Classifications

• • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
  • F26—DRYING
  • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
  • F26B5/00—Drying solid materials or objects by processes not involving the application of heat
  • F26B5/04—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum
  • F26B5/06—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing

Definitions

• the invention relates to a freeze-drying chamber with coolable / heatable shelves for a large number of product-filled containers or with coolable heatable shelves which can be covered with product layers, with special devices which eliminate the harmful temperature effects of the chamber wall surfaces which depend on the progress of drying. Special designs make it possible to avoid high energy loss through a special chamber wall structure while reducing the mass of the temperature-controlled components
• the avoidance of inhomogeneity is achieved by eliminating the driving potential responsible for the irregularities.
• the driving potential for drying is the temperature difference between product-filled containers or product layers and their surroundings, which provides the potential necessary for freeze-drying to proceed. This potential is greater in the edge area of the shelves than in the middle area of the shelf because direct heat exchange by radiation and convection takes place between containers on the edge and the chamber wall.
• the natural convection of the gas acts in the free gap between the wall and the temperature-controlled one
• Plates particularly strong as a heat transfer medium for the convection current exposed container are particularly strong as a heat transfer medium for the convection current exposed container. These additional heat flows decrease towards the middle of the plate and thus cause the inhomogeneous freezing and drying process of the containers or product layers distributed over the plate.
• freeze dryers are manufactured either without a temperature control device for the chamber walls or with heating / cooling jackets that are applied directly to the supporting structure.
• These heating / cooling jackets have the purpose of cooling the chamber from the sterilization temperature to the temperature suitable for loading because of the short to ground with the heavy supporting structure of the chamber. Thereafter, the coolant is usually emptied from these heating / cooling surfaces in order to reduce mass.
• the cooling of the chamber wall to a temperature that eliminates the driving potential responsible for the fault is not possible with these designs.
• the additional cooling surfaces are in the mechanical support structure of the
• Integrated dryer which must be sufficiently reinforced for evacuation. This has the disadvantage of having to heat / cool large masses during operation of the dryer. Therefore, the dryer necessarily reacts thermally slow.
• Containers leads to uneven temperature and drying profiles of the containers
• the unevenness is eliminated by regulated heating / cooling plates, which are set so that there is no driving temperature gradient between the wall and the containers.
• the homogeneity of the freezing and drying process of all containers enables the uniformity of the product quality to be improved and the drying capacity to be increased considerably.
• the driving potential responsible for the fault is eliminated by means of additional temperature-controlled heating / cooling surfaces which are introduced into the drying chamber. These heating / cooling surfaces can be arranged differently. Remaining natural convection - as e.g. between containers or product layers and shelves - is minimized by additional pressure reduction during the freeze section of freeze drying.
• the invention relates to a drying apparatus for removing solvent from moist material, consisting of at least one drying chamber with at least one positioning plate for receiving containers or flat layers of moist material filled with moist material, the drying chamber being connected to a condenser via a vapor channel which the sublimed solvent can be separated off, the setting plates being connected to a temperature-controlled heating / cooling circuit, the chamber having heating / cooling plates or which are connected to a second heat transfer circuit, characterized in that that the heating / cooling plates are largely thermally decoupled from the chamber wall.
• the shelves can be used with a
• Piping system should be provided.
• a current of temperature-controlled heat transfer medium flows through the piping system, which is supplied from a heating / cooling system.
• a preferred drying apparatus is characterized in that the heating / cooling plates are arranged or spaced from the chamber wall.
• the outer chamber wall is particularly preferably designed to be pressure-resistant, so that the surface forces are absorbed without deformation when the chamber is evacuated.
• a drying apparatus is also preferred in which the outer chamber wall has thermal insulation so that the energy loss of the system is minimized.
• the heating / cooling surfaces are connected in particular via spacers with the inner surface of the chamber wall mechanically 'and form therewith an evacuable flat gap.
• vacuum connections are provided in the chamber wall.
• a drying apparatus is also preferred, characterized in that the gap can be adjusted to the pressure level of the drying chamber by a vacuum system for the purpose of pressure equalization.
• the spacers are preferably made of poorly heat-conducting material, in particular stainless steel.
• a special version of the drying apparatus is characterized in that elastic connecting plates between the side heating / cooling plates and the
• Chamber wall must be designed so flexibly that the temperature-related changes in length of the heating / cooling surfaces can be compensated for without material damage.
• Heating / cooling plates are hung parallel to the edges of the positioning plates at a distance from the positioning plates in the drying chamber, so that the hanging heating / cooling plates form an almost closed radiation cage around the stack of positioning plates
• the drying chamber is already evacuated during the freezing process in order to reduce the effects of convection
• the chamber wall has external thermal insulation.
• the facilities for CLP / SIP are installed in such a way that all surfaces can be cleaned.
• a drying apparatus is preferred, characterized in that the temperature control systems for the heating / cooling plates can be set to the suitable temperature in a sensor-controlled manner.
• the temperature control systems for the heating / cooling plates are predictively controlled to the appropriate temperature by a computer program.
• the temperature control systems for the heating / cooling plates are made up of a hybrid system consisting of sensor and
• the same mass ratios between the heating / cooling plates and the setting plates are produced, thus enabling approximately the same temperature / time profiles for walls and setting plates / containers.
• the container and the shelf are not at the same temperature during the first drying section, so that a mixed temperature of the container and the shelf temperature must be set for the wall temperature.
• This mixing temperature is expediently determined with the aid of a simulation program on the basis of a predefined lyocycle (temperature, pressure and time profile).
• the solution to this problem is achieved by installing the separately temperature-controlled heating / cooling surfaces that surround the shelves on all four sides, so that an almost closed radiation cage is created.
• the regulation / control of the heating / cooling plate temperature can be carried out according to the following strategies:
• Heating / cooling plates regulated according to the same temperature program After starting the drying program, the heating / cooling plate temperature and the shelf temperature follow different programs.
• the shelf temperature is determined by the specified lyocycle and the temperature / time program specified in the lyocycle is run and regulated.
• the temperature of the heating-Z cooling plates is set in the first drying section to the sublimation temperature of the frozen product, which is dependent on the chamber pressure and on the solvent. In a first approximation, this temperature can be calculated on the basis of the material values. Measurements of the sublimation temperature in the laboratory can be used to correct this calculated temperature.
• the pressure increase method for the direct determination of the sublimation temperature can also be used, e.g. by G.W. Oetjen in "Freeze drying", VCH Verlag, 1997 is described.
• the temperature of the heating / cooling plates must be changed when the second
• Dry section begins.
• the beginning of the second drying section can be detected are measured by measuring the system pressure in the gas flow from the freezer with different pressure measuring probes, e.g. an absolute pressure measuring device and a conductivity probe (e.g. Pirani probe), which is set to nitrogen. If the solvent vapor flow approaches 0 at the end of the first drying section, both measured values approach the same value because the nitrogen content in the
• the temperature of the heating / cooling plates can now be slowly increased to the temperature of the shelf and adjusted as the drying of the shelf temperature continues.
• the degree of approximation to the shelf temperature is e.g. determined as a function of the pressure difference between the two pressure displays.
• freeze-drying properties / parameters of the product have been used, if the freeze-drying properties of the freeze dryer are known, the drying process of the product can be calculated in advance and the values of the product temperature determined by the calculation program can be used as a guide for the heating / cooling plate temperatures. This method is shown in Fig. 3b.
• Hybrid method Here the product temperatures are determined from the measurements in the freeze dryer (absolute pressure, pressure after conductivity probe) and simulation calculations and used as a guide for the heating / cooling plate temperature.
• the invention also relates to a method for drying moist material using a drying apparatus according to the invention, with the steps: sterilizing, optionally hot sterilizing the chamber including the unoccupied setting plates,
• Figure 1 shows the typical structure of a freeze-drying chamber according to the invention with a condenser, setting plates and wall-integrated heating / cooling plates, which are connected to a separately controllable heating / cooling circuit and whose space between mechanically rigid, heavy wall structure and heating / cooling plates can be evacuated.
• Fig. La shows a horizontal section through the freeze-drying chamber of Figure 1 with wall-integrated heating / cooling plates.
• FIG. 2 shows a variant of the freeze-drying chamber according to the invention with heating / cooling plates which are hung vertically in front of the stack of storage plates and are connected to a separately controllable heating / cooling circuit;
• 3a shows the temperature profile of containers which are at the edge or in the middle of the positioning plate with an unregulated wall temperature
• 3b shows the temperature profile of the containers, which stand at the edge of the plate or in the middle of the positioning plate, with the wall temperature regulated according to the invention
• 3c shows the temperature profile of the containers which are at the edge of the plate or in the middle of the positioning plate when the wall temperature is regulated in accordance with US Pat. No. 5,398,426;
• FIG. 1 shows a system of freeze-drying chamber 1 and condenser chamber 22, in which containers of product-filled containers are frozen and freeze-dried.
• Fig. La container 3 on the shelf 2 in edge and
• the chamber 1 has two doors 11, 11a which can be opened separately and which are tightly closed.
• the freeze-drying chamber 1 has a two-shell structure.
• the heavy chamber wall construction 6 with reinforcing ribs 7 has the task of a vacuum-tight, torsionally rigid, which withstands the atmospheric pressure when the freeze-drying chamber 1 is evacuated
• the chamber 1 is equipped with thermal insulation material 8 on its outside to prevent heat exchange with the environment.
• the inner freeze-drying chamber 23 is formed from the heating-cooling plates 4, which are kept at a distance from the chamber wall 6 with the aid of spacers 5, are connected in a pressure-tight manner to the chamber wall 6 via flexible sheets 9, so that the intermediate space 24 between heating / cooling plates 4 and Support wall 6 of the chamber 1 can be evacuated.
• the evacuation takes place via pipes 10, 12 which are connected to the main vacuum pump 21 via valves 20.
• the evacuation of the intermediate space 24 serves two purposes: First, the pressure equalization between the freeze-drying chamber 23 and the space 24 between the heating / cooling plates 4 and the chamber wall 6, so that pressure forces on the heating / cooling plates 4 are avoided. Secondly, it serves to lower the> heat exchanger by reducing the effective heat conduction of the intermediate space 24 as a function of pressure.
• the pressure in the intermediate space 24 is the same as in the freeze-drying chamber 23 (p ⁇ 0.1 mbar), so that the intermediate space 24 is the same evacuated gap of a dewar acts.
• the spacers 5 between the heating / cooling plates 4 and the chamber wall 6 are made of a poorly heat-conducting material (e.g. stainless steel), and the number of spacers 5 is minimized to the extent necessary so that the heat transfer by heat conduction through the
• the connecting plates 9 are designed so that the temperature-dependent change in length of the heating / cooling plates 4 can be absorbed by the plates without any risk to the mechanical strength of the connection to the chamber wall 6. In this way, a smooth-surface freeze-drying chamber 23 is created, which can be easily cleaned.
• the heating / cooling plates 4 are supplied with heat transfer fluid (silicone oil) via a separately controllable temperature control system (not shown), which is supplied via line 13 and discharged via line 14.
• the temperature control system uses the same heat transfer medium as the shelves and can be supplied from the same storage container.
• the temperature control system for the heating / cooling plates 4 must always be operated at a temperature matched to the vial temperature, while the heat transfer medium for the setting plates 2 follows a different temperature program that follows the Lyo cycle.
• the temperature program for the heating / cooling plates 4 depends on the temperature of the containers. This method has already been described in general terms above.
• FIG. 2 shows another embodiment of the freeze dryer with regard to the attachment of heating / cooling plates 4 '.
• the temperature-controlled plates 4 ' hang freely in the chamber 23.
• the heating / cooling plates 4' are suspended at a distance parallel to the edges of the positioning plates 2, so that space for all the organs assigned to the positioning plates 2, e.g. Hoses 25, 26 for the heat transfer medium, shelf holder (not shown), is preserved.
• Known ClP / Sff devices can also be provided in the interior of the chamber.
• the heating / cooling plates 4 ′ are in turn fed by the heat transfer medium from a separate heat transfer circuit via inlet 13 and return 14.
• the mass the heating / cooling plates corresponds in both embodiments (according to example 1 and 2) to the mass of the setting plates 2, so that the heating / cooling dynamics of the plates 2 and 4 or 4 'are coordinated with one another and there are no temperature shifts due to mass inequality.
• Fig. 3a shows the temperature profile of the container, the edge or in the middle of the
• indices 1 stand for the temperature at 1 mm cake height of the drying goods and indices 6 for the temperature at 6 mm cake height of the drying goods;
• 3b shows the temperature profile of the containers, which stand at the edge of the plate or in the middle of the positioning plate, with the wall temperature regulated according to the invention;
• the abbreviations denote: a regulated wall temperature b shelf temperature c edge container temperature d center container temperature;
• 3c shows the temperature profile of the containers which are at the edge of the plate or in the middle of the positioning plate when the wall temperature is regulated in accordance with US Pat. No. 5,398,426;
• the abbreviations denote: a regulated wall temperature b shelf temperature c edge container temperature d center container temperature.
• FIG. 4 shows the data from an experiment in a 1 m 2 pilot freeze dryer (I m 2 footprint). All thin lines are measured values. The bold lines are calculated values. The temperature profiles of containers 3 that stand at the edge of the plate and the temperature profiles of containers 3 that were arranged in the center of the plate - far from the wall and protected by the neighboring containers - were compared. The calculated temperature profiles distinguish two cases:
• the wall itself is in heat exchange with the setting plates 2 and the surroundings and is therefore taken into account as changing over time.
• the match of calculated temperatures with the measured temperatures can be considered satisfactory if one takes into account the difficulties of measuring the temperature in the containers. From this measurement and the evaluation by the simulation program it can be deduced that the marginal containers 3 will also follow the temperature profile of the containers in the center when eliminating the driving temperature potential between the wall and the setting plates 2, as is the case in the diagram in FIG. 3b for another case was calculated; In Fig.
• abbreviations a to g mean: a shelf temperature b calculated wall temperature bj 23 measured wall temperatures c chamber pressure (measured) d central container temperature (measured) e central container temperature (calculated) f edge container temperature (measured) g edge container temperature (calculated).

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• Engineering & Computer Science (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Molecular Biology (AREA)
• Mechanical Engineering (AREA)
• General Engineering & Computer Science (AREA)
• Drying Of Solid Materials (AREA)
• Apparatus For Disinfection Or Sterilisation (AREA)
• Paper (AREA)
• Seal Device For Vehicle (AREA)

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