remains frozen as the samples are transferred from the freezing apparatus into the drying chamber, and/or at the second location so that the liquid component of the samples remains frozen until the drying process is commenced. The external cooling apparatus may comprise a source of a coolant, and means for selectively conveying the coolant to the drying chamber.
An isolation valve may be provided for selectively isolating the condenser from the condenser conduit system. In order to provide redundancy to enable the condenser to be periodically serviced by defrosting, emptying of liquid and cleaning, the apparatus may comprise an additional condenser, and an additional isolation valve for selectively isolating the additional condenser from the condenser conduit system. This enables one of the condensers to receive the vapour from the drying chamber while the other is being serviced, thereby enabling servicing to be performed without interrupting use of the freeze drying apparatus.
In a preferred embodiment, the drying chamber has an opening through which the samples are transferred into the chamber from the freezing apparatus, and a door for closing the opening, the door having a slot formed therein for exposing part of the opening, and wherein the freeze drying apparatus comprises means for moving the door in a direction transverse to the opening. The moving means preferably comprises means for raising and lowering the door. In order to expose only a limited number of shelves within the drying chamber when samples are transferred to the chamber, the drying chamber preferably comprises a flexible screen attached to one end of the door, and a reel located beneath the opening and from which the flexible screen is unwound as the door is raised. This screen serves to reduce heat loss from the chamber as the end of the door is raised above the bottom edge of the opening of the chamber.
The moving means is preferably located at the second location, and preferably comprises means for releasably engaging the door.
Additional mobile chambers may be provided to permit the use of the freeze-drying apparatus to be substantially continuous. For example, while one chamber is being loaded with samples at the first location, other chambers may be located at the second location for drying the frozen samples, located at the third position for unloading of the dried samples, being cleaned, and/or being cooled in readiness for receiving samples from the freezing apparatus.
The conduit system may be configured to have a plurality of inlets each being selectively connectable to a respective drying chamber thereby to enable a plurality of drying chambers to be connected to the condensation chamber for drying. In this case, a plurality of isolation valves are preferably provided, each for selectively isolating a respective inlet from the outlet, with the drying chamber evacuation system being configured to evacuate each of the drying chambers at the second location.
A vacuum pump may be provided for each drying chamber to enable the pressure within a drying chamber to be reduced to the pressure within the condenser conduit system before the respective isolation valve is opened to operatively connect that drying chamber to the condenser. Alternatively, a pre-evacuation system may comprise a vacuum pump, and a vacuum conduit system comprising a plurality of inlets each connected to the condenser conduit system between a respective inlet of the condenser conduit system and a respective isolation valve of the condenser conduit system, an outlet connected to the vacuum pump, and a plurality of isolation valves each for selectively isolating a respective inlet of the vacuum conduit system from the outlet of the vacuum conduit system. By providing a common vacuum pump for evacuating each of the mobile chambers at the second location, costs can be reduced.
In a third aspect, the present invention provides freeze drying apparatus comprising freezing apparatus for freezing a liquid component of a sample into a solid, a plurality of mobile drying chambers for receiving samples from the freezing apparatus; a condenser, a condenser conduit system comprising a plurality of inlets each being selectively connectable to a respective drying chamber, and a plurality of isolation valves each for selectively isolating a respective inlet from the condenser; an evacuation system for evacuating the drying chambers; and a thermal control system for controlling the temperature of the samples located within the drying chambers; wherein each drying chamber is moveable between a first location at which samples are transferred from the freezing apparatus to the chamber, and a second location at which the chamber is connected to an inlet of the condenser conduit system.
In a fourth aspect the present invention provides freeze drying apparatus comprising a drying chamber having an opening formed therein for providing access to the chamber and a door for closing the opening, the door having a slot formed therein; and means for raising the door in a direction transverse to the opening so that the slot exposes part of the opening to permit samples to be loaded into the chamber; the drying chamber comprising a flexible screen attached to a bottom end of the door and a reel located beneath the opening and from which the flexible screen is unwound as the door is raised.
Preferred features of the present invention will now be described with reference to the accompanying drawing, in which
FIGS. 2(a) and 2(b) are side and front views respectively of a mobile drying chamber of the apparatus of
FIGS. 5(a) and (b) illustrate the connection of the drying chamber to the inlet of the condenser conduit system of the apparatus of
With reference first to
An automated manipulator (not shown) is located at the outlet 14 of the freezing apparatus 12 for transferring frozen samples from the freezing apparatus 12 into one or more mobile drying chambers 16 located at a first, loading location, indicated generally by arrow 18 in
With reference to
Each drying chamber 16 is loaded through an opening 20 formed in one side of the chamber 16. The drying chamber 16 comprises a door 22 for closing the opening 20 to isolate the shelves 19 from the external environment. FIGS. 2(a) and 2(b) illustrate the door 22 in a lowered, closed position in which the door 22 is positioned adjacent the opening 20. One or more seals 24 may be located about the opening 20 to form an air-tight seal with the door 22.
To enable the frozen samples to be loaded into the drying chamber 16, the door 22 is raised to expose one or more shelves 19 of the drying chamber 16 at any given time. A mechanism 26 for raising and lowering the door 22 relative to the drying chamber 16 is located at the loading location 18. The moving mechanism 26 comprises an arm 28 having a latch 32 located at the lower end thereof for releasably engaging a catch 30 connected to the upper end of the door 22. A drive motor 34 is connected to the arm 28 to enable the latch 32 to be selectively raised and lowered, and thereby raise and lower the door 22.
In order to maintain the liquid component of the samples loaded into the drying chamber 16 as a solid until the drying process is started, the shelves 19 are chilled prior to the loading of the samples into the drying chamber 16. Returning to
Returning to
In order to minimise heating of the drying chamber 16 as the door 22 is raised to expose the shelves 19, the drying chamber 16 comprises a flexible screen 50 attached to the lower end of the door 22, and a reel 52 located beneath the opening 20 and from which the flexible screen 50 is unwound as the door 22 is raised. As illustrated in
Once the uppermost shelf has been loaded, the motor 34 is reversed to lower the door 22 to the closed position illustrated in FIGS. 2(a) and 2(b). The valves 46 are closed, and the drying chamber 16 is disconnected from the thermal control system 36. The drying chamber 16 may be thermally insulated to maintain the liquid component of the frozen samples within the drying chamber 16 in solid form until drying of the samples is to be commenced. The drying chamber 16 is then moved from the loading location 18 to a second, drying location, indicated generally at 60 in
As illustrated in
In addition to the first branch conduits 72, a plurality of sets of second branch conduits 76 are also provided at the drying location 60, each set branching off from the coolant conduit system 40 and being connected to a respective set of first branch conduits 72 to convey coolant to the drying chamber 16 at the drying location 60.
The supply of coolant to and from the drying chamber 16 is controlled using valves 78 provided within the second branch conduits 76. Initially, valves 74 and 78 are closed. When the ports 64 of the drying chamber have been connected to the thermal control system 36, valves 78 are opened to supply coolant to the drying chamber, and thus maintain the liquid component of the samples located within the drying chamber 16 as a solid until the start of the drying process.
With reference to
The vapour outlet 88 may be connected to inlet 86 of the condenser conduit system 82 may any suitable means. For example, as illustrated in
Returning to
Prior to the connection of the drying chamber 16 to an inlet 86 of the condenser conduit system 82, the isolation valve 90 is closed to prevent ingress of air into the condensation chamber 80. In order to prevent a process disturbance when the isolation valve 90 is opened following connection of the drying chamber 16 to the inlet 86, the drying chamber 16 is preferably pre-evacuated to reduce the pressure within the drying chamber 16 to a pressure similar to that within the condensation chamber 80 and condenser conduit system 82 before the isolation valve 90 is opened.
For pre-evacuating the drying chambers 16, the freeze drying apparatus 10 further comprises a drying chamber pre-evacuation system 104. In the illustrated embodiment, the pre-evacuation system 104 comprises at least one vacuum pump 106 for pre-evacuating each of the drying chambers 16 connected to the condenser conduit system 82. The vacuum pump(s) 106 are connected to an outlet 108 of a manifold 110 of a vacuum conduit system 112. The manifold 110 has a plurality of inlets 114, each inlet 114 being connected to the condenser conduit system 82 between a respective flanged inlet 86 and associated isolation valve 90. The vacuum conduit system 112 further includes a plurality of isolation valves 116, each isolation valve 116 being located between the manifold 110 and a respective inlet 114.
The isolation valves 116 are normally in a closed position to isolate the inlet 86 of the condenser conduit system 82 from the pre-evacuation system 104. Following connection of the drying chamber 16 to an inlet 86 of the condenser conduit system 82, and with the associated isolation valve 90 remaining closed, the isolation valve 116 is opened to enable air to be drawn from the drying chamber 16 by the pre-evacuation system 10. Once the pressure in the drying chamber 16 has been reduced to a pressure similar to that created in the condenser conduit system 82 by the evacuation system 100, the isolation valve 116 is closed and the appropriate isolation valve 90 of the condenser conduit system 82 is opened to expose the drying chamber 16 to the condenser 102 and the evacuation system 100 to start the drying process. The supply of coolant to the drying chamber 16 is stopped, by closing the appropriate valves 78, and the supply of heated fluid to the drying chamber is started, by opening the appropriate valves 74, to heat the frozen samples located within the drying chamber 16 to cause the solid with the samples to sublime into vapour. The vapour is drawn from the drying chamber 16 by the evacuation system 100, the vapour passing through the condenser conduit system 82 to the condensation chamber 80, wherein the vapour condenses on the surface of the condenser 102.
As illustrated in
The drying process is continued until all of the vapour has been emitted from the samples. A pressure rise within the drying chamber 16 may be used to determine the end of the drying process. Once the drying process has been completed, the isolation valve 90 is closed to isolate the drying chamber 16, and the pressure within the drying chamber 16 is gradually returned to atmospheric pressure using an air admittance system 132 illustrated in
Once the drying chamber 16 has been unloaded, the AGV system moves the drying chamber to a fourth, washing location, indicated at 138 in
While the foregoing description and drawings represent the preferred embodiments of the present invention, it will be apparent to those skilled in the art that various changes and modifications may be made therein without departing from the true spirit and scope of the present invention.
