EP3443286B1 - Dispositif de sublimation et procédé de lyophilisation - Google Patents

Dispositif de sublimation et procédé de lyophilisation Download PDF

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Publication number
EP3443286B1
EP3443286B1 EP17719667.2A EP17719667A EP3443286B1 EP 3443286 B1 EP3443286 B1 EP 3443286B1 EP 17719667 A EP17719667 A EP 17719667A EP 3443286 B1 EP3443286 B1 EP 3443286B1
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EP
European Patent Office
Prior art keywords
evaporation chamber
chamber
products
rotation
freeze
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EP17719667.2A
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German (de)
English (en)
French (fr)
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EP3443286A1 (fr
Inventor
Jean Delaveau
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Individual
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Individual
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Priority claimed from FR1653298A external-priority patent/FR3050262B1/fr
Priority claimed from FR1653297A external-priority patent/FR3050261B1/fr
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Publication of EP3443286A1 publication Critical patent/EP3443286A1/fr
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    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F26—DRYING
    • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
    • F26B11/00—Machines or apparatus for drying solid materials or objects with movement which is non-progressive
    • F26B11/02—Machines or apparatus for drying solid materials or objects with movement which is non-progressive in moving drums or other mainly-closed receptacles
    • F26B11/04—Machines or apparatus for drying solid materials or objects with movement which is non-progressive in moving drums or other mainly-closed receptacles rotating about a horizontal or slightly-inclined axis
    • F26B11/049—Machines or apparatus for drying solid materials or objects with movement which is non-progressive in moving drums or other mainly-closed receptacles rotating about a horizontal or slightly-inclined axis with provisions for working under increased or reduced pressure, with or without heating
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F26—DRYING
    • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
    • F26B11/00—Machines or apparatus for drying solid materials or objects with movement which is non-progressive
    • F26B11/02—Machines or apparatus for drying solid materials or objects with movement which is non-progressive in moving drums or other mainly-closed receptacles
    • F26B11/026—Arrangements for charging or discharging the materials to be dried, e.g. discharging by reversing drum rotation, using spiral-type inserts
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F26—DRYING
    • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
    • F26B11/00—Machines or apparatus for drying solid materials or objects with movement which is non-progressive
    • F26B11/02—Machines or apparatus for drying solid materials or objects with movement which is non-progressive in moving drums or other mainly-closed receptacles
    • F26B11/04—Machines or apparatus for drying solid materials or objects with movement which is non-progressive in moving drums or other mainly-closed receptacles rotating about a horizontal or slightly-inclined axis
    • F26B11/0445—Machines or apparatus for drying solid materials or objects with movement which is non-progressive in moving drums or other mainly-closed receptacles rotating about a horizontal or slightly-inclined axis having conductive heating arrangements, e.g. heated drum wall

Definitions

  • the invention relates to the field of devices providing treatment of products by lyophilization.
  • the invention relates more particularly to devices carrying out bulk sublimation.
  • the invention also relates to a bulk lyophilization process.
  • the invention finds a particularly advantageous application in the fields of pharmaceutical preparation and food preparation and, more generally, for all industries with high added value which require a method of preservation by lyophilization.
  • the invention can be implemented in the field of biotechnology for the production of inoculum for the fermentation of biomass, in the food field for the freeze-drying of fruits, vegetables, beverages and food preparations, in the health sector for the freeze-drying of proteins, peptides, enzymes, bacteria, viruses, living cells, sensitive formulation based on antibodies or sensitive molecules, plasma fraction or formulation of sensitive polymers .
  • Lyophilization is a low temperature dehydration operation which consists in removing by sublimation most of the water contained in a product. Lyophilization allows high quality end products to be obtained without degrading the structure and retaining a large part of the activity of microorganisms or cells. Freeze-dried products exhibit long-term storage capacity due to lowering of the water activity of the product.
  • lyophilization is, on the other hand, limited by its cost and remains much lower than the use of drying.
  • the low productivity in lyophilization is due to the discontinuous mode of operation under vacuum and at very low temperature which results in long treatment times of between ten hours and several days. In these extreme conditions, the heat transfers have a very low efficiency.
  • the drying is conventionally carried out at atmospheric pressure with very low temperatures, generally between 50 and 100 ° C, and a heat transfer with better efficiency.
  • the investment and operating costs of freeze-drying devices are high.
  • the energy consumption of a freeze-drying device is typically of the order of 2500 to 6000 kWh per ton of water to be eliminated.
  • freeze-drying is only applicable for products with high added value.
  • drying processes based on atomization or fluidized bed are commonly used because they are significantly cheaper.
  • the sectors of pharmaceutical industries vacuums, serum, drugs
  • bio-industries semi-industries
  • freeze-drying process which alone allows them to obtain the most characteristic property of the technique, namely preservation. of an active principle (biological and / or medicinal activity) in a product which will be stored at a temperature close to room temperature.
  • Lyophilization requires the use of a device which consists of a freezing chamber connected to cooling means, an evaporation chamber connected to heating means and a condensation chamber connected to the chamber. evaporation.
  • the condensation chamber is configured to collect water vapor from the evaporation chamber on an ice trap.
  • the evaporation chamber also freezes the products prior to evaporation.
  • freezing is conventionally carried out in an independent device, so that the actual freeze-drying device only comprises an evaporation chamber and a condensation chamber.
  • Cooling means are arranged in the condensation chamber to freeze the water vapor coming from the evaporation chamber.
  • the water in the form of vapor then turns to ice in the condensation chamber and the ice is stored in the condensation chamber on the ice trap.
  • freezing and sublimation can be carried out within the same enclosure.
  • the freezing chamber and the evaporation chamber consist of one and the same chamber connected to the cooling means and to the heating means.
  • the chambers are also placed under vacuum by a vacuum pump so as to pass under the triple point of water and allow the passage of water from the solid phase to the gas phase.
  • the lyophilization process has a first step consisting in freezing the products in the freezing and evaporation chamber to allow them to be dried at low temperature. Rapid freezing is sought so as to form small ice crystals. Too slow freezing has the effect of promoting the formation of large crystals capable of damaging the structure of the product by tearing the walls of its cells, for example for yeasts, viruses and animal or plant cells.
  • a second step is to create a vacuum in the evaporation chamber, the low pressure, generally well below 6.1 hPa, allowing water in the form of ice to turn into vapor without thawing the products.
  • the products receive a heat input to provide the energy necessary for the latent heat of the sublimation of the ice into vapor.
  • the vapor enters the condensing chamber while the condensing chamber is conditioned to transform water vapor into ice by the use of an ice trap maintained at a very low temperature, generally -60 ° C.
  • freeze-drying process thus makes it possible to extract up to 95% of the water contained in the products. Freeze drying can reduce product moisture to an extremely low rate, between 1% and 10% of the product density, and prevent bacteria and mold from growing and enzymes from triggering chemical reactions that can damage the product. It follows that freeze-dried products can be stored for a very long time. In airtight packaging, protected from moisture, light and oxygen, freeze-dried products can be stored at room temperature for many years. In addition, the high quality of sterilized products also requires sterilization of the sterilization chain.
  • freeze-drying time depends on the particle size of the products to be freeze-dried and the surface of the products coming into contact with the heat source.
  • a conventional solution consists in distributing the products to be freeze-dried in small bottles.
  • the heat source is configured to heat the base of the vials so as to transmit heat to all of the products stored in the vials by conduction and radiation. After freeze-drying, the product appears in the form of a porous cake taking the shape of the bottle.
  • the average freeze-drying time is thus between two and three days due to the time of heat migration by conduction and by radiation in the flasks.
  • the distribution of the products to be lyophilized in a large number of flasks requires a large size of the evaporation chamber. It follows that the power of the heating means, of the cooling means and of the vacuum means must be increased accordingly.
  • Bulk lyophilization makes it possible to obtain an average lyophilization time of between five and fifty hours.
  • the reduction in freeze-drying time makes it possible to reduce consumption, production time and therefore production cost.
  • limiting the freeze-drying time reduces the exposure of the product to heat. It is thus possible to improve the quality of the lyophilized product.
  • EP 2,578,975 and EP 2,578,976 also propose to reduce the freeze-drying time by implementing bulk freeze-drying.
  • the evaporation chamber is mounted on an axis driven in rotation during lyophilization.
  • the evaporation chamber is mounted in a sterile enclosure and the axis of the chamber emerges from the enclosure through an opening in order to be driven by a motor.
  • a seal is positioned around the axis at the opening of the enclosure to ensure that the enclosure is evacuated without loss of pressure at the opening. This seal is configured to withstand pressures of 2.5 bars for temperatures varying between -60 and 120 ° C.
  • an operator connects a sterile inlet to the evaporation chamber passing through the sterile enclosure so as to reach the tank.
  • the products to be lyophilized are then placed in the tank, passing through the sterile inlet and the sterile enclosure.
  • the operator then disconnects the input while taking care to maintain sterility in the enclosure.
  • Lyophilization is then carried out while the motor drives the tank in rotation so as to stir the products to prevent their agglomeration.
  • the evaporation and condensation chambers are in communication but do not rotate.
  • the operator connects a sterile outlet to the evaporation chamber via the sterile enclosure so as to extract the lyophilized products from the tank.
  • freeze-drying devices require operator handling steps between two freeze-dryings. It follows that freeze-drying is a treatment which is very little automated, thus increasing the production time and therefore the cost of the freeze-dried products.
  • the problem of the invention therefore consists in developing a device for freeze-drying bulk products that meets the drawbacks of the devices of the prior art.
  • the present invention aims to solve this problem by mounting the inlet and outlet of the evaporation chamber on flexible connectors and by agitating the evaporation and condensation chambers in a back and forth motion. It follows that the inlet and the outlet are permanently connected to the evaporation chamber and it is no longer necessary to mount the two chambers in a sterile enclosure.
  • the back and forth movement makes it possible to use heat transfer fluids circulating in double envelopes around the evaporation and condensation chambers by connecting the inlets and outlets of these fluids by flexible connectors.
  • heating and cooling can be carried out by conduction at the level of the bearing surface of the products in the evaporation chamber and by radiation on the rest of the surface of the evaporation chamber.
  • heat transfers can only be achieved by radiation around the evaporation and condensation chambers.
  • the heat transfers by conduction enabled by the invention improve the precision of the heat transfers and reduce consumption.
  • the inlet and outlet of products are immovably connected with the evaporation chamber.
  • the elimination of the enclosure limits the size of the device and the necessary power of the heating, cooling and evacuation means. It follows that the energy consumption of the freeze-drying device is reduced by 20 to 40% compared to the devices of the prior art for the same quantity of products.
  • This device makes it possible to carry out discontinuous lyophilization.
  • an operator supervises these manufacturing steps by means of temperature sensors arranged in the evaporation chamber and in the condensation chamber.
  • the freeze-drying can be carried out continuously by compartments provided in the evaporation chamber.
  • a third movement of rotation of the large amplitude axis allows the products to be lyophilized to be transferred between the compartments of the evaporation chamber so as to create a lyophilization path inside the evaporation chamber.
  • the invention makes it possible to carry out continuous lyophilization, that is to say that products can be introduced regularly over time without requiring the complete stopping of the lyophilization process.
  • products can be introduced by entering the first compartment of the evaporation chamber while other products placed in the evaporation chamber and in other compartments are still being lyophilized.
  • lyophilized products can be extracted from the evaporation chamber while other products are still being lyophilized.
  • the inlet comprises a loading chamber partitioned by two locks and the outlet comprises an unloading chamber partitioned by two locks.
  • the device is configured such that the opening of the lock separating the inlet of the evaporation chamber and the opening of the lock separating the outlet of the evaporation chamber are synchronized with the third movement of said motor.
  • This embodiment makes it possible not to interrupt the lyophilization cycle in order to introduce or extract products into the evaporation chamber.
  • the device comprises two condensation chambers connected to the evaporation chamber by two separate locks, the first condensation chamber being connected with the evaporation chamber by opening the first lock and closing the second lock so in using the first condensation chamber to trap the vapor coming from the evaporation chamber, the second condensation chamber then being regenerated when using the first condensation chamber and vice versa.
  • This embodiment makes it possible to empty the ice trapped in either of the condensation chambers without interrupting the continuous lyophilization process.
  • the device comprises two vacuum pumps, a first vacuum pump connected to the first condensation chamber and a second vacuum pump connected to the second condensation chamber.
  • This embodiment makes it possible to guarantee the evacuation of the condensation chambers when they are connected to the evaporation chamber and the depression of these chambers when they are in a regeneration phase.
  • the evaporation chamber is inclined between the inlet and the outlet. This embodiment makes it possible to direct the products placed in one compartment towards the next compartment in the direction of the exit.
  • the axis can be inclined only during the movement of great amplitude intended for the transfer of the product between two compartments.
  • the partitions of the evaporation chamber have two distinct shapes mounted alternately in the evaporation chamber, the two shapes having notches axially offset and intended for the passage of the product to be freeze-dried between two compartments.
  • the axial offset of two consecutive partitions makes it possible to limit the risk of the product moving between several compartments during the large amplitude movement aimed at transferring the product between two compartments.
  • the motor is configured to drive the axis according to a fourth movement complementary to the three movements, the fourth movement causing the axis to rotate on itself in a direction opposite to the direction of the third movement with an angle of rotation between 90 ° and 180 ° so as to move the products between two consecutive compartments of the evaporation chamber.
  • This embodiment also makes it possible to improve the transfer of the product between two consecutive compartments.
  • an operator supervises these manufacturing steps by means of temperature sensors arranged in the evaporation chamber and in the condensation chamber.
  • the device used is suitable for continuous or discontinuous lyophilization, it may also have the following characteristics.
  • the evaporation chamber is disposed laterally with respect to the condensation chamber or chambers.
  • a vapor sensor can be placed between the evaporation chamber and the condensation chamber, for example by means of a propeller driven by the flow of vapor between the evaporation chamber and the condensation chamber during the sublimation.
  • the evaporation and condensation chambers are in the form of a tank of generally cylindrical shape.
  • the evaporation chamber has a capacity of between 0.01 and 1 m 3 up to 10 m 3 .
  • products already frozen are introduced into the evaporation chamber.
  • the product entry is configured to introduce frozen products.
  • This embodiment makes it possible to separate the freezing step from the evaporation step.
  • the freezing is thus carried out independently and the frozen products are preferably in the form of pellets, granules or frozen particles.
  • the device also comprises means for cooling the evaporation chamber.
  • This embodiment makes it possible to use the evaporation chamber to carry out the freezing of the products with the sublimation step.
  • the products can be introduced into the evaporation chamber at ambient temperature and a first step consists in freezing the products directly in the evaporation chamber before carrying out the sublimation.
  • the back and forth movement of the evaporation chamber can be implemented during freezing.
  • said chamber comprises an external double wall, the heating means being configured to circulate a heat transfer fluid in a space formed between the two walls of the evaporation chamber.
  • This embodiment limits the size of the device and the consumption of the heating means.
  • the means for cooling the condensation chamber and the means for heating the evaporation chamber are connected to their respective chambers by flexible connectors.
  • This embodiment makes it possible to deport the energy production devices outside the mobile structure formed by the two chambers. Therefore, heating and cooling can be achieved both by conduction at the wall of the chamber with which the surface of the products is in contact and by radiation. This improves the precision of heat transfers and reduces consumption.
  • the flexible connectors have several stainless steel turns. This embodiment makes it possible to avoid strain hardening of the metal forming the flexible connectors.
  • the connectors can be made of a plastic material or of a material treated to avoid strain hardening.
  • the evaporation chamber comprises baffles arranged inside the evaporation chamber so as to promote mixing of the products during movements of the evaporation chamber.
  • the baffles thus ensure mixing of the products during freeze-drying.
  • the device also comprises a first temperature sensor and a pressure sensor arranged in the evaporation chamber and a second temperature sensor arranged in the condensation chamber. This embodiment makes it possible to monitor the temperatures and the pressure in order to estimate the progress of the lyophilization process.
  • the figure 1 illustrates a freeze-drying device comprising an evaporation chamber 5 and a condensation chamber 10.
  • An inlet 1 in the form of a hopper is connected to the evaporation chamber 5 via a flexible connector.
  • the hopper is also equipped with a first lock 2 so as to introduce products to be freeze-dried when the lock 2 is open.
  • An outlet 8 in the form of a hopper is also connected to the evaporation chamber 5 via a flexible connector.
  • the hopper is also equipped with a second lock 9 so as to extract the lyophilized products when the lock 9 is open.
  • Locks 2 and 9 also make it possible to guarantee the tightness and sterility of chambers 5, 10.
  • locks 2, 9 of the “Agilent Technologies” or “Gericke” brand can be used.
  • the invention can be implemented with a single input / output performing the two functions of introducing and extracting the products.
  • the evaporation chamber 5 and the condensation chamber 10 are arranged in the extension of one another and independent of each other, that is to say that the two chambers form two spaces offset axially. .
  • the condensation chamber 10 can be arranged around the evaporation chamber 5 , the two chambers are in this case concentric.
  • the evaporation chamber 5 has an external double wall in which a heat transfer liquid circulates to heat the evaporation chamber 5.
  • the internal surface of the evaporation chamber 5 is mirror polished so as to promote the sliding of the evaporation chamber. load and minimize the slope angle.
  • the heat transfer liquid is heated by an external device connected to the double wall by a fluid inlet 15 and a fluid outlet 16 .
  • a steam inlet 31 is also connected to the evaporation chamber 5 in order to sterilize the evaporation chamber 5 .
  • heating means 15 , 16 make it possible to sublimate the frozen products placed in the evaporation chamber.
  • the heat transfer fluid can be heated by a heat exchanger coupled to an external heat source.
  • Products can be introduced in frozen form through inlet 1 .
  • the products can be frozen directly in the evaporation chamber 5 .
  • the products are introduced at room temperature and the heat transfer fluid circulating in the outer double wall is refrigerated at a very low temperature, for example of the order of -60 ° C, so as to cause the freezing of the products. products before the evaporation step. Freezing can also be carried out in inlet 1. For example, freezing can be obtained directly in pellets by means of a drip falling into a stream of nitrogen.
  • the condensation chamber 10 is connected to the evaporation chamber 5 via an airlock 4.
  • the airlock 4 is configured to allow the vapor to pass between the evaporation chamber 5 and the condensation chamber 10 .
  • the airlock 4 may include a grid or a filter allowing the vapor to pass and retaining the particles of the product which risk being entrained by the water vapor.
  • the filter is made of Gore-Tex®, registered trademark.
  • the condensation chamber 10 comprises an ice trap 11 in the form of a coiled tube in which circulates a heat transfer fluid, for example liquid nitrogen.
  • the heat transfer fluid is produced by an external device and it is conducted in the pipe through an inlet 17 to an outlet 18 .
  • the heat transfer fluid can be cooled by a heat exchanger coupled to an external cold source.
  • the cooling means 17 , 18 are implemented when the airlock 4 is open and the steam enters the condensation chamber. The steam then freezes on the tube of the ice trap 11 . The number of turns and the section of the tube forming the ice trap 11 are determined as a function of the quantity of vapor to be recovered.
  • a steam inlet 32 is also connected to the condensation chamber 10 in order to sterilize the condensation and evaporation chambers 10 prior to the start of the lyophilization process itself. To do this, in a step prior to lyophilization, the airlock 4 is opened and steam is introduced into the two chambers 5 , 10 .
  • the steam injected by the steam injection nozzle 32 causes the ice present on the ice trap 11 to melt.
  • a purge 33 thus extracts the steam injected to evaporate the ice contained in the condensation chamber 10 as well as the steam generated for sterilization.
  • the condensation chamber 10 is also connected to a vacuum pump 6 via a pipe fitted with a valve 7 .
  • This vacuum pump 6 is configured to evacuate the condensation chamber 10 and the evaporation chamber 5 when the airlock 4 is open.
  • the valve 7 is kept open and the vacuum is maintained by the condensation of the vapor on the ice trap 11.
  • the inlet 1 and the outlet 8 of the inlet and outlet hoppers are connected to the evaporation chamber 5 by sterile flexible sleeves.
  • the heating and cooling means of the two chambers 5 , 10 as well as the vacuum pump 6 are also connected to the respective chambers by flexible connectors.
  • the flexible connectors are made of stainless steel to meet sterility constraints.
  • the flexible connectors advantageously have turns so as to limit the strain hardening of the stainless steel. Alternatively, other materials can be used without changing the invention.
  • the function of the flexible connectors is to connect a fixed and external element, in this case the feed and discharge hoppers to the chambers 5 , 10 so as to guarantee a connection of these elements with the chambers 5 , 10 when these chambers are rotated on themselves by the motor 12 .
  • the bending capacity of these connectors thus makes it possible to absorb the displacements of the chambers 5 , 10 relative to the external elements.
  • the length of the connectors is also chosen to ensure that the connection is maintained when the chambers 5 , 10 are rotated .
  • flexible connectors of the brand “Stäubli®” can be used.
  • the two chambers 5 , 10 are mounted integral on an axis 30.
  • the two chambers are cylindrical and the axis 30 passes through the center of the two plane faces of the cylinders so as to uniformly distribute the mass of the chambers 5 , 10 around of axis 30 .
  • the axis 30 is connected and made integral with the end of the condensation chamber 10 , opposite the end connected with the evaporation chamber 5 .
  • the axis 30 can be connected and made integral with the evaporation chamber 5 .
  • the axis 30 can be maintained, free to rotate, by supports.
  • the axis 30 is driven in rotation by a motor 12 .
  • two opposing rotational movements of the evaporation and condensation chambers with respect to their central axis are induced by the axis 30 driven by the motor 12 and are limited in amplitude so as to create a back and forth movement. is coming.
  • the figure 2 illustrates the positions of the axis 30 during this back and forth movement. In a first position, illustrated on the figure 2a , the axis 30 is not rotated by the motor 12 .
  • a first movement of the motor 12 illustrated on figure 2b , drives the axis 30 on itself and therefore the evaporation and condensation chambers in a first direction of rotation with an angular displacement ⁇ 1 less than 180 °.
  • a second movement of the motor 12 drives the axis 30 on itself and therefore the evaporation and condensation chambers in a second direction of rotation, opposite to the first direction of rotation, with an angular displacement a2 substantially equal to the angular displacement of the first movement.
  • the back and forth movement thus corresponds to a swing of the axis 30 , that is to say a rotation of the axis 30 on itself in one direction then in the other.
  • the axis 30 therefore does not perform a complete rotation thus limiting the risk of winding of the flexible connectors connecting the external devices to the chambers 5 , 10 .
  • flexible connectors are configured to deform and absorb the movements of the chambers 5 , 10 during the rotations so as to maintain a tight and sterile connection.
  • the evaporation chamber 5 also comprises baffles arranged inside the evaporation chamber 5.
  • the baffles extend radially towards the interior of the evaporation chamber 5 and make it possible to improve the mixing of the products during lyophilization.
  • coulters of the brand “Palamatic®” can be used.
  • the axis 30 can be mounted horizontally relative to the cylindrical body of the chambers 5 , 10.
  • the device advantageously comprises means for pivoting the axis in the vertical plane making it possible to guide the products placed in the chamber. evaporation 5 to outlet 8 when the lyophilization time is reached.
  • the axis 30 can be mounted with a bias, that is to say inclined in the vertical plane so as to guide the products towards the outlet 8 during the entire lyophilization process.
  • the outlet 8 is lower than the inlet 1 so as to use gravity to move the lyophilized products to the outlet 8 .
  • the chambers 5 , 10 are preferably instrumented by temperature 20 , 24 and pressure 21 sensors.
  • Two sensors 20 , 21 are arranged in the evaporation chamber 5 to control the temperature and the pressure in the evaporation chamber 5 .
  • a third sensor 24 is disposed in the condensation chamber 10 to control the temperature of the condensation chamber 10 . It follows that an operator can follow the freeze-drying process by means of the sensors 20 , 21 , 24 and estimate the quantity of water removed from the products over time. It is thus possible to determine the precise moment at which a desired water concentration is reached in order to stop lyophilization.
  • an operator opens lock 2 while lock 4, valve 7 and lock 9 are closed. Products to be lyophilized are thus introduced into the evaporation chamber 5, for example products previously frozen. Lock 2 is then closed and the airlock valve 4 is opened to connect the two chambers 5, 10.
  • the evacuation is then carried out by opening the valve 7 and actuating the vacuum pump 6.
  • the vacuum is essentially maintained by the condensation of the vapor on the trap 11 .
  • the next step is to sublimate the water contained in the frozen products.
  • the frozen products are heated by the actuation of the heating means 15 , 16 of the evaporation chamber 5 and the actuation of the cooling means 17 , 18 of the condensation chamber 10 .
  • the temperature of the products in the evaporation chamber 5 is moved from -30 ° C to -25 ° C under a vacuum of 6.1 hPa.
  • the water from the frozen products is then sublimated and enters the condensation chamber 10 in the form of vapor where it is frozen and trapped in the condensation chamber 10 by the ice trap 11 , the temperature of which is preferably between - 50 ° C and -60 ° C.
  • the grid or the membrane, preferably made of Gore-Tex®, present at the level of the airlock 4 can prevent the dissemination of product particles if the evaporation rate is high.
  • the motor 12 drives the axis 30 in rotation on itself according to the two movements described above. These movements are repeated alternately throughout the duration of the sublimation.
  • the motor can be a brushless electric motor (also called a “brushless” motor in the English literature).
  • the motor is an electric motor comprising several operating positions for which the magnetic field of the stator corresponds by an angular position of the rotor. Instead of moving the magnetic field of the stator in a circular fashion to drive the electric motor in a circular motion, the invention proposes to use the motor to perform a “back and forth” movement.
  • an electric motor which has four pairs of poles is conventionally driven in rotation by successively supplying the consecutive pairs of poles: the first pair of poles, the second pair of poles, the third pair of poles, the fourth pair of poles, the first pole pair ...
  • the "back and forth" motion can be generated by powering the first pole pair, then the second pole pair, then the first pole pair, then the fourth pole pair, then the first pole pair, then the second pole pair ...
  • the evaporation 5 and condensation 10 chambers can be mounted on wheels movable in the direction of rotation and configured to support the weight of the chambers.
  • the valve of the airlock 4 is closed and the heating 15 , 16 and cooling 17 , 18 means are stopped.
  • the lock 9 is open and the lyophilized products are extracted from the evaporation chamber 5 through the outlet 8 .
  • steam is introduced into the condensation chamber 10 through the steam injection nozzles 31 , 32 so as to cause a melting of ice and sterilization of the two chambers 5 , 10 .
  • the vapor thus contained in the two chambers 5 , 10 is extracted through the purge 33 or through the outlet 8 when the product is extracted from the condensation chamber 10 .
  • the lock 9 is closed, the two chambers 5 , 10 are cooled by means of the connectors 15-18 and a new lyophilization can be carried out.
  • the figure 3 illustrates a second embodiment in which the evaporation chamber 5 comprises partitions 40 extending over only a part of the height of the evaporation chamber 5 forming compartments between these partitions 40 .
  • the partitions 40 extend radially relative to the evaporation chamber 5 .
  • the top of each partition 40 is provided with a notch 39 intended to allow the passage of products between two consecutive compartments.
  • the figures 4 illustrate an exemplary embodiment of these partitions by the presence of a notch on the upper part of the partition 40 .
  • the device further comprises an inlet 1 connected to the evaporation chamber 5 via a loading chamber 41 so as to introduce products to be freeze-dried.
  • the loading chamber 41 is partitioned by two locks 2a , 2b .
  • Products are introduced into the loading chamber 41 from the inlet 1 when the first lock 2a is open.
  • the first sluice 2a is then closed and the second sluice 2b is open so as to introduce the products into the evaporation chamber 5 .
  • the outlet 8 is also connected to the evaporation chamber 5 via an unloading chamber 42 also partitioned between two sluices 9a , 9b .
  • the motor 12 induces at least three rotational movements of the axis 30 on itself, two movements of which are limited in amplitude so as to create a back and forth movement.
  • a first position illustrated on the figure 4a
  • the axis 30 is not driven in rotation by the motor 12
  • the evaporation chamber 5 is straight.
  • the notch 39 of the partition 40 is positioned on the upper part of the evaporation chamber 5 and the products are contained in the compartment delimited by the partition 40 .
  • a first movement of the motor 12 illustrated on figure 4b , drives the axis 30 on itself in a first direction of rotation with an angular displacement ⁇ 1 of between 5 ° and 90 °. This low-amplitude rotation does not allow the products placed in the compartment to migrate to the adjacent compartments because the height of the partition 40 is sufficient to contain the products.
  • a second movement of the motor 12 illustrated on figure 4c , drives the axis 30 on itself in a second direction of rotation, opposite to the first direction of rotation, with an angular displacement a2 substantially equal to the angular displacement of the first movement.
  • This low-amplitude rotation does not allow the products placed in the compartment to migrate to the adjacent compartments because the height of the partition 40 is sufficient to contain the products.
  • the back and forth movement thus corresponds to a swing of the axis 30 , that is to say a rotation of the axis 30 on itself in one direction then in the other.
  • a third movement of the motor 12 illustrated on figure 4d , drives the axis 30 on itself with an angle of rotation a3 between 90 ° and 180 °.
  • This large amplitude movement aims to allow the movement of the products between two consecutive compartments because the notch 39 of the partition 40 is arranged downwards.
  • the axis 30 can be arranged horizontally with respect to the cylindrical body of the chambers 5 , 10 .
  • the device advantageously comprises means for pivoting the axis in the vertical plane in order to guide the products placed in the evaporation chamber 5 between two consecutive compartments during the third movement.
  • the axis 30 can be mounted with a bias, that is to say inclined in the vertical plane, so as to guide the products against the partition 40 during the movement back and forth and between two consecutive compartments during large amplitude movement.
  • the partitions 40 are made of metal so as to conduct heat to the heart of the evaporation chamber 5 .
  • the freeze-drying process being particularly dependent on the temperature and pressure differences, the chambers 5 , 10 are preferably instrumented with temperature 20 , 24 and pressure 21 sensors.
  • an operator or an automatic device opens the lock 2a and the compartment between the locks 2a and 2b is placed under vacuum.
  • the sluice 2b is opened and products to be freeze-dried are thus introduced into the first compartment of the evaporation chamber 5 , for example products previously frozen.
  • the lock 2b is then closed and the lock 2a is opened once the vacuum has been established in the lock, so as to introduce new products into the loading chamber 41 .
  • the vacuum is initially carried out by opening the valve 7 and actuating the vacuum pump 6 .
  • the valve 7 remains open and the vacuum pump 6 continues to operate but the vacuum is essentially provided by the condensation of the vapor on the trap 11 .
  • the next step is to sublimate the water from the frozen products.
  • the frozen products are heated by the actuation of the heating means 15 , 16 of the evaporation chamber 5 and the actuation of the cooling means 17 , 18 of the condensation chamber 10 .
  • the temperature of the products in the evaporation chamber 5 is moved from -30 ° C to -25 ° C under a vacuum of 6.1 hPa.
  • the water from the frozen products is then sublimated and enters the condensation chamber 10 in the form of vapor where it is frozen and trapped in the condensation chamber 10 by the ice trap 11 , the temperature of which is preferably between - 50 ° C and -60 ° C.
  • the grid present at the level of the airlock 4 can prevent the dissemination of product particles if the evaporation rate is high.
  • the motor 12 drives the axis 30 in rotation according to the three movements described above.
  • the two back and forth movements are repeated alternately during a first cycle.
  • the motor 12 drives the axis 30 in rotation according to the third movement of great amplitude so as to move the products of the first compartment to the second compartment.
  • the lock 2b is opened and new products are introduced into the first compartment following the process described above.
  • the compartment between the locks 9a and 9b is under vacuum and the lock 9a is open and the lyophilized products are extracted from the evaporation chamber 5 by the discharge chamber 42 .
  • the lock 9a is then closed and the lock 9b is opened to extract the product through the outlet 8 .
  • the products are introduced into the vacuum put into the lock, then once the lock 9a is closed, the vacuum is broken and the pressure is brought by means of sterile nitrogen to the atmospheric pressure before opening lock 9b .
  • the lock 9b is closed and the vacuum is reestablished in the chamber 42 while awaiting the next loading.
  • the airlock valve 4 is closed and the heating 15 , 16 and cooling 17 , 18 means are stopped.
  • water vapor is introduced into the condensation chamber 10 through the steam injection nozzles 31 , 32 so as to cause the ice to melt and sterilize the ice.
  • the Figure 5 illustrates a third embodiment of the invention in which two condensation chambers 10a , 10b are connected to the evaporation chamber 5 by two separate locks 4a , 4b .
  • the two condensation chambers 10a , 10b are substantially identical and each present an ice trap 11a , 11b supplied by cooling means 17a , 17b , 18a , 18b as described with the first embodiment of the invention.
  • the implementation of two condensation chambers 10a , 10b makes it possible to regenerate one of the chambers while the other operates so as to extract the ice stored in the form of water.
  • the first chamber 10a is connected to the chamber 5 by opening the lock 4a while the second chamber 10b is not connected to the chamber 5 by closing the lock 4b .
  • the water in the form of ice is trapped in the first chamber 10a during the freeze-drying process.
  • the airlock 4b When the ice trap 11a of the first chamber 10a is substantially full, the airlock 4b is opened and then the airlock 4a is closed so as to use the second chamber 10b to trap the water vapor.
  • the first chamber 10a is depressurized and then steam is injected through the nozzle 32a so as to evacuate the water trapped in the form of ice. The first chamber 10a can then be reused when the ice trap 11b of the second chamber 10b is substantially full.
  • each recovery chamber 10a , 10b is connected to a vacuum pump 6a , 6b via a valve 7a , 7b.
  • a vacuum is placed in the recovery chamber 10a , 10b.
  • the valve 7a , 7b is opened without actuating the corresponding vacuum pump 6a , 6b so as to depressurize the condensation chamber 10a , 10b.
  • the injection of steam during the regeneration of a condensation chamber 10a , 10b also makes it possible to sterilize this condensation chamber 10a , 10b.
  • the partitions 40a , 40b have two distinct shapes mounted alternately in the evaporation chamber 5 .
  • the evaporation chamber 5 being cylindrical
  • the partitions 40a , 40b extend radially relative to the evaporation chamber 5 .
  • Each partition 40a , 40b is in the form of a disc, a portion of which forming substantially a quarter of the disc is removed so as to form a notch 39a , 39b .
  • Each notch 39a , 39b is intended to allow the passage of products between two consecutive compartments.
  • the notches 39a , 39b of two consecutive partitions 40a , 40b are offset axially with respect to the axis of revolution of the cylinder forming the evaporation chamber 5 , as illustrated in the figure. figure 6a when the motor 12 does not drive the evaporation chamber 5 in rotation.
  • the axial offset between the two notches 39a , 39b of two consecutive partitions 40a , 40b is approximately 90 °.
  • a first movement of strong amplitude illustrated on the figure 6d , induces an axial shift a3 between 90 ° and 180 ° to the right.
  • the first notch 39a of the first partition 40a is arranged on the left side while the second notch 39b of the second partition 40b is arranged on the lower part of the evaporation chamber 5 . It follows that the second partition 40b allows the passage of the product while the first partition 40a retains the products.
  • a second movement of strong amplitude illustrated on the figure 6e , induces an axial shift a4 of between 90 ° and 180 ° to the left.
  • the first notch 39a of the first partition 40a is disposed on the lower part of the evaporation chamber 5 while the second notch 39b of the second partition 40b is disposed on the left side. It follows that the first partition 40a allows the passage of the product while the second partition 40a retains the products.
  • a large amplitude movement is synchronized with the opening of the sluices 2b and 9a intended to allow the introduction and extraction of the products from the evaporation chamber 5 .
  • the invention thus makes it possible to lyophilize products placed in bulk in the evaporation chamber 5 and continuously, that is to say without stopping the heating means 15 , 16 and cooling 17 , 18 between two products to be lyophilized. .
  • the energy consumption of the freeze-drying device of the invention is reduced by 20 to 40% compared to the devices of the prior art for the same quantity of products.
  • the number of compartments is not limited. It allows to set the output frequency of the product. As every second compartment is used so as not to have any mixture in two consecutive compartments, the product outlet frequency is calculated as follows: if the product's residence time is 10 hours, with twenty compartments it is possible to remove all of them. hours a product charge. With forty compartments and a residence time of 10 hours, it is possible to reduce the output frequency every half hour.
  • the output frequency of the evaporator becomes a variable which depends on the number of compartments and the overall residence time in the evaporation chamber 5.
  • the residence time of the product in the freeze dryer can also depend on other factors such as size of pellets or granules entered and frequency of agitation movement.
  • the invention also makes it possible to lyophilize products in an automated and sterile manner since the operator does not have to make a physical connection at the level of the inlet 1 and the outlet 8 of the evaporation chamber 5 .
  • the invention has been implemented effectively with an evaporation chamber 5 , the capacity of which is between 0.01 and 1 m 3 .
  • an evaporation chamber 5 the capacity of which is between 0.01 and 1 m 3 .
  • the freeze-drying device can extract other solvents other than water, for example alcohol.

Landscapes

  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Drying Of Solid Materials (AREA)
  • Freezing, Cooling And Drying Of Foods (AREA)
  • Vaporization, Distillation, Condensation, Sublimation, And Cold Traps (AREA)
EP17719667.2A 2016-04-14 2017-04-10 Dispositif de sublimation et procédé de lyophilisation Active EP3443286B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR1653298A FR3050262B1 (fr) 2016-04-14 2016-04-14 Dispositif et procede de lyophilisation
FR1653297A FR3050261B1 (fr) 2016-04-14 2016-04-14 Dispositif et procede de lyophilisation
PCT/FR2017/050848 WO2017178740A1 (fr) 2016-04-14 2017-04-10 Dispositif et procede de lyophilisation

Publications (2)

Publication Number Publication Date
EP3443286A1 EP3443286A1 (fr) 2019-02-20
EP3443286B1 true EP3443286B1 (fr) 2021-01-27

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ID=58633024

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Application Number Title Priority Date Filing Date
EP17719667.2A Active EP3443286B1 (fr) 2016-04-14 2017-04-10 Dispositif de sublimation et procédé de lyophilisation

Country Status (7)

Country Link
US (1) US10627162B2 (zh)
EP (1) EP3443286B1 (zh)
JP (1) JP6894450B2 (zh)
CN (1) CN108885057B (zh)
CA (1) CA3057608C (zh)
IL (1) IL262182B (zh)
WO (1) WO2017178740A1 (zh)

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US20230122361A1 (en) * 2021-10-20 2023-04-20 DSM Sales & Manufacturing, Inc. Freeze-drying systems and methods
WO2023165937A1 (fr) * 2022-03-01 2023-09-07 Lyophitech Dispositif de lyophilisation

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US10497559B2 (en) * 2018-03-28 2019-12-03 Taiwan Semiconductor Manufacturing Company Ltd. Method for dehydrating semiconductor structure and dehydrating method of the same
US11828535B2 (en) * 2018-06-29 2023-11-28 Universiteit Gent Freezing, drying and/or freeze-drying of product dose units
JP2020028828A (ja) * 2018-08-21 2020-02-27 不二商事株式会社 使用済み紙おむつの処理装置および処理方法
CN110478928B (zh) * 2019-09-25 2024-04-16 北京师范大学 一种一次可准确定量浓缩多个样品的多旋转轴蒸发仪
TW202202792A (zh) * 2020-05-18 2022-01-16 日商Ｍｉｉ股份有限公司 真空凍結乾燥裝置及真空凍結乾燥方法
CN112158470B (zh) * 2020-11-30 2021-02-09 新三和（烟台）食品有限责任公司 一种带有干燥功能的食品储存装置
WO2022175999A1 (ja) * 2021-02-16 2022-08-25 株式会社アルバック 凍結乾燥装置、および凍結乾燥方法
CN113192719B (zh) * 2021-05-11 2022-05-20 英都斯特(无锡)感应科技有限公司 一种嵌入式冷冻冷藏保鲜及保藏弱磁场模块化装置
CN113340064A (zh) * 2021-05-27 2021-09-03 广东金城金素制药有限公司 一种乳糖酸红霉素的冻干机及其冻干工艺
JP7085088B1 (ja) * 2021-08-03 2022-06-16 株式会社エムアイアイ 凍結乾燥物

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US20230122361A1 (en) * 2021-10-20 2023-04-20 DSM Sales & Manufacturing, Inc. Freeze-drying systems and methods
WO2023165937A1 (fr) * 2022-03-01 2023-09-07 Lyophitech Dispositif de lyophilisation
FR3133228A1 (fr) * 2022-03-01 2023-09-08 Lyophitech Dispositif de lyophilisation

Also Published As

Publication number Publication date
WO2017178740A1 (fr) 2017-10-19
EP3443286A1 (fr) 2019-02-20
IL262182B (en) 2021-09-30
JP6894450B2 (ja) 2021-06-30
JP2019513969A (ja) 2019-05-30
CA3057608C (fr) 2024-02-13
CA3057608A1 (fr) 2017-10-19
US20190145705A1 (en) 2019-05-16
CN108885057B (zh) 2021-04-30
US10627162B2 (en) 2020-04-21
IL262182A (en) 2018-11-29
CN108885057A (zh) 2018-11-23

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