EP3093597B1 - Installation de lyophilisation - Google Patents

Installation de lyophilisation Download PDF

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Publication number
EP3093597B1
EP3093597B1 EP15167172.4A EP15167172A EP3093597B1 EP 3093597 B1 EP3093597 B1 EP 3093597B1 EP 15167172 A EP15167172 A EP 15167172A EP 3093597 B1 EP3093597 B1 EP 3093597B1
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EP
European Patent Office
Prior art keywords
ice
chamber
gas
product
supply
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EP15167172.4A
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German (de)
English (en)
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EP3093597A1 (fr
Inventor
Michael Umbach
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MARTIN CHRIST GEFRIERTROCKNUNGSANLAGEN GmbH
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MARTIN CHRIST GEFRIERTROCKNUNGSANLAGEN GmbH
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Priority to EP15167172.4A priority Critical patent/EP3093597B1/fr
Priority to PCT/EP2016/055439 priority patent/WO2016180558A1/fr
Publication of EP3093597A1 publication Critical patent/EP3093597A1/fr
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    • 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 plant. Furthermore, the invention relates to a method for controlling a freeze-drying plant.
  • Freeze drying systems are used for the gentle drying of a high-quality material to be dried, in particular a pharmaceutical or biochemical drying material.
  • the material to be dried contains a solvent (or any liquid) which is to be removed by freeze-drying.
  • a drying material is freeze-dried in containers, which are preferably formed in the context of the present application as so-called vials.
  • Vials are formed with a container and a lid or plug (hereinafter "lid").
  • the lid is partially open during the freeze-drying process so that it does not seal the container in a fluid-tight manner (ie, not liquid-tight or non-gastight) and sublimated solvent can escape from inside the vial during the freeze-drying process. If, at the end of the freeze-drying process, the solvent is removed (as far as possible) from the material to be dried and the vials, the lid is completely closed in order to produce a fluid-tight seal.
  • the drying material in the vials is first frozen in a product chamber of the freeze-dryer.
  • a so-called primary drying is carried out by sublimated in the product chamber at low pressure or technical vacuum and low temperature, the solvent contained in the Trocknungsgut without intermediate occurrence of a liquid phase directly from the frozen state to the gaseous state.
  • the previously sublimated solvent precipitates as ice.
  • Secondary drying may be followed by the primary drying described, in which more strongly bound solvent is removed by heating the material to be dried and reducing the pressure.
  • the vials in the product chamber remains the final product of freeze-drying, which is referred to as lyophilisate.
  • the drying stock does not freeze with a drop below freezing temperature in all vials at the same time, but rather within a period of time that may be in the range of minutes or hours.
  • the time-delayed formation of nuclei for the formation of ice crystals in the area of dissolved particles, in the range of roughness or defects of the inner surface of the vial u. ⁇ .
  • Supercooling is understood as meaning a further lowering of the temperature below the freezing temperature (for example, up to more than 30 K below the freezing temperature), without directly leading to the formation of a solid phase. Formed ice crystals are stable only from a minimum size, with the minimum size decreasing with the extent of underrun of the freezing temperature. Subsequent to formation of ice crystal seeds, crystal growth results until finally the entire product is frozen. Finally, the amount of time within which all vials are frozen can be reduced with the extent of supercooling. Depending on the extent of falling below the freezing temperature but results in a frozen Trocknungsgut with different geometry of the ice crystals. Depending on the number of dissolved particles, a randomly distributed different nucleation and ice crystal growth behavior may also result in the vials.
  • the aim is to achieve as homogeneous a process design as possible for all vials, in particular with a freezing of the drying material in all vials at the same time and with the formation of ice crystals of comparable shape and size in all vials.
  • a standardization of the entry of the freezing of the drying material in the vials by additives is undesirable because they can affect the purity of the lyophilisate.
  • Other well-known measures to standardize the occurrence of freezing of the drying material In the vials for example, there is an ultrasonic excitation or generation of mechanical vibrations or acoustic waves, with which the formation of crystal nuclei is to be standardized.
  • electric fields have been used to standardize the freezing process.
  • WO 2011/034980 A1 It is proposed to introduce liquid nitrogen via a Venturi injector in the product chamber.
  • the Venturi injector moist air from the drying chamber is converted into ice crystal mist by means of the liquid nitrogen, which then acts on the vials.
  • the Venturi injector acts as a kind of pump for the moist air and the ice mist, wherein a closed circuit from the Venturi injector via the vials to a the individual shelves for the vials associated branched return device is formed. It is possible a simultaneous or temporal subsequent pressurization of the product chamber. By means of the pressurization is to be additionally caused that ice crystals enter the vials.
  • a pressurization can take place here by supplying the liquid nitrogen under pressure with simultaneous closure of an outlet port of the drying chamber. Furthermore, it is suggested that the pressurization be enhanced by creating a vacuum in the product chamber by means of a vacuum pump prior to loading the vials with the ice crystal mist. Finally, it is also proposed to bring about a pressure reduction after the introduction of the ice-crystal mist, with which the freezing process should be further supported.
  • the publication WO 2010/117508 A2 discloses a freeze dryer in which a product chamber via a pressurizing circuit from a gas supply, here a pressure vessel, sometimes under gas pressure can be applied.
  • the control of the application of the gas via a control valve, which can be controlled by an electronic control unit.
  • the gas can optionally be cooled or heated before being fed to the product chamber.
  • the product chamber is pressurized with an inert gas such as argon, nitrogen or air.
  • an inert gas such as argon, nitrogen or air.
  • the pressure in the product chamber can be increased to about 4.5 bar at about -1 ° C to -10 ° C. This condition is maintained for about 15 minutes, with the Drying material is at or near the nucleation temperature for ice crystals.
  • a vacuum within the product chamber is brought about within 0.5 to 20 seconds by operation of a vent circuit, which then the increased nucleation is to take place.
  • a further cooling of the product chamber and the vials to about -40 ° C to -45 ° C take place.
  • the freezing process is based on the very rapid pressure reduction in the product chamber. Due to the pressurization of the product chamber with high pressures, this method can not be used for all types of freeze-drying plants. Furthermore, large cross-sections are required for the connections, which increases the cost and space requirements. Escaping gases may not get into the atmosphere, for example, toxic drying material, so that a u. U. also large-sized collecting tank is required, which further increases the cost and space.
  • the publication WO 2012/148372 A1 proposes to produce an ice mist in an ice condenser chamber of a freeze dryer, wherein the pressure of the ice mist in the ice condenser chamber is greater than the pressure in the product chamber.
  • the product chamber has a temperature of about -5 ° C, while the temperature in the ice condenser chamber in the range of -53 ° C to -85 ° C.
  • the atmospheric pressure prevails in the ice condenser chamber, while in the product chamber a vacuum (for example 65 mbar) prevails.
  • the ice condenser chamber is specifically supplied with a filling gas provided with moisture.
  • a disadvantage may be the need to supply the filling gas, which is a foreign medium.
  • any additional required ice condenser chamber increases the cost and space requirements.
  • a freeze-drying plant which has a product chamber.
  • Products in the product chamber go through the freeze-drying process.
  • the products are vials with disposed therein Trocknungsgut.
  • the product chamber has a plurality of superposed shelves on which a plurality of vials can be arranged.
  • the freeze-drying plant according to the invention has an ice chamber.
  • ice crystals are available and / or produced.
  • the preparation can be done in any way.
  • the ice crystals are generated from solvent which has previously been evaporated from the drying stock in the vials and which has passed into the ice chamber where the ice crystals are then formed.
  • the ice crystals are made from otherwise supplied liquid, in particular a liquid container arranged in the product chamber or the ice chamber, or via an external liquid connection.
  • the storage of the ice crystals can then take place in any desired manner, in particular in the form of an ice mist and / or in the form of deposits of the ice crystals on cooled surfaces or a cooling coil.
  • any gas can be used, in particular an inert gas such as, for example, nitrogen or argon.
  • the supply, the valve, the ice chamber and the product chamber are arranged one behind the other in this order.
  • the freeze-drying system has a control unit, by means of which a control signal can be generated, which opens the aforementioned valve.
  • the opening of the valve occurs in the cumulative presence of the following conditions: First, in the ice chamber ice crystals must be present. On the other hand, at the time of opening the valve, the ice chamber must be connected to the product chamber via an opening.
  • the opening between the ice chamber and the product chamber can permanently exist via a permanent crossover cross section.
  • the ice chamber and the product chamber may be formed as an integral chamber. It is quite possible, however, that at the time of opening of the valve by the control unit through the opening, the ice chamber and the product chamber are interconnected, while in another phase of the freeze-drying plant, especially in an operating phase, in which neither the generation of ice crystals in the ice chamber, the freezing of the material to be dried in the product chamber and / or the primary drying takes place, the opening is partially or completely closed by a valve device.
  • the opening of the valve by the control signal of the control unit in view of the pressure conditions mentioned has the consequence that gas flows from the supply through the valve and through the ice chamber in the product chamber.
  • the gas takes in the ice chamber with arranged ice crystals. This can be done for example by taking an ice mist. It is also possible that ice crystals or deposits of ice crystals are separated and / or broken up in the ice chamber by the flowing gas, which then the entrainment of ice crystals can be carried by the gas to the product chamber.
  • the present invention is based on the finding that in the use of ice crystals in the form of an ice mist or of deposited ice crystals in an ice chamber according to the patents US 8,839,528 B2 and US 8,875,413 B2 necessarily a pressure difference between the product chamber and the ice chamber must be brought about. This necessarily requires the arrangement of a valve between the ice chamber and the product chamber, which u. U. the equipment cost is increased. Furthermore, a control of this valve to generate the pressure difference on the one hand and to generate the pressure compensation for the supply of ice crystals to the product chamber on the other hand required, so special control measures are taken. Such a valve is dispensable for the inventive design or in the event that such a valve is available for other purposes, a control of the valve during the production of ice crystals and the implementation of the "Controlled Nucleation" is not required.
  • freeze-dryer comprising the product chamber on the one hand and an assembly forming the ice chamber are separately formed as singular components, which can then be connected to one another via fluidic and / or electrical lines.
  • a particularly compact embodiment of the freeze-drying plant according to the invention results when the ice chamber is structurally integrated into the freeze dryer.
  • the ice chamber in the freeze dryer is formed separately from an ice condenser chamber of the freeze dryer which serves to condense sublimed solvent produced during primary drying.
  • the design of the ice chamber and the control of the process conditions (such as pressure and temperature) in this regardless of the design of the ice condenser chamber and the process conditions in this can be done, resulting in an extended design margin.
  • the ice chamber is formed by the ice condenser chamber of the freeze dryer itself, so that there is a multifunctional ice condenser chamber:
  • This multifunctional Eiskondensatorhunt is thus initially used as an ice chamber for generating and / or storing the ice crystals, which are then used for the "Controlled Nucleation", and then at a later time for the resublimation of the solvent sublimated during the primary drying.
  • the ice chamber is formed separately from the freeze dryer.
  • the ice chamber is connected via a line to a connection of the freeze dryer.
  • This connection opens into the product chamber or ice condenser chamber.
  • the line and thus the connection between the ice chamber and the connection of the freeze dryer and the product chamber is permanently open (or this line is open at least for the time of generation of the ice crystals and the supply of ice crystals to the product chamber during the "Controlled Nucleation", if a switchable closure element is arranged here.)
  • a flow guide element is present in the ice chamber or ice condenser chamber. This flow guide element directs the flowing gas of the supply in the direction of deposition surfaces for the ice crystals in the ice chamber. Alternatively or additionally, a deflection of the gas can take place via the flow guide element.
  • the flow guide element is designed as a kind of lance, by means of which the flowing gas is supplied to a favorable location in the ice chamber or ice condenser chamber, from where then the gas is guided past the deposition surfaces and a particularly good entrainment of ice crystals can take place.
  • the use of a diffuser or a throttle for the flow guide element whereby influence on the flow velocity and the pressure of the flowing gas can be taken such that optimal entrainment of the ice crystals can be done by the gas.
  • the flow guide element is formed with a kind of "distribution head" with branches and multiple outlet openings, from where the gas can escape in the direction of different locations of the deposition surfaces for the ice crystals, so that the gas can take or tear ice crystals from different locations ,
  • the supply is formed with a reservoir in which directly the pressurized gas or the liquid (in particular liquid nitrogen) from which the pressurized gas is generated is arranged.
  • the storage container has a cooling and / or heating device, via which a cooling or heating of the fluid arranged in the reservoir is possible.
  • the flowing gas may have a cooled temperature with regard to the entrainment of the ice crystals, the maintenance of the ice crystals in the supply to the product chamber and / or the generation of nuclei for ice crystal formation and ice crystal growth in which the material to be dried is optimized.
  • boiling of a liquid (in particular liquid nitrogen) arranged in the reservoir is deliberately prevented by cooling or deliberately brought about and controlled by heating.
  • any gas can be used as the gas, as long as it meets the requirements for the purity of the lyophilizate.
  • the use of liquid nitrogen as a fluid in the supply has proven to be particularly advantageous, which on the one hand meets the requirements for product purity, can be provided in a cost-effective manner (for large and / or regular quantities), is suitable for providing a gas under pressure, and may also be used for cooling.
  • a freeze drier (as a singular unit) may have an ice condenser chamber and a product chamber, the integral configuration of the ice condenser chamber with the product chamber being the same, as is the case for so-called single-chamber freeze dryers.
  • the freeze dryer has a connection for a supply or for an ice chamber.
  • the freeze dryer has a control output.
  • the control output is intended for a control signal for a valve which is arranged between a supply (by means of which a pressurized gas is provided, the pressure of the supplied gas being greater than the pressure in the product chamber) and the ice chamber.
  • the freeze dryer has a control unit with control logic.
  • the control unit generates, with the control logic, the control signal supplied to the control output, which opens the valve.
  • This control signal is generated at a time when ice crystals are present or produced in the ice chamber and to which the ice chamber is connected via an opening to the product chamber (which is a permanently open or open only during this process Condition may be the case). With such opening of the valve gas can flow from the supply through the valve, through the ice chamber with the entrainment of ice crystals in the product chamber. Also possible is an embodiment in which a freeze dryer with an ice condenser chamber and a product chamber per se is not equipped with the possibilities of "controlled nucleation".
  • such a conventional freeze dryer can be additionally equipped with a control logic on an existing or supplemented control unit, which as explained above, generates a control signal, which is then supplied to the control output.
  • the "Controlled Nucleation" for a conventional freeze drier thus only by supplementing the control logic, so update of the control software, and connection of supply and / or ice chamber and valve to the said connection of the freeze dryer and its control output can be retrofitted so that the " Controlled Nucleation "is enabled.
  • a technical vacuum for example less than 100 mbar, less than 70 mbar, less than 50 mbar, less than 30 mbar or even less than 15 mbar
  • a technical vacuum for example less than 100 mbar, less than 70 mbar, less than 50 mbar, less than 30 mbar or even less than 15 mbar
  • a technical vacuum for example less than 100 mbar, less than 70 mbar, less than 50 mbar, less than 30 mbar or even less than 15 mbar
  • ice crystals are then produced from evaporated solvent of the material to be dried, wherein only ice crystals from the evaporated solvent of the material to be dried or other ice crystals can be produced.
  • the valve which is arranged between the supply and the ice chamber, opened. With the opening of this valve gas flows from the supply through the valve and through the ice chamber with the entrainment of ice crystals in the product chamber.
  • the fluid in the reservoir is cooled. Furthermore, the gas can be guided and / or deflected via a flow-guiding element in the region of the ice crystals.
  • the generation of the ice crystals in the ice chamber can take place with deposition of ice crystals on deposition surfaces of the ice chamber and / or by generating an ice mist in the ice chamber.
  • Fig. 1 shows a freeze dryer 1 with a freeze dryer 2.
  • the freeze dryer 2 has a product chamber 3.
  • a plurality of shelves 4a, 4b, 4c, ... are arranged one above the other.
  • On the shelves 4 each have a plurality of vials 5 each arranged therein Trocknungsgut 6 (wherein for simplicity in Fig. 1 only the vials 5 are shown on a footprint 4c).
  • an ice condenser chamber 7 is integrated in the freeze dryer 2.
  • the product chamber 3 and the ice condenser chamber 7 are arranged in a common housing 8 of the freeze dryer 2.
  • a cooling device 9 here a cooling coil 10 is arranged.
  • the ice condenser chamber 7 is used as the ice chamber 11.
  • the cooling device 9 or the cooling coil 10 forms deposition surfaces 20 for ice crystals.
  • the product chamber 3 on the one hand and the ice condenser chamber 7 / ice chamber 11 are for the in Fig. 1 illustrated embodiment partially separated by an intermediate wall 12.
  • This intermediate wall has (at least) an opening 13 through which the product chamber 3 with the ice condenser chamber 7 / ice chamber 11 is connected (and vice versa).
  • the intermediate wall 12 is completely eliminated, so that the product chamber 3 is formed integrally with the ice condenser chamber 7 / ice chamber 11, without thereby leaving the scope of the invention.
  • a closure device 14 is shown, which is in its open position and which at least partially closes the opening 13 in the closed state.
  • the closure device 14 is located both during the production of ice crystals in the ice chamber 11 and during the loading of the vials 5 in the product chamber 3 with the ice crystals in the open position.
  • the freeze drier 2 has a connection 15 for a supply 16, which is formed here with a storage container 44 filled with the gas and under pressure.
  • the flow guide element 11 has at least one outlet opening 19 which is preferably arranged adjacent to the deposition surfaces 20 in such a way that the Outlet opening 19 escaping gas along the deposition surfaces 20 is guided.
  • the connection 15 of the freeze dryer 2 is connected to the supply 16 via a fluidic line 21 with a branch 22 and a valve 23.
  • In the stock 16 may optionally be arranged a cooling and / or heating device 24.
  • a port 25 of the reservoir 16 is connected via a valve 26 to a fluid or gas source, in particular for liquid nitrogen.
  • a further fluidic line 27, in which a further valve 28 is arranged branches off to a suction port 29 of a pump 30.
  • the supply 16 may be part of a retrofit unit or a retrofit kit in which it forms a nucleator additional container 45, with which a conventional freeze drier 2 can be retrofitted to enable a "Controlled Nucleation".
  • an electronic control unit 31 The control of the above-explained method steps is carried out by an electronic control unit 31.
  • the electronic control unit 31 is arranged externally of the freeze dryer 2. It is also quite possible that the electronic control unit 31 is attached to the freeze dryer 2 or is integrated in it.
  • the freeze dryer 2 is basically the same Fig. 1 and the associated description.
  • the ice condenser chamber 7 is not additionally used as an ice chamber 11.
  • the freeze drier 2 has a connection 38, which here opens into the product chamber 3, but can also open into the ice condenser chamber 7 in a divergent manner.
  • the connection 38 is connected via a fluidic line 39 to the ice chamber 11 arranged externally here.
  • the continuous line cross-section of the line 39 and the terminal 38 in this case forms an opening 40, which permanently connects the ice chamber 11 with the product chamber 3 at least during the relevant process steps with the production of ice crystals and the loading of the vials 5 with the ice crystals.
  • the ice chamber 11 has a venting port 41, which is connected via a valve 42 to the suction port 29 of the pump 30. Furthermore, a connection 43 of the ice chamber 11 via a valve 23 with a supply 16, not shown here, in particular a source of liquid nitrogen, connected.
  • the external ice chamber 11 may be part of a retrofit unit or a retrofit kit in which it forms a nucleator additional container 45 and with which a conventional freeze dryer 2 can be retrofitted to enable a "controlled nucleation".
  • control unit 31 controls the pump 30, while the control lines 33, 35 of the control of the valve 42 and 23 are used.
  • the volume of the reservoir 44 is about seven liters, while the volume of the product chamber 3 and the ice chamber 11 together is 125 liters.
  • temperatures in the range of -100 ° C to -50 ° C are preferably achieved.
  • the starting point here is a conventional freeze-drying plant, which does not allow "controlled nucleation" of the material to be dried by subjecting the products in a drying chamber to a flowing, ice-crystal-containing gas.
  • a retrofit kit comprising a nucleator supplemental vessel, which is an ice chamber or supply to convert the aforesaid conventional freeze dryer to a freeze dryer as previously discussed, and which provides controlled nucleation of the product to be dried by subjecting the products to a drying chamber, is then used with a flowing, ice crystals containing gas allows.
  • a nucleator supplemental vessel which is an ice chamber or supply to convert the aforesaid conventional freeze dryer to a freeze dryer as previously discussed, and which provides controlled nucleation of the product to be dried by subjecting the products to a drying chamber, is then used with a flowing, ice crystals containing gas allows.
  • the retrofit kit may include a software update, in particular a data carrier with control logic for a software update.
  • the software update modifies the control logic of a control unit already present in the conventional freeze dryer. The modification is made such that at a time when ice crystals are present or produced in an ice chamber, which may be formed by the condenser chamber or formed as a separate ice chamber, and to which the ice chamber is connected to the product chamber via an orifice is, a control signal is generated. This control signal opens a valve.
  • valve With the opening of the valve flows gas, which from the supply, which may be formed as a separate supply or may be formed integrally with the ice chamber is provided, flows through the valve and through the ice chamber with entrainment of ice crystals in the product chamber, whereby the " Controlled Nucleation "takes place.
  • the control unit of the conventional freeze dryer By means of the software update using the control unit of the conventional freeze dryer, the control of the "Controlled Nucleation" done.
  • the retrofit kit may have a valve. This valve is placed between the or a supply and one of the ice chamber. By controlling the valve via the control logic, possibly modified by the software update, the Controlled Nucleation can be controlled.
  • a retrofit kit or a retrofit unit in particular an ice chamber and / or a supply, is connected to a plurality of freeze dryers, so that this or this, for example, alternately or depending on which freeze dryer is currently being used, for the "Controlled Nucleation "can be used in the several freeze dryers.

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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)

Claims (13)

  1. Installation de lyophilisation (1), avec
    a) une chambre de produits (3), dans laquelle des produits traversent un processus de lyophilisation, et
    b) une chambre à glace (11) destinée à la production de cristaux de glace,
    c) une vanne (23), qui est disposée entre
    ca) une réserve (16) qui peut fournir un gaz sous une pression qui est supérieure à la pression dans la chambre de produits (3), et
    cb) la chambre à glace (11),
    d) la réserve (16), la vanne (23), la chambre à glace (11) et la chambre de produits (3) étant montées les unes derrière les autres dans cet ordre,
    e) et avec une unité de commande (31),
    caractérisée en ce que
    f) l'unité de commande (31) possède une logique de commande qui, à un moment où
    fa) il y a des cristaux de glace dans la chambre à glace (11) et
    fb) la chambre à glace (11) est raccordée à la chambre de produits (3) par le biais d'un orifice (13),
    produit un signal de commande qui ouvre la vanne (23), ce qui fait que du gaz s'écoule dans la chambre de produits (3) à partir de la réserve (16) à travers la vanne (23) et à travers la chambre à glace (11) en emportant des cristaux de glace.
  2. Installation de lyophilisation (1) selon la revendication 1, caractérisée en ce que la chambre à glace (11) est intégrée, au plan de la construction, dans un lyophilisateur (2) .
  3. Installation de lyophilisation (1) selon la revendication 2, caractérisée en ce que la chambre à glace (11) est constituée d'une chambre de condenseur à glace (7) du lyophilisateur (2).
  4. Installation de lyophilisation (1) selon la revendication 1, caractérisée en ce que
    a) la chambre à glace (11) est constituée séparément du lyophilisateur (2), et
    b) la chambre à glace (11) est raccordée au lyophilisateur (2) par le biais d'une conduite (39) avec un raccordement (38) du lyophilisateur (2) qui débouche dans la chambre de produits (3) ou la chambre du condenseur à glace (7).
  5. Installation de lyophilisation (1) selon l'une des revendications précédentes, caractérisée en ce que, dans la chambre à glace (11) ou la chambre de condenseur à glace (7), il y a un élément de guidage d'écoulement (17) qui, en direction de surfaces de dépôt (20) pour des cristaux de glace, dirige et/ou dévie du gaz qui est fourni par la réserve (16) .
  6. Installation de lyophilisation (1) selon l'une des revendications précédentes, caractérisée en ce que la réserve (16) est formée avec un réservoir de stockage (44).
  7. Installation de lyophilisation (1) selon la revendication 6, caractérisée en ce que le réservoir de stockage (44) dispose d'un dispositif de chauffage et/ou de refroidissement (24) destiné au chauffage et/ou au refroidissement du fluide sous pression dans le réservoir de stockage (44).
  8. Installation de lyophilisation (1) selon l'une des revendications précédentes, caractérisée en ce que la réserve (16) est formée avec de l'azote liquide.
  9. Procédé de commande d'une installation de lyophilisation (1) selon l'une des revendications 1 à 8, dans lequel
    a) dans la chambre de produits (3) et dans la chambre à glace (11) qui lui est raccordée par le biais de l'orifice (13), un vide technique et une température inférieure à la température de congélation de l'article à sécher (6) sont établis conjointement,
    caractérisé en ce que
    b) des cristaux de glace sont produits dans la chambre à glace (11) à partir de solvant évaporé de l'article à sécher (6), et
    c) une vanne (23) qui est disposée entre une réserve (16) qui fournit un gaz sous pression - la pression du gaz fourni étant supérieure à la pression dans la chambre de produits (3) et dans la chambre à glace (11) - et la chambre à glace (11) est ouverte, ce qui fait que du gaz s'écoule dans la chambre de produits (3) à partir de la réserve (16) à travers la vanne (23) et à travers la chambre à glace (11) en emportant des cristaux de glace.
  10. Procédé selon la revendication 9, caractérisé en ce que le fluide est refroidi et/ou chauffé dans la réserve (16) par le biais d'un dispositif de chauffage et/ou de refroidissement (24) .
  11. Procédé selon l'une des revendications 9 et 10, caractérisé en ce que le gaz est guidé et/ou dévié par le biais d'un élément de guidage d'écoulement (17) situé dans la zone des cristaux de glace.
  12. Procédé selon l'une des revendications 9 à 11, caractérisé en ce que des cristaux de glace sont déposés sur des surfaces de dépôt (20) dans la chambre à glace (11).
  13. Procédé selon l'une des revendications 9 à 12, caractérisé en ce qu'un nuage de glace avec des cristaux de glace est produit dans la chambre à glace (11).
EP15167172.4A 2015-05-11 2015-05-11 Installation de lyophilisation Active EP3093597B1 (fr)

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PCT/EP2016/055439 WO2016180558A1 (fr) 2015-05-11 2016-03-14 Installation de lyophilisation

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Publication number Priority date Publication date Assignee Title
SI3392584T1 (sl) 2017-04-21 2020-09-30 Gea Lyophil Gmbh Zamrzovalni sušilnik in postopek za induciranje nukleacije v proizvodih
CN107166947A (zh) * 2017-05-23 2017-09-15 上海工程技术大学 一种基于薄膜电阻的冻干机节能除霜装置
ES2779023T3 (es) 2017-10-20 2020-08-13 Martin Christ Gefriertrocknungsanlagen Gmbh Procedimiento para la determinación a base de presión de un parámetro de producto en un liofilizador, liofilizador y producto de software
WO2019192747A1 (fr) * 2018-04-05 2019-10-10 Paechnatz Torsten Installation de lyophilisation et procédé associé
CN108371210B (zh) * 2018-04-19 2023-08-29 天津商业大学 一种真空预冷与制取冰晶组合系统
DE202021101537U1 (de) * 2021-03-24 2021-05-18 Torsten Pächnatz Gefriertrocknungsanlage
CN113357879B (zh) * 2021-04-30 2023-10-10 杭州富睿捷科技有限公司 一种冻干设备

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2994132A (en) * 1956-08-22 1961-08-01 Neumann Karlheinz Freeze drying apparatus
US8240065B2 (en) 2007-02-05 2012-08-14 Praxair Technology, Inc. Freeze-dryer and method of controlling the same
US20110179667A1 (en) 2009-09-17 2011-07-28 Lee Ron C Freeze drying system
US8839528B2 (en) 2011-04-29 2014-09-23 Millrock Technology, Inc. Controlled nucleation during freezing step of freeze drying cycle using pressure differential ice fog distribution
US8875413B2 (en) 2012-08-13 2014-11-04 Millrock Technology, Inc. Controlled nucleation during freezing step of freeze drying cycle using pressure differential ice crystals distribution from condensed frost

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

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