EP3093597B1 - Freeze drying plant - Google Patents

Description

TECHNICAL FIELD OF THE INVENTION

The invention relates to a freeze-drying plant. Furthermore, the invention relates to a method for controlling a freeze-drying plant.

STATE OF THE ART

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. Usually, such 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.

For the freeze-drying process, the drying material in the vials is first frozen in a product chamber of the freeze-dryer. In the following step, 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. In an ice condenser chamber connected to the product chamber, for example, on a cooled-down refrigeration cycle of the ice condenser chamber, 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. In the vials in the product chamber remains the final product of freeze-drying, which is referred to as lyophilisate.

Although all vials are (substantially) exposed to the same pressure and temperature, 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. For example, in the vials, 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. Ä.

"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.

In the case of freeze-drying, however, 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. Finally, electric fields have been used to standardize the freezing process.

• Das Auftreffen der Eiskristalle auf die Oberfläche des Trocknungsguts kann eine Erstarrung der Feuchtigkeit in den Vials zur Folge haben.
• Treten die Eiskristalle in das Innere der Vials und in das Trocknungsgut ein, können diese Eiskristalle stabile Keime für eine fortschreitende Eiskristallbildung in dem des Trocknungsgut bilden.
• Möglich ist auch, dass in den Vials oberhalb des Trocknungsguts angeordnetes, verdunstetes Lösungsmittel auf mit dem Gasstrom eintretende Eiskristalle trifft, womit eine Bildung von Eiskristallen aus dem verdunsteten Lösungsmittel erfolgt, so dass zu den Eiskristallen des Gasstromes weitere aus verdunstetem Lösungsmittel gebildete Eiskristalle hinzutreten, womit eine Art "selbstverstärkender Effekt" auftritt. Die sich derart vergrößernde Menge der Eiskristalle tritt dann in das Trocknungsgut ein, wo es dann zu einer vermehrten Ausbildung oder einem vermehrten Wachstum von Eiskristallen kommen kann.
• Ein Druckimpuls, ein Druckstoß und/oder eine Druckerhöhung kann eine Eiskristallbildung durch einen Gasstrom initiieren.

In order to ensure the simultaneous freezing of the material to be dried in all vials, the vials are also specifically exposed to a gas stream, which carries ice crystals with it. It has been found that exposing the vials to the ice crystals carried in the gas stream can result in immediate or short term freezing of the drying stock in all vials. It is believed that the instantaneous or short-term freezing thus produced is based on the following alternative or cumulative effects:

• The impact of the ice crystals on the surface of the drying material can result in a solidification of the moisture in the vials.
• If the ice crystals penetrate into the interior of the vials and into the material to be dried, these ice crystals can form stable nuclei for a progressive formation of ice crystals in the drying material.
• It is also possible that in the vials above the drying material arranged, evaporated solvent meets with the gas stream entering ice crystals, whereby a formation of ice crystals from the evaporated solvent, so that to the ice crystals of the gas stream further formed from evaporated solvent ice crystals, thus a kind of "self-reinforcing effect" occurs. The thus increasing amount of ice crystals then enters the Trocknungsgut, where it can then come to increased training or increased growth of ice crystals.
• A pressure pulse, a pressure surge and / or a pressure increase may initiate ice crystal formation by a gas flow.

From the prior art, the following methods for a so-called "controlled nucleation" (which is also referred to as "nucleation and which describes a process in which a first-order phase transition is initiated) are known:

According to the document WO 2011/034980 A1 It is proposed to introduce liquid nitrogen via a Venturi injector in the product chamber. In 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. Here, 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 use of foreign substances to stimulate nucleation is unfavorable under pharmaceutical conditions and requires extensive purification and sterilization.

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. By means of suitable cooling or heating devices, the gas can optionally be cooled or heated before being fed to the product chamber. Here, it is proposed to use an ice condenser chamber integrated in the freeze dryer or an external ice condenser chamber, whereby the product chamber and the ice condenser chamber can be separated from one another via an isolating valve. After placing the vials in the product chamber and closing and sealing the product chamber, the product chamber is pressurized with an inert gas such as argon, nitrogen or air. By actuating a pressurization circuit by the electronic control unit, 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. Following this, 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. Following this, a further cooling of the product chamber and the vials to about -40 ° C to -45 ° C take place. When this temperature is reached, a sufficient time is allowed for complete freezing to take place. This is followed by primary drying. Ultimately, 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. Here, 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. With the opening of a valve between the ice condenser chamber and the product chamber, the ice mist quickly passes from the ice condenser chamber to the product chamber due to the pressure differential, where the ice mist acts on the vials. During the production of the ice mist, the atmospheric pressure prevails in the ice condenser chamber, while in the product chamber a vacuum (for example 65 mbar) prevails. To generate the ice mist, 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. Furthermore, any additional required ice condenser chamber increases the cost and space requirements.

In principle, from the publication WO 2012/148372 A1 known embodiment proposes corresponding embodiment WO 2014/028119 A1 to produce frost condensed on an inner surface of the ice condenser chamber. Again, the pressure in the ice condenser chamber is greater than the pressure in the product chamber. By opening a valve disposed between the product chamber and the ice condenser chamber valve in the Ice condenser chamber generated a turbulent gas flow, which causes the condensed frost is broken into ice crystals. With the resulting flow from the ice condenser chamber into the product chamber, the generated ice crystals enter the product chamber where they urge the vials. The publication WO 2014/028119 A1 discloses all the features in the introductory part of claim 1. Further related art to a freeze dryer is off US 2 994 132 A known.

OBJECT OF THE INVENTION

• den Bauraumbedingungen,
• dem Bauaufwand,
• dem Steuerungsaufwand,
• einer Nachrüstbarkeit bestehender Gefriertrockner mit Erweiterung der Funktionalitäten und/oder
• der Anzahl der im Zuge des Gefriertrocknungsprozesses anzusteuernden Ventileinrichtungen

gewidmet ist. Darüber hinaus liegt der Erfindung die Aufgabe zugrunde, ein verbessertes Verfahren zur Steuerung einer entsprechenden Gefriertrocknungsanlage vorzuschlagen.The invention has for its object to provide a freeze-drying plant and / or a freeze dryer, which (r) allows a homogeneous freezing of the drying material in the plurality of containers or vials, with particular attention in particular

• the installation space conditions,
• the construction costs,
• the control effort,
• a retrofittability of existing freeze dryer with extension of the functionalities and / or
• the number of valve devices to be controlled in the course of the freeze-drying process

is dedicated. In addition, the invention has for its object to propose an improved method for controlling a corresponding freeze-drying plant.

SOLUTION

The object of the invention is achieved with the features of the independent claims. Further preferred embodiments according to the invention can be found in the dependent claims.

DESCRIPTION OF THE INVENTION

According to the invention, a freeze-drying plant is proposed, which has a product chamber. Products in the product chamber go through the freeze-drying process. For example, the products are vials with disposed therein Trocknungsgut. It is possible that the product chamber has a plurality of superposed shelves on which a plurality of vials can be arranged.

Furthermore, the freeze-drying plant according to the invention has an ice chamber. In the ice chamber ice crystals are available and / or produced. Basically, the preparation can be done in any way. For a possibility encompassed by the invention, 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. It is also possible that 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. In the ice chamber, 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.

• eine Flüssigkeitsleitung für eine Flüssigkeit, die dann zu dem unter Druck stehenden Gas siedet (insbesondere Flüssigstickstoff),
• eine unter Druck stehende Gasleitung oder eine Inertgasleitung,
• eine Gasflasche wie eine Inertgasflasche,
• einen Flüssigkeitsanschluss (insbesondere einen Anschluss für Flüssigstickstoff) oder
• einen Gasanschluss mit Druckbegrenzung.

In the freeze-drying plant according to the invention, a valve is used. This valve is located between a supply and the ice chamber. Here, the supply provides a gas under a pressure which is greater than the pressure in the product chamber, which in particular for the time of generation of the ice crystals in the ice chamber and immediately before the opening of the valve (as will be described below) applies. In the context of the invention, the stock may be formed with a kind of storage container, which has been previously filled with the fluid. The fluid may be immediately the pressurized gas. It is also possible that in the stock a liquid, in particular liquid nitrogen, is stored, which is converted by boiling in a pressurized gas, which is then used. In this case, any gas can be used, in particular an inert gas, for example nitrogen or argon. In the simplest case, the stock is about

• a liquid line for a liquid which then boils to the pressurized gas (especially liquid nitrogen),
• a pressurized gas line or an inert gas line,
• a gas bottle like an inert gas bottle,
• a liquid connection (in particular a connection for liquid nitrogen) or
• a gas connection with pressure limitation.

In this case, any gas can be used, in particular an inert gas such as, for example, nitrogen or argon.

According to the invention, 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. In extreme cases, 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. Here, 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.

In particular, 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.

On the other hand, according to the patents US 8,875,413 B2 and US 8,839,528 B2 bring about different process conditions (in particular temperatures and / or pressures) on the one hand in the product chamber and on the other hand in the ice chamber, while according to the invention, at least during the "Controlled Nucleation", interdependent process conditions in the product chamber and the ice chamber, thus u. U. the effort for the implementation of the "Controlled Nucleation" is reduced and / or defined process conditions can be brought about in a simpler manner.

It is entirely possible that in the freeze-drying plant according to the invention a 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.

For such an integrated design, it is quite possible that 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. For this embodiment, 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. In a preferred embodiment of the invention, however, 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 Eiskondensatorkammer 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.

Quite possible, however, is that the ice chamber is formed separately from the freeze dryer. In this case, 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. Here, 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.)

Another aspect of the invention is dedicated to the entrainment process of the ice crystals by the flowing gas. According to a proposal of the invention, 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. For example, 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. Also possible is 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. It is also possible that 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 ,

It is possible that 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. For a particular embodiment of the invention, 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. In this way, in carrying out the Controlled Nucleation, 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. It is also possible that, via the operation of the cooling and / or heating device, 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.

In principle, 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.

In the context of the invention, 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. Furthermore, 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. Finally, 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". If said connection for a supply or an ice chamber on the one hand and the control output for the valve on the other hand present at this freeze dryer, 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. Under certain circumstances, 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.

There are many possibilities for the process design and the design of the process conditions in the product chamber and / or the ice condenser chamber. For a particular method according to the invention, 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) is first jointly established in the product chamber and the ice chamber connected via the opening. and a temperature below the freezing point of the solvent of the drying material is brought about. In the ice chamber, 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. Then, 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.

It is possible here that, as mentioned above, 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.

Advantageous developments of the invention will become apparent from the claims, the description and the drawings. The advantages of features and of combinations of several features mentioned in the description are merely exemplary and can take effect alternatively or cumulatively, without the advantages having to be achieved by embodiments according to the invention. Without thereby altering the subject matter of the appended claims, as regards the disclosure of the original application documents and the patent, further features can be found in the drawings, in particular the illustrated geometries and the relative dimensions of several components and their relative arrangement and operative connection. The combination of features of different embodiments of the invention or of features of different claims is also possible deviating from the chosen relationships of the claims and is hereby stimulated. This also applies to those features which are shown in separate drawings or are mentioned in their description. These features can also be combined with features of different claims. Likewise, in the claims listed features for further embodiments of the invention can be omitted.

The features mentioned in the patent claims and the description are to be understood in terms of their number that exactly this number or a greater number than the said number is present, without requiring an explicit use of the adverb "at least". For example, when talking about an element, it should be understood that there is exactly one element, two elements or more elements. These features may be supplemented by other features or be the only characteristics that make up the product in question.

The reference numerals contained in the claims do not limit the scope of the objects protected by the claims. They are for the sole purpose of making the claims easier to understand.

BRIEF DESCRIPTION OF THE FIGURES

Fig. 1

zeigt stark schematisiert eine erste Ausführungsform einer Gefriertrocknungsanlage.

Fig. 2

zeigt stark schematisiert eine zweite Ausführungsform einer Gefriertrocknungsanlage.

In the following the invention will be further explained and described with reference to preferred embodiments shown in the figures.

Fig. 1

shows very schematically a first embodiment of a freeze-drying plant.

Fig. 2

shows very schematically a second embodiment of a freeze-drying plant.

DESCRIPTION OF THE FIGURES

Fig. 1 shows a freeze dryer 1 with a freeze dryer 2. The freeze dryer 2 has a product chamber 3. In the 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). Furthermore, an ice condenser chamber 7 is integrated in the freeze dryer 2. Thus, the product chamber 3 and the ice condenser chamber 7 are arranged in a common housing 8 of the freeze dryer 2. In the ice condenser chamber 7, a cooling device 9, here a cooling coil 10, is arranged. In the ice condenser chamber 7, sublimed solvent condenses on the cooling device 9 in the primary drying.

At the same time, the ice condenser chamber 7 is used as the ice chamber 11. In this, 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). But it is also possible that 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. In Fig. 1 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. For the method used according to the invention, 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. From the branch 22, 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".

• Zunächst werden die Vials 5 auf den Stellflächen 4 in dem Gefriertrockner 2 in der Produktkammer 3 angeordnet.
• Nach druckdichter Verschließung des Gefriertrockners 2 kann optional ein "Spülen" der Produktkammer 3 und der Eiskammer 11 mit einem inerten Gas, bspw. Stickstoff erfolgen.
• Dann wird durch Betrieb der Kühleinrichtung 9 die Temperatur in der Produktkammer 3 und der Eiskammer 11 unter die Gefriertemperatur des Trocknungsguts 6 abgesenkt, beispielsweise auf eine Temperatur im Bereich von -3°C bis -7°C. Hierbei kann auch eine niedrigere Temperatur (bspw. - 50°C bis -65°C) der Kühleinrichtung 9 und/oder der Ablagerungsfläche 20 erzeugt werden. Möglich ist, dass hierbei die Produktkammer 3 zumindest teilweise über die Kühleinrichtung 9 mit gekühlt wird. Des Weiteren wird sowohl in der Produktkammer 3 als auch in der Eiskammer 11 ein technisches Vakuum erzeugt, beispielsweise mit einem Druck von ca. 3 bis 20 mbar. Es kommt zur Verdampfung von Lösungsmittel aus dem Trocknungsgut 6 in den Vials 5. Das verdampfte Lösungsmittel gelangt durch die nicht fluiddicht geschlossenen Vials 5 durch die Öffnung 13 zu den Ablagerungsflächen 20 der Kühleinrichtung 9, wo Eiskristalle gebildet werden. Die Erzeugung des technischen Vakuums in der Produktkammer 3 und der Eiskammer 11 erfolgt durch Betätigung der Pumpe 30 mit geöffnetem Ventil 28 und geschlossenem Ventil 23.
• Dem Vorrat 16 wird (gleichzeitig oder anschließend an die zuvor genannten Verfahrensschritte) über den Anschluss 25 bei geöffnetem Ventil 26, aber geschlossenem Ventil 23 unter Druck stehendes Gas oder die Flüssigkeit, insbesondere der Flüssigstickstoff, zugeführt. Eine zusätzliche Druckerhöhung in dem Vorrat 16 kann durch Betrieb einer Pumpe erfolge. Sofern dies gewünscht ist, kann eine Kühlung des Gases in den Vorrat 16 durch Betrieb der Kühleinrichtung 24 erfolgen. Möglich ist auch, dass in dem Vorrat 16 ausschließlich der Atmosphärendruck wirkt, womit dennoch gegenüber dem Druck in der Produktkammer 3 und der Eiskammer 11 ein Überdruck in dem Vorrat 16 vorhanden ist. Ist in dem Vorrat 16 eine Flüssigkeit, insbesondere Flüssigstickstoff, angeordnet, so kann diese durch Betrieb der Heizeinrichtung 24 gezielt zum Sieden gebracht werden, womit das unter Druck stehende Gas zur Verfügung gestellt wird.
• Haben sich an den Ablagerungsflächen 20 hinreichende Eiskristalle abgelagert (oder befindet sich auf andersartig herbeigeführter Weise in der Eiskammer 11 eine hinreichende Zahl von Eiskristallen in einem Eisnebel) wird bei geschlossenem Ventil 28 das Ventil 23 geöffnet, wobei auch möglich ist, dass ausschließlich eine impulsartige Öffnung mit sukzessiver Schließung und eine Öffnungs-Zeitspanne von insbesondere lediglich 80 Millisekunden erfolgt, wird dann das Ventil 23 geöffnet. Infolge des Überdrucks in dem Vorrat 16 strömt das darin enthaltene Gas über das Ventil 23, die Verzweigung 22, die Leitung 21, den Anschluss 15 und das Strömungsführungselement 17 bzw. die Lanze 18 in die Eiskammer 11. Von der Austrittsöffnung 19 strömt das Gas entlang der Ablagerungsflächen 20, wo dieses die hieran abgelagerten Eiskristalle mitnimmt. Unter Umständen nimmt das Gas auf dem Strömungsweg auch Eiskristalle eines Eisnebels in der Eiskammer 11 mit. Das strömende Gas tritt mit den enthaltenen Eiskristallen durch die Öffnung 16 hindurch und verteilt sich in der Produktkammer 3 mit der Umströmung der auf den Stellflächen 4 angeordneten Vials 5. Es kommt infolge der impulsartigen Beaufschlagung der Vials 5 mit den Eiskristallen zu einer sofortigen oder kurzfristigen Ausbildung von Eiskristallen in dem Trocknungsgut. Hiermit ist die erfindungsgemäß angestrebte "Controlled Nucleation" mit einer möglichst schlagartigen Gefrierung des Trocknungsguts 6 abgeschlossen. Möglich ist, dass das Ventil 23 dauerhaft geöffnet bleibt oder nur kurz oder impulsartig geöffnet wird, bspw. mit einer Öffnungs-Zeitspanne von insbesondere weniger als 100 oder 80 Millisekunden.
• Hieran kann optional eine weitere Kühlphase anschließen, in welcher die Produktkammer 3 und die Eiskammer 11 mit einem Inertgas, insbesondere Stickstoff, belüftet werden und zumindest in der Produktkammer 3 eine niedrigere Temperatur, insbesondere im Bereich von -30°C bis -50°C, herbeigeführt wird.
• Im Anschluss hieran können beliebige an sich bekannte Verfahrensschritte Anwendung finden. Insbesondere erfolgt dann die Primärtrocknung mit der Sublimation des Trocknungsguts, wobei die sublimierende Feuchtigkeit dann durch die Öffnung 13 zu der Kühleinrichtung 9 übertreten kann, womit dann die Eiskammer 11 als "klassische" Eiskondensatorkammer 7 genutzt ist. Es können sich dann weitere Verfahrensschritte, insbesondere eine Sekundärtrocknung anschließen.

The use of the freeze dryer 1 for a "controlled nucleation" is as follows:

• First, the vials 5 are placed on the shelves 4 in the freeze dryer 2 in the product chamber 3.
• After pressure-tight closure of the freeze-dryer 2, an optional "flushing" of the product chamber 3 and the ice chamber 11 with an inert gas, for example nitrogen, can take place.
• Then, by operation of the cooling device 9, the temperature in the product chamber 3 and the ice chamber 11 is lowered below the freezing temperature of the product to be dried 6, for example to a temperature in the range of -3 ° C to -7 ° C. In this case, a lower temperature (for example. - 50 ° C to -65 ° C) of the cooling device 9 and / or the deposition surface 20 can be generated. It is possible that in this case the product chamber 3 is at least partially cooled by the cooling device 9 with. Furthermore, both in the product chamber 3 and in the ice chamber 11 a technical vacuum generated, for example, with a pressure of about 3 to 20 mbar. The evaporation of solvent from the drying material 6 in the vials 5 occurs. The vaporized solvent passes through the openings 12, which are not closed in a fluid-tight manner, to the deposition surfaces 20 of the cooling device 9, where ice crystals are formed. The generation of the technical vacuum in the product chamber 3 and the ice chamber 11 takes place by actuation of the pump 30 with the valve 28 open and the valve 23 closed.
• The supply 16 is supplied (simultaneously or subsequently to the aforementioned method steps) via the connection 25 with the valve 26 open, but the valve 23 is pressurized gas or the liquid, in particular the liquid nitrogen. An additional pressure increase in the reservoir 16 may be achieved by operation of a pump. If desired, cooling of the gas in the reservoir 16 may be accomplished by operation of the cooling device 24. It is also possible that in the supply 16 only the atmospheric pressure acts, which nevertheless over the pressure in the product chamber 3 and the ice chamber 11, an overpressure in the stock 16 is present. If a liquid, in particular liquid nitrogen, is arranged in the supply 16, then this can be deliberately boiled by operation of the heating device 24, thus making available the pressurized gas.
• If sufficient ice crystals have deposited on the deposition surfaces 20 (or if a sufficiently large number of ice crystals in an ice mist are present in an otherwise different manner in the ice chamber 11), the valve 23 is opened when the valve 28 is closed, whereby it is also possible to use only a pulse-like opening With successive closure and an opening period of in particular only 80 milliseconds, then the valve 23 is opened. Due to the overpressure in the reservoir 16, the gas contained therein flows via the valve 23, the branch 22, the conduit 21, the port 15 and the flow guide element 17 and the lance 18 into the ice chamber 11. From the outlet port 19, the gas flows along the deposition surfaces 20, where this entrains the deposited thereon ice crystals. Under certain circumstances, the gas also carries along the flow path ice crystals of an ice mist in the ice chamber 11. The flowing gas passes with the contained ice crystals through the opening 16 and distributed in the product chamber 3 with the flow around the arranged on the shelves 4 vials 5. It comes as a result of impulsive loading of the vials 5 with the ice crystals for an immediate or short-term formation of ice crystals in the Trocknungsgut. This concludes the "Controlled Nucleation" aimed at according to the invention with a possible sudden freezing of the dried material 6. It is possible for the valve 23 to remain permanently open or to be opened only briefly or in pulses, for example with an opening period of, in particular, less than 100 or 80 milliseconds.
• This can optionally be followed by another cooling phase in which the product chamber 3 and the ice chamber 11 are ventilated with an inert gas, in particular nitrogen, and at least in the product chamber 3 a lower temperature, in particular in the range of -30 ° C to -50 ° C, is brought about.
• Following this, any known process steps can be used. In particular, the primary drying then takes place with the sublimation of the material to be dried, wherein the subliming moisture can then pass through the opening 13 to the cooling device 9, whereby the ice chamber 11 is then used as a "classic" ice condenser chamber 7. It may then be followed by further process steps, in particular a secondary drying.

The control of the above-explained method steps is carried out by an electronic control unit 31. For the illustrated embodiment, 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.

• Mittels der Steuerleitung 32 steuert die Steuereinheit 31 die Pumpe 30 an, um in der Produktkammer 3 und der Eiskammer 11 ein technisches Vakuum zu erzeugen. Über die Steuerleitung 33 steuert die Steuereinheit 31 das Ventil 28 in seine Öffnungsstellung, um die gemeinsame Erzeugung des technischen Vakuums in der Produktkammer 3 und der Eiskammer 11 durch Betrieb der Pumpe 30 zu ermöglichen, und am Ende des Betriebs der Pumpe 30 und vor der Öffnung des Ventils 23 in seine Schließstellung, um die Verbindung mit der Pumpe 30 zu schließen. Über die Steuerleitung 34 schließt die Steuereinheit 31 das Ventil 23 während der Befüllung des Vorrats 16 und öffnet dieses, wenn die Zuführung des Gases 16 zu der Eiskammer 11 erforderlich ist. Mittels der Steuerleitung 35 steuert die Steuereinheit 31 das Ventil 26 in eine Öffnungsstellung, wenn Gas dem Vorrat 16 zugeführt werden soll, und in eine Schließstellung, wenn der Vorrat 16 hinreichend gefüllt ist. Mittels der Steuerleitung 36 steuert die Steuereinheit 31 die Kühleinrichtung 9 entsprechend der erforderlichen Kühlleistung an. Schließlich steuert die Steuereinheit 31 über die Steuerleitung 37 die Verschlusseinrichtung 14 derart an, dass während der erläuterten Verfahrensschritte die Verschlusseinrichtung 14 ihre Öffnungsstellung einnimmt mit freigegebener Öffnung 13 und Verbindung der Produktkammer 3 mit der Eiskondensatorkammer 7 / Eiskammer 11. Über eine weitere (hier nicht dargestellte) Steuerleitung kann die Steuereinheit 31 auch die Heiz- und/oder Kühleinrichtung 24 ansteuern.

The control unit 31 controls via the in Fig. 1 Dashed lines shown electrical control lines 32-37, the components of the freeze-drying plant 1 for performing the method as previously explained to:

• By means of the control line 32, the control unit 31 controls the pump 30 to generate a technical vacuum in the product chamber 3 and the ice chamber 11. Via the control line 33, the control unit 31 controls the valve 28 in its open position to allow the common generation of the technical vacuum in the product chamber 3 and the ice chamber 11 by operation of the pump 30, and at the end of the operation of the pump 30 and before Opening the valve 23 in its closed position to close the connection with the pump 30. Via the control line 34, the control unit 31 closes the valve 23 during the filling of the supply 16 and opens it when the supply of the gas 16 to the ice chamber 11 is required. By means of the control line 35, the control unit 31 controls the valve 26 in an open position when gas is to be supplied to the stock 16, and in a closed position when the stock 16 is sufficiently filled. By means of the control line 36, the control unit 31 controls the cooling device 9 according to the required cooling capacity. Finally, the control unit 31 controls the closure device 14 via the control line 37 in such a way that the closure device 14 assumes its open position with the opening 13 released and the product chamber 3 is connected to the ice condenser chamber 7 / ice chamber 11 via a further (not shown here) ) Control line 31, the control unit 31 and the heating and / or cooling device 24 to control.

At the in Fig. 2 illustrated embodiment of the freeze dryer 1, the freeze dryer 2 is basically the same Fig. 1 and the associated description. However, here the ice condenser chamber 7 is not additionally used as an ice chamber 11. Furthermore, 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".

• Nach Einbringung der Vials 5 mit dem Trocknungsgut in die Produktkammer 3 und dichter Verschließung des Gefriertrockners 2 erfolgt (ggf. nach einer Spülung der Produktkammer 3, der Eiskondensatorkammer 7 und/oder der Eiskammer 11 mit einem inerten Gas wie Stickstoff) die gemeinsame Erzeugung eines technischen Vakuums (bspw. im Bereich von 5 bis 20 mbar) sowohl in der Produktkammer 3 als auch in der Eiskammer 11. Hierzu ist das Ventil 23 geschlossen, während bei geöffnetem Ventil 42 der Betrieb der Pumpe 30 erfolgt. Das in der Produktkammer 3, der Leitung 39 und der Eiskammer 11 angeordnete Gas wird somit über die Pumpe 30 evakuiert.
• Infolge des technischen Vakuums in der Produktkammer 3 und einer Temperatur unterhalb der Gefriertemperatur in der Produktkammer 3 (bspw. -5°C) kommt es zu einer Verdunstung des Lösungsmittels in dem Trocknungsgut 6. Dieses verdunstete Lösungsmittel gelangt über den Anschluss 38 und die Leitung 39 in die Eiskammer 11, wo sich das verdunstete Lösungsmittel als Eiskristalle an Ablagerungsflächen 20 einer in der Eiskammer 11 angeordneten Kühleinrichtung 9 ablagert. Hierbei kann die Temperatur der Kühleinrichtung 9 oder der Ablagerungsfläche 20 im Bereich von -30 bis -40°C liegen.
• Nach Schließung des Ventils 42 wird dann das Ventil 23 geöffnet. Gas des Vorrats 16 mit Atmosphärendruck oder einem anderen Druck oberhalb des technischen Vakuums in der Produktkammer 3 und der Eiskammer 11 gelangt über den Anschluss 43 in die Eiskammer 11. Das Gas strömt entlang der Ablagerungsflächen 20 und nimmt von dieser Eiskristalle mit. Das Gas gelangt dann durch die Leitung 39 in die Produktkammer 3, wo das Gas mit darin mitgeführten Eiskristallen die Vials 5 beaufschlagt und es zu der "Controlled Nucleation" kommt.
• Hieran anschließend können an sich bekannte Verfahrensschritte für die Gefriertrocknung, insbesondere ein weiteres Gefrieren wie für die Ausführungsform gemäß Fig. 1 beschrieben, eine Primärtrocknung mit dem sublimierenden Lösungsmittel und eine Sekundärtrocknung, durchgeführt werden.

The freezing of the drying material 6 is carried out for the freeze-drying plant 1 according to Fig. 2 as follows:

• After introduction of the vials 5 with the material to be dried in the product chamber 3 and tight closure of the freeze dryer 2 takes place (possibly after flushing the product chamber 3, the ice condenser chamber 7 and / or the ice chamber 11 with an inert gas such as nitrogen) the joint production of a technical Vacuum (eg. In the range of 5 to 20 mbar) both in the product chamber 3 and in the ice chamber 11. For this purpose, the valve 23 is closed, while the valve 42 is open, the operation of the pump 30. The gas arranged in the product chamber 3, the line 39 and the ice chamber 11 is thus evacuated via the pump 30.
• As a result of the technical vacuum in the product chamber 3 and a temperature below the freezing temperature in the product chamber 3 (for example. -5 ° C) there is an evaporation of the solvent in the Trocknungsgut 6. This evaporated solvent passes through the terminal 38 and the line 39th into the ice chamber 11, where the evaporated solvent deposits as ice crystals on deposition surfaces 20 of a cooling device 9 arranged in the ice chamber 11. Here, the temperature of the cooling device 9 or the deposition surface 20 may be in the range of -30 to -40 ° C.
• After closing the valve 42, the valve 23 is then opened. Gas of the reservoir 16 at atmospheric pressure or other pressure above the technical vacuum in the product chamber 3 and the ice chamber 11 passes through the port 43 into the ice chamber 11. The gas flows along the deposition surfaces 20 and carries with them ice crystals. The gas then passes through the line 39 into the product chamber 3, where the gas with ice crystals entrained therein, the vials 5 is applied and it comes to the "Controlled Nucleation".
• Thereafter, known per se for process steps for freeze-drying, in particular a further freezing as for the embodiment according to Fig. 1 described a primary drying with the subliming solvent and a secondary drying can be performed.

Again, the control of the process by a control unit 31 via the control line 32, the control unit 31 controls the pump 30, while the control lines 33, 35 of the control of the valve 42 and 23 are used.

To give only an example, 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.

In the ice condenser chamber 7, temperatures in the range of -100 ° C to -50 ° C are preferably achieved.

Of interest may be under circumstances to retrofit a conventional freeze-drying plant and to improve or expand the operation, which can be done later after delivery of the conventional freeze-drying plant to the customer, sometimes only after many years, or at the factory, so that optional the distribution of the conventional freeze-drying plant or the retrofitted freeze-drying plant can be done. 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.

1. a) Möglich ist, dass über die Nachrüsteinheit oder den Nachrüstsatz mit dem Nukleator-Zusatzbehälter sowohl das über Druck stehende Gas als auch die mit dem strömenden Gas mitgeführten Eiskristalle bereitgestellt wird. In diesem Fall bildet der Nukleator-Zusatzbehälter eine Eiskammer, in welcher die Eiskristalle (außerhalb des herkömmlichen Gefriertrockners) gebildet werden. Vorzugsweise dient dann die Eiskammer auch der Aufnahme des unter Druck stehenden Gases. Zur Herbeiführung der "Controlled Nucleation" wird in diesem Fall der Nukleator-Zusatzbehälter mit dem herkömmlichen Gefriertrockner verbunden und das unter Druck stehende Gas mit den mitgeführten Eiskristallen wird durch die Produktkammer unter Beaufschlagung der Produkte geleitet, was auch mit einer Durchleitung durch die Kondensatorkammer erfolgen kann.
2. b) Für eine alternative Ausgestaltung wird ausgenutzt, dass in der Kondensatorkammer eines herkömmlichen Gefriertrockners unter Umständen bereits eine Kühleinrichtung vorhanden ist. Diese kann multifunktional genutzt werden, in dem die Kondensatorkammer gleichzeitig als Eiskammer genutzt wird, so dass hierin die von dem Gas mitgeführten Eiskristalle gebildet werden, die für die "Controlled Nucleation" genutzt werden. In diesem Fall bildet der Nukleator-Zusatzbehälter einen Vorrat, über welchen das unter Druck stehende Gas bereitgestellt wird. Sind in der dann als Eiskammer genutzten Kondensatorkammer die Eiskristalle gebildet, wird das Gas von dem Vorrat der Kondensatorkammer/Eiskammer zugeführt und unter Mitnahme der Eiskristalle gelangt das Gas in die Produktkammer, wo dieses mit den Eiskristallen die Produkte beaufschlagt.

There are two different embodiments, if a retrofit of a conventional freeze dryer is to take place, which already has a product chamber and a condenser chamber:

1. a) It is possible that both the pressurized gas and the entrained with the flowing gas ice crystals is provided on the retrofit unit or the retrofit kit with the nucleator auxiliary tank. In this case, the nucleator auxiliary container forms an ice chamber in which the ice crystals (outside the conventional freeze dryer) are formed. Preferably, then the ice chamber also serves to receive the pressurized gas. In this case, to effect the controlled nucleation, the nucleator auxiliary tank is connected to the conventional freeze dryer and the gas under pressure is connected to the conventional freeze dryer entrained ice crystals is passed through the product chamber under exposure to the products, which can also be done with a passage through the condenser chamber.
2. b) For an alternative embodiment, use is made of the fact that a cooling device may already be present in the condenser chamber of a conventional freeze-dryer. This can be used multifunctional, in which the condenser chamber is used at the same time as an ice chamber, so that herein formed by the gas ice crystals are formed, which are used for the "Controlled Nucleation". In this case, the nucleator supplemental container forms a reservoir over which the pressurized gas is provided. If the ice crystals are formed in the condenser chamber then used as the ice chamber, the gas is supplied from the supply to the condenser chamber / ice chamber and, taking along the ice crystals, the gas passes into the product chamber, where it applies the ice crystals to the products.

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. 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. Thus, 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.

It is also possible that 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. In this case, it is also possible via one or the control unit to switch over at least one valve via which the freeze dryers are connected to the common ice chamber and / or the common supply.

LIST OF REFERENCE NUMBERS

1

Freeze drying plant

2

freeze dryer

3

product chamber

4

footprint

5

Vial

6

be dried

7

ice condenser

8th

casing

9

cooling device

10

cooling coil

11

ice chamber

12

intermediate wall

13

opening

14

closure device

15

connection

16

stock

17

Flow guide element

18

lance

19

outlet opening

20

deposition surface

21

fluidic line

22

branch

23

Valve

24

Heating and / or cooling device

25

connection

26

Valve

27

management

28

Valve

29

suction

30

pump

31

control unit

32

control line

33

control line

34

control line

35

control line

36

control line

37

control line

38

connection

39

fluidic line

40

opening

41

connection

42

Valve

43

connection

44

reservoir

45

Nucleator additional storage tank

Claims (13)

1. Freeze drying system (1) with

   a) a product chamber (3) wherein products run through a freeze drying process and

   b) an ice chamber (11) used for producing ice crystals,

   c) a valve (23) which is arranged between

   ca) a supply (16) which is able to provide a gas under a pressure which is higher than the pressure in the product chamber (3) and

   cb) the ice chamber (11),

   d) the supply (16), the valve (23), the ice chamber (11) and the product chamber (3) being arranged one behind the other in this sequence,

   e) and a control unit (31),

   characterised in that

   f) the control unit (31) comprises control logic which at a point in time at which

   fa) ice crystals are present in the ice chamber (11) and

   fb) the ice chamber (11) is connected via an opening (13) to the product chamber (3) produces a control signal which opens the valve (23) so that gas streams from the supply (16) through the valve (23) and through the ice chamber (11) taking along ice crystals into the product chamber (3).
2. Freeze drying system (1) of claim 1, characterised in that the ice chamber (11) is constructionally integrated into a freeze dryer (2).
3. Freeze drying system (1) of claim 2, characterised in that the ice chamber (11) is formed by an ice condenser chamber (7) of the freeze dryer (2).
4. Freeze drying system (1) of claim 1, characterised in that

   a) the ice chamber (11) is formed separately from the freeze dryer (2) and

   b) the ice chamber (11) is connected via a line (39) to a port (38) of the freeze dryer (2) to the freeze dryer (2), the port (38) opening into the product chamber (3) or ice condenser chamber (7).
5. Freeze drying system (1) of one of the preceding claims, characterised in that a guiding element (17) for the stream of gas is provided in the ice chamber (11) or in the ice condenser chamber (7), the guiding element (17) guiding and/or redirecting gas which is provided by the supply (16) towards deposition surfaces (20) for ice crystals.
6. Freeze drying system (1) of one of the preceding claims, characterised in that the supply (16) comprises a supply reservoir (44).
7. Freeze drying system (1) of claim 6, characterised in that the supply reservoir (44) comprises a heating and/or cooling device (24) for heating and/or cooling the pressurized fluid in the supply reservoir (44).
8. Freeze drying system (1) of one of the preceding claims, characterised in that the supply (16) comprises liquid nitrogen.
9. Method for controlling a freeze drying system (1) of one of claims 1 to 8, wherein

   a) in the product chamber (3) and in the ice chamber (11) connected to the product chamber (3) by the opening (13) at the same time a technical vacuum and a temperature below the freezing temperature of the product (6) which is to be dried is induced,

   characterised in that

   b) in the ice chamber (11) ice crystals are produced from evaporated solvent of the product (6) which is to be dried and

   c) a valve (23) arranged between a supply (16) which provides a pressurised gas, the pressure of the provided gas being higher than the pressure in the product chamber (3) and in the ice chamber (11), and the ice chamber (11) is opened so that gas streams from the supply (16) through the valve (23) and through the ice chamber (11) taking along ice crystals into the product chamber (3).
10. Method of claim 9, characterised in that the fluid in the supply (16) is cooled and/or heated by a heating and/or cooling device (24).
11. Method of one of claims 9 and 10, characterised in that in the region of the ice crystals the gas is guided and/or redirected by a guiding element (17) for the stream of the gas.
12. Method of one of claims 9 to 11, characterised in that ice crystals are deposited in the ice chamber (11) at deposit surfaces (20).
13. Method of one of claims 9 to 12, characterised in that an ice fog comprising ice crystals is produced in the ice chamber (11).

Images