EP0301117B1 - Freeze-drying apparatus - Google Patents

Freeze-drying apparatus Download PDF

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Publication number
EP0301117B1
EP0301117B1 EP87110955A EP87110955A EP0301117B1 EP 0301117 B1 EP0301117 B1 EP 0301117B1 EP 87110955 A EP87110955 A EP 87110955A EP 87110955 A EP87110955 A EP 87110955A EP 0301117 B1 EP0301117 B1 EP 0301117B1
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EP
European Patent Office
Prior art keywords
valve
chamber
condensation surface
condensor
freeze
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
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EP87110955A
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German (de)
French (fr)
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EP0301117A1 (en
Inventor
Heinrich Steinkamp
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GEA Lyophil GmbH
Original Assignee
Finn Aqua Santasalo Sohlberg GmbH
Amsco Finn Aqua GmbH
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Application filed by Finn Aqua Santasalo Sohlberg GmbH, Amsco Finn Aqua GmbH filed Critical Finn Aqua Santasalo Sohlberg GmbH
Priority to EP87110955A priority Critical patent/EP0301117B1/en
Priority to ES87110955T priority patent/ES2068809T3/en
Priority to DE3750847T priority patent/DE3750847D1/en
Priority to JP63173852A priority patent/JP2676374B2/en
Priority to US07/226,536 priority patent/US4949473A/en
Publication of EP0301117A1 publication Critical patent/EP0301117A1/en
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Publication of EP0301117B1 publication Critical patent/EP0301117B1/en
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    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F26—DRYING
    • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
    • F26B5/00—Drying solid materials or objects by processes not involving the application of heat
    • F26B5/04—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum
    • F26B5/06—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing

Definitions

  • the present invention relates to a device for freeze drying with an evacuable chamber and an evacuation system.
  • Freeze drying is primarily used to preserve temperature-sensitive products, the properties of which should be retained. Freeze-drying is mainly used in the fields of pharmacy, biology and medicine.
  • the usual freeze-drying process takes place approximately as follows: after freezing the product containing water, the sublimation of the water present in ice form takes place under vacuum (about 10 perennial1 mbar). After this main drying, the post-drying takes place, during which the adsorptively bound moisture is removed in order to achieve extremely low residual moisture. During the final drying, the product is warmed up in compliance with permissible temperature limits. The pressure at which post-drying takes place is around 10 ⁇ 3 mbar.
  • the prior art also includes the content of US-A-40 60 400.
  • This document discloses a truck with a cooling container and a refrigerator. Food is transported in the truck's cooling container at normal pressure. In the event of special temperature conditions or if the chiller fails liquid nitrogen is sprayed into the cooling container.
  • the present invention has for its object to provide a freeze-drying device of the type mentioned, in which the product batches are no longer at risk from accidents of the type described or a similar type.
  • the valve between the further condensation surface in the condenser and the storage container is opened, so that the refrigerant flows into the condensation surface.
  • the further condensation surface thus takes over the pumping effect.
  • the vacuum in the freeze-drying chamber remains independent of the equipment so that there is no risk of thawing or thawing of the product.
  • the additional condensation surface can be accommodated in the freeze-drying chamber, in the condenser which is usually connected to the freeze-drying chamber or in a separate chamber.
  • the device for freeze drying shown in the figure comprises the vacuum chamber 1 with the shelves 2 on which the product is located during the course of the freeze drying process.
  • the shelves 2 are usually both coolable and heatable.
  • the shelves 2 are equipped with cavities, not shown in detail, through which a temperature control agent (for example silicone oil) flows.
  • the temperature control circuit is shown in dash-dotted lines and labeled 3.
  • the setting plates 2 are parallel to each other and the feed pump 4 is switched on. If the circulating refrigerant is to be cooled, then the compressor refrigeration machine 5 is started up.
  • the compressor refrigeration machine 5 is located in the refrigerant circuit 6, which usually comprises the water-cooled condenser 7, the heat exchanger 8 and the valve 9.
  • the condenser 7 is preferably water-cooled.
  • the heat exchanger 8 is in the Temperature control circuit 3 switched on. Often, several compressor chillers are used at this point to either ensure operation (separate circuits) or to reach lower temperatures (cascade connection). It is also possible to use another chiller (for example an adsorption chiller).
  • the heating of the setting plates 2 is usually carried out by means of an electrical heating, not shown in detail, of the temperature control medium circulating in the temperature control circuit 3.
  • an electrical heating not shown in detail
  • the use of waste heat from the chillers or the use of steam-heated heat exchangers is also possible.
  • An evacuation system 11 is connected to the vacuum chamber 1 and comprises a condenser 12 and a vacuum pump 13 (gas ballast pump).
  • the valve 15 is located in the connecting line 14 between the vacuum chamber 1 and the condenser 12.
  • the line 16 with the valve 17 extends between the condenser 12 and the vacuum pump 13.
  • condensation surfaces 18 are accommodated within the condenser 12 and serve to remove water vapor from the chamber 1 during normal operation of the freeze-drying system.
  • the condensation surfaces usually consist of coils through which the refrigerant (for example chlorofluorocarbons) flows. The outer surfaces of these coils form the actual condensation surfaces.
  • the compressor refrigeration machine 5 also serves to supply the condensation surfaces 18 with refrigerant.
  • the condensation surfaces 18 can be connected to the refrigerant circuit 6 via the lines 19 and 21 with the valve 22.
  • the storage container 26 contains a low-boiling refrigerant 27, for example liquid nitrogen.
  • the line 28 is connected to the lower region of the storage container 26, which opens into its upper region above the refrigerant level.
  • an evaporator 29 and a pressure control valve 31 are switched on. With the aid of these elements, a certain pressure, for example a few bar, preferably 3 bar, can be maintained within the storage container 26.
  • An alternative in which the further condensation surface is located inside the chamber 1 is shown in dashed lines. The connected via the valve 25 to the reservoir 26 line 24 'opens into the condensation surface 23', which is arranged next to the adjusting plates 2.
  • the freeze-drying device shown works as follows: After a sterilization process, the product is introduced into the chamber 1 and frozen. For this purpose, the temperature control medium flowing in the temperature control circuit 3 is brought to correspondingly low temperatures with the aid of the compressor refrigerator 5. The valve 15 is closed during the freezing phase.
  • valves 15 and 17 are opened and the temperature control medium flowing in the temperature control circuit 3 is warmed up.
  • the valve 9 in the refrigerant circuit 6 is closed and the heating, not shown, is put into operation.
  • the chamber 1 is evacuated to a pressure of about 10 ⁇ 1 mbar.
  • the condensation surfaces 18 serve to remove the relatively large amounts of water vapor during normal operation, which are cooled with the aid of the compressor refrigerator 5. Small amounts of permanent gases still present flow through the condenser 12 and are removed using the gas ballast pump 13.
  • the cooling for the condensation surfaces 18 fails.
  • the pumping speed for water vapor decreases and returns to 0 relatively quickly.
  • the water vapor escaping from the product is no longer removed. Since the temperature control medium in the temperature control circuit 3 is warm during the main and post-drying (room temperature or slightly above), the product on the setting plates 2 begins to heat up immediately. If the product thaws or thaws, there is often a loss of quality or even a change that renders the product unusable.
  • the condensation surface 23 is provided in the condenser 12.
  • the low-boiling refrigerant 27 enters the tube coil forming the condensation surface 23 from below, evaporates there and thus cools the condensation surface 23 very quickly to relatively low temperatures.
  • the evaporated refrigerant is discharged into the atmosphere via line 32, for example.
  • the condensation surface 23 takes effect before the water vapor absorbency of the condensation surfaces 18 has significantly decreased.
  • the water vapor suction capacity of the condenser 12 is thus retained regardless of the operating medium, and that is until the refrigerant is finally used up in the storage container 26.
  • the emergency cooling can therefore be maintained for a sufficiently long time in order to be able to remedy the incident that has occurred.
  • valve 15 When an accident occurs, the valve 15 must keep its open position, close the valve 17 and open the valve 25.
  • these valves are therefore equipped with electrical or electropneumatic actuators which are designed such that the valves 15 and 25 assume their open position in the event of a power failure and the valve 17 in its closed position in the event of a power failure. This ensures a safe function of the emergency cooling device.
  • valve 25 also opens in the event of a fault, while valve 15 closes.
  • the refrigerant 27 flows via line 24 'into the condensation surface 23', evaporates there and is discharged via line 32 'into the atmosphere.
  • the condensation surface 23 ' is sufficiently cold to maintain the vacuum in the chamber 1. The product batch contained therein is therefore not endangered.

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  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Drying Of Solid Materials (AREA)

Description

Die vorliegende Erfindung bezieht sich auf eine Einrichtung zur Gefriertrocknung mit einer evakuierbaren Kammer und einem Evakuierungssystem.The present invention relates to a device for freeze drying with an evacuable chamber and an evacuation system.

Die Gefriertrocknung wird in erster Linie zur Konservierung temperaturempfindlicher Produkte eingesetzt, deren Eigenschaften erhalten bleiben sollen. In den bereichen Pharmazie, Biologie und Medizin findet die Gefriertrocknung ihr Hauptanwendungsgebiet.Freeze drying is primarily used to preserve temperature-sensitive products, the properties of which should be retained. Freeze-drying is mainly used in the fields of pharmacy, biology and medicine.

Der übliche Gefriertrocknungsprozeß läuft etwa folgendermaßen ab: Nach dem Einfrieren des Wasser enthaltenden Produktes findet die Sublimation des in Eisform vorliegenden Wassers statt, und zwar unter vakuum (etwa 10⁻¹ mbar). Nach dieser Haupttrocknung findet die Nachtrocknung statt, während der die adsorptiv gebundene Feuchtigkeit entfernt wird, um extrem niedrige Restfeuchten zu erzielen. Während der Nachtrocknung wird das Produkt unter Einhaltung zulässiger Temperaturgrenzen erwärmt. Der Druck, bei dem die Nachtrocknung stattfindet, liegt bei etwa 10⁻³ mbar.The usual freeze-drying process takes place approximately as follows: after freezing the product containing water, the sublimation of the water present in ice form takes place under vacuum (about 10 etwa¹ mbar). After this main drying, the post-drying takes place, during which the adsorptively bound moisture is removed in order to achieve extremely low residual moisture. During the final drying, the product is warmed up in compliance with permissible temperature limits. The pressure at which post-drying takes place is around 10⁻³ mbar.

Da die Gefriertrocknung im Chargenbetrieb durchgeführt wird, ist man bemüht, die Chargen möglichst groß zu wählen. Entsprechend hoch ist dann auch der Wert der Chargen. Es ist inzwischen durchaus üblich, mit Chargen zu fahren, deren Wert über 100 TDM liegt. Der Verlust der Charge infolge eines Störfalles führt deshalb zu empfindlichen Verlusten.Since freeze drying is carried out in batch operation, efforts are made to choose the batches as large as possible. The value of the batches is correspondingly high. It is now quite common to use batches with a value in excess of 100,000 DM. The loss of the batch as a result of an accident therefore leads to sensitive losses.

Folgende, eine Produktcharge gefährdende Störfälle können eintreten:

  • Ausfall der Verdichter-Kältemaschinen, die die Produktstellflächen in der Vakuumkammer und die Kondensationsflächen im Kondensator mit Kühlmittel versorgen; dabei kann der Kältemittelverdichter selbst defekt gehen oder ein Verlust des Kältemittels aus dem Kältekreislauf eintreten;
  • Stromausfall, komplett oder teilweise;
  • Ausfall der Kühlung der Verflüssiger im Kühlmittelkreislauf der Kältemittelverdichter, wenn zum Beispiel die Wasserversorgung ausfällt;
  • Ausfall der Anlagensteuerung.
The following accidents that endanger a product batch can occur:
  • Failure of the compressor chillers, which supply the product shelves in the vacuum chamber and the condensation surfaces in the condenser with coolant; the refrigerant compressor itself may fail or the refrigerant may be lost from the refrigeration cycle;
  • Power failure, complete or partial;
  • Failure of the cooling of the condensers in the coolant circuit of the refrigerant compressors if, for example, the water supply fails;
  • System control failure.

Sämtliche dieser angegebenen Störfälle haben einen Ausfall der Kondensatorkühlung und damit einen Ausfall der Pumpleistung des Evakuierungssytems zur Folge. Da dem zu trocknenden Produkt während der Trocknung die für die Sublimation des Wassers erforderliche Energie in Form von Wärme zugeführt werden muß, führt ein Ausfall des Evakuierungssystems zu einer Erwärmung des Produktes, da vom Produkt abgegebener Wasserdampf nicht mehr abgepumpt wird. Gleichzeitig mit einem Druckanstieg in der Gefriertrocknungskammer beginnt das Produkt aufzutauen. Dieser Vorgang führt insbesondere bei hochempfindlichen Medikamenten zu Qualitätsverlusten, unter Umständen zum Verlust der kompletten Gefriertrocknungscharge.All of these specified incidents result in a failure of the condenser cooling and thus a failure of the pumping capacity of the evacuation system. Since the product to be dried has to be supplied with the energy required for the sublimation of the water in the form of heat during the drying process, a failure of the evacuation system leads to heating of the product, since water vapor released by the product is no longer pumped off. At the same time as the pressure in the freeze drying chamber increases, the product begins to thaw. This process leads to a loss of quality, especially with highly sensitive medication, and possibly to the loss of the entire freeze-drying batch.

Aus der US-A-24 53 033 ist eine Gefriertrocknungseinrichtung mit einer Kammer, in der sich Stellflächen für das zu gefriertrocknende Produkt befinden, mit einem aus Kondensator und Vakuumpumpe bestehenden Evakuierungssystem sowie mit einer dreistufigen Kältemaschine bekannt. Im Kondensator befinden sich zwei der Evakuierung der Kammer dienende Kondensationsflächen, die auf unterschiedlichen Temperaturen gehalten werden. Beide Kondensationsflächen werden während des normalen Betriebs der Gefriertrocknungsanlage von der dreistufigen Kältemaschine mit Kühlmitteln versorgt. Maßnahmen zur Rettung einer Charge bei einem Störfall sind offenbart.From US-A-24 53 033 a freeze-drying device with a chamber in which there are shelves for the product to be freeze-dried, with an evacuation system consisting of a condenser and a vacuum pump, and with a three-stage refrigerator is known. In the condenser there are two condensation surfaces which serve to evacuate the chamber and which are kept at different temperatures will. Both condensation surfaces are supplied with coolants by the three-stage chiller during normal operation of the freeze dryer. Measures to save a batch in the event of an accident are disclosed.

Aus der DE-A-31 07 241 ist es bekannt, zur Versorgung des Kondensators, der der Evakuierung einer Gefriertrocknungskammer dient, mehrere Kältemaschinen einzusetzen. Eine der Kältemaschinen wird nur dann eingeschaltet ("stand by"), wenn Störfälle an den anderen Kältemaschinen auftreten. Eine derartige Lösung ist technisch aufwendig. Außerdem ist ihr Betriebsverhalten träge, wenn jedem der Kälteaggregate eine separate Kondensationsfläche zugeordnet ist. In kritischen Phasen des Gefriertrocknungsprozesses können Produkt-Qualitätsverluste bereits dann auftreten, wenn von der Betriebskondensationsfläche auf die Reservekondensationsfläche umgeschaltet wird. Die Reservekondensationsfläche hat nicht sofort ihre Betriebstemperatur, so daß ein unzulässig hoher Druckanstieg in der Kammer unvermeidlich ist. Schließlich kann die "stand by"-Kältemaschine bei einem Stromausfall oder bei einem Ausfall der Anlagensteuerung ihren Betrieb gar nicht erst aufnehmen.From DE-A-31 07 241 it is known to use several refrigeration machines to supply the condenser, which is used to evacuate a freeze-drying chamber. One of the chillers is only switched on ("stand by") if malfunctions occur on the other chillers. Such a solution is technically complex. In addition, their operating behavior is sluggish if a separate condensation surface is assigned to each of the cooling units. In critical phases of the freeze drying process, product quality losses can already occur when switching from the operating condensation surface to the reserve condensation surface. The reserve condensation surface does not immediately have its operating temperature, so that an inadmissibly high pressure rise in the chamber is inevitable. After all, the "stand by" chiller cannot even start operating in the event of a power failure or a failure of the system control.

Zum Stand der Technik gehört außerdem noch der Inhalt der US-A-40 60 400. Dieses Dokument offenbart einen Lastwagen mit einem Kühlbehälter und einer Kältemaschine. Im Kühlbehälter des Lastwagens werden Nahrungsmittel transportiert, und zwar bei Normaldruck. Bei besonderen Temperaturverhältnissen oder bei einem Ausfall der Kältemaschine wird flüssiger Stickstoff in den Kühlbehälter eingesprüht.The prior art also includes the content of US-A-40 60 400. This document discloses a truck with a cooling container and a refrigerator. Food is transported in the truck's cooling container at normal pressure. In the event of special temperature conditions or if the chiller fails liquid nitrogen is sprayed into the cooling container.

Der vorliegenden Erfindung liegt die Aufgabe zugrunde, eine Gefriertrocknungseinrichtung der eingangs genannten Art zu schaffen, bei der die Produktchargen nicht mehr durch Störfälle der beschriebenen oder einer ähnlichen Art gefährdet sind.The present invention has for its object to provide a freeze-drying device of the type mentioned, in which the product batches are no longer at risk from accidents of the type described or a similar type.

Erfindungsgemäß wird diese Aufgabe durch die Merkmale des Patentanspruchs 1 gelöst.According to the invention, this object is achieved by the features of patent claim 1.

Bei einem Störfall wird das Ventil zwischen der weiteren Kondensationsfläche im Kondensator und dem Vorratsbehälter geöffnet, so daß das Kältemittel in die Kondensationsfläche einströmt. Die weitere Kondensationsfläche übernimmt damit die Pumpwirkung. Das Vakuum in der Gefriertrocknungskammer bleibt betriebsmittelunabhängig erhalten, so daß die Gefahr des An- oder Auftauens des Produktes nicht besteht. Die zusätzliche Kondensationsfläche kann in der Gefriertrocknungskammer, in dem üblicherweise an die Gefriertrocknungskammer angeschlossenen Kondensator oder auch in einer separaten Kammer untergebracht sein.In the event of a malfunction, the valve between the further condensation surface in the condenser and the storage container is opened, so that the refrigerant flows into the condensation surface. The further condensation surface thus takes over the pumping effect. The vacuum in the freeze-drying chamber remains independent of the equipment so that there is no risk of thawing or thawing of the product. The additional condensation surface can be accommodated in the freeze-drying chamber, in the condenser which is usually connected to the freeze-drying chamber or in a separate chamber.

Weitere Vorteile und Einzelheiten der Erfindung sollen anhand eines in der Figur schematisch dargestellten Ausführungsbeispieles erläutert werden.Further advantages and details of the invention will be explained with reference to an exemplary embodiment shown schematically in the figure.

Die in der Figur dargestellte Einrichtung zur Gefriertrocknung umfaßt die Vakuumkammer 1 mit den Stellflächen 2, auf denen sich das Produkt während des Ablaufs des Gefriertrocknungsprozesses befindet. Üblicherweise sind die Stellflächen 2 sowohl kühlbar als auch aufheizbar. Dazu sind die Stellflächen 2 mit im einzelnen nicht dargestellten Hohlräumen ausgerüstet, die von einem Temperiermittel (zum Beispiel Silikonöl) durchströmt werden. Der Temperierkreislauf ist strichpunktiert eingezeichnet und mit 3 bezeichnet. In diesen Temperaturkreislauf 3 sind die Stellplatten 2 parallel zueinander und die Förderpumpe 4 eingeschaltet. Soll das umströmende Kältemittel gekühlt werden, dann wird die Verdichter-Kältemaschine 5 in Betrieb gesetzt. Die Verdichter-Kältemaschine 5 befindet sich im Kältemittelkreislauf 6, der üblicherweise den mit Wasser gekühlten Verflüssiger 7, den Wärmetauscher 8 und das Ventil 9 umfaßt. Der Verflüssiger 7 ist vorzugsweise wassergekühlt. Der Wärmetauscher 8 ist in den Temperierkreislauf 3 eingeschaltet. Häufig werden mehrere Verdichter-Kältemaschinen an dieser Stelle eingesetzt, um entweder den Betrieb zu sichern (getrennte Kreisläufe) oder tiefere Temperaturen zu erreichen (Kaskadenschaltung). Auch der Einsatz einer anderen Kältemaschine (zum Beispiel Adsorptionskältemaschine) ist möglich.The device for freeze drying shown in the figure comprises the vacuum chamber 1 with the shelves 2 on which the product is located during the course of the freeze drying process. The shelves 2 are usually both coolable and heatable. For this purpose, the shelves 2 are equipped with cavities, not shown in detail, through which a temperature control agent (for example silicone oil) flows. The temperature control circuit is shown in dash-dotted lines and labeled 3. In this temperature circuit 3, the setting plates 2 are parallel to each other and the feed pump 4 is switched on. If the circulating refrigerant is to be cooled, then the compressor refrigeration machine 5 is started up. The compressor refrigeration machine 5 is located in the refrigerant circuit 6, which usually comprises the water-cooled condenser 7, the heat exchanger 8 and the valve 9. The condenser 7 is preferably water-cooled. The heat exchanger 8 is in the Temperature control circuit 3 switched on. Often, several compressor chillers are used at this point to either ensure operation (separate circuits) or to reach lower temperatures (cascade connection). It is also possible to use another chiller (for example an adsorption chiller).

Die Erwärmung der Stellplatten 2 erfolgt üblicherweise mittels einer im einzelnen nicht dargestellten elektrischen Beheizung des im Temperierkreislauf 3 umlaufenden Temperiermittels. Auch die Verwendung der Abwärme der Kältemaschinen oder der Einsatz dampfbeheizter Wärmetauscher ist möglich.The heating of the setting plates 2 is usually carried out by means of an electrical heating, not shown in detail, of the temperature control medium circulating in the temperature control circuit 3. The use of waste heat from the chillers or the use of steam-heated heat exchangers is also possible.

An die Vakuumkammer 1 ist ein Evakuierungssystem 11 angeschlossen, das einen Kondensator 12 und eine Vakuumpumpe 13 (Gasballastpumpe) umfaßt. In der Verbindungsleitung 14 zwischen Vakuumkammer 1 und Kondensator 12 befindet sich das Ventil 15. Zwischen Kondensator 12 und Vakuumpumpe 13 erstreckt sich die Leitung 16 mit dem Ventil 17.An evacuation system 11 is connected to the vacuum chamber 1 and comprises a condenser 12 and a vacuum pump 13 (gas ballast pump). The valve 15 is located in the connecting line 14 between the vacuum chamber 1 and the condenser 12. The line 16 with the valve 17 extends between the condenser 12 and the vacuum pump 13.

Innerhalb des Kondensators 12 sind eine oder mehrere Kondensationsflächen 18 untergebracht, die während des Normalbetriebs der Gefriertrocknungsanlage der Entfernung von Wasserdampf aus der Kammer 1 dienen. Die Kondensationsflächen bestehen üblicherweise aus Rohrschlangen, die von dem Kältemittel (zum Beispiel Fluorchlorkohlenwasserstoffe) durchströmt sind. Die Außenflächen dieser Rohrschlangen bilden die eigentlichen Kondensationsflächen. Der Versorgung der Kondensationsflächen 18 mit Kältemittel dient ebenfalls die Verdichterkältemaschine 5. Über die Leitungen 19 und 21 mit dem Ventil 22 sind die Kondensationsflächen 18 an den Kältemittelkreislauf 6 anschließbar.One or more condensation surfaces 18 are accommodated within the condenser 12 and serve to remove water vapor from the chamber 1 during normal operation of the freeze-drying system. The condensation surfaces usually consist of coils through which the refrigerant (for example chlorofluorocarbons) flows. The outer surfaces of these coils form the actual condensation surfaces. The compressor refrigeration machine 5 also serves to supply the condensation surfaces 18 with refrigerant. The condensation surfaces 18 can be connected to the refrigerant circuit 6 via the lines 19 and 21 with the valve 22.

Im Kondensator 12 befindet sich eine weitere Kondensationsfläche 23, die über die Leitung 24 mit dem Ventil 25 an den unteren Bereich eines Vorratsbehälters 26 angeschlossen ist. Der Vorratsbehälter 26.enthält ein niedrigsiedendes Kältemittel 27, beispielsweise flüssigen Stickstoff. Weiterhin ist an den unteren Bereich des Vorratsbehälters 26 die Leitung 28 angeschlossen, die in seinen oberen Bereich oberhalb des Kältemittelspiegels mündet. In dieser Leitung sind ein Verdampfer 29 und ein Druckregelventil 31 eingeschaltet. Mit Hilfe dieser Elemente kann innerhalb des Vorratsbehälters 26 ein bestimmter Druck, beispielsweise einige Bar, vorzugsweise 3 bar, aufrechterhalten werden. Eine Alternative, bei der sich die weitere Kondensationsfläche innerhalb der Kammer 1 befindet, ist gestrichelt dargestellt. Die über das Ventil 25 mit dem Vorratsbehälter 26 verbundene Leitung 24′ mündet in die Kondensationsfläche 23′, die neben den Stellplatten 2 angeordnet ist.There is a further condensation surface 23 in the condenser 12, which is connected via the line 24 with the valve 25 to the lower region of a storage container 26. The storage container 26 contains a low-boiling refrigerant 27, for example liquid nitrogen. Furthermore, the line 28 is connected to the lower region of the storage container 26, which opens into its upper region above the refrigerant level. In this line, an evaporator 29 and a pressure control valve 31 are switched on. With the aid of these elements, a certain pressure, for example a few bar, preferably 3 bar, can be maintained within the storage container 26. An alternative in which the further condensation surface is located inside the chamber 1 is shown in dashed lines. The connected via the valve 25 to the reservoir 26 line 24 'opens into the condensation surface 23', which is arranged next to the adjusting plates 2.

Die dargestellte Gefriertrocknungseinrichtung arbeitet folgendermaßen: Nach einem Sterilisationsvorgang wird das Produkt in die Kammer 1 eingebracht und eingefroren. Dazu wird das im Temperierkreislauf 3 strömende Temperiermittel mit Hilfe der Verdichter-Kältemaschine 5 auf entsprechend niedrige Temperaturen gebracht. Das Ventil 15 ist während der Einfrierphase geschlossen.The freeze-drying device shown works as follows: After a sterilization process, the product is introduced into the chamber 1 and frozen. For this purpose, the temperature control medium flowing in the temperature control circuit 3 is brought to correspondingly low temperatures with the aid of the compressor refrigerator 5. The valve 15 is closed during the freezing phase.

Zur Durchführung der Haupttrocknung werden die Ventile 15 und 17 geöffnet und das im Temperierkreislauf 3 strömende Temperiermittel aufgewärmt. Dazu wird das Ventil 9 im Kältemittelkreislauf 6 geschlossen und die nicht dargestellte Beheizung in Betrieb gesetzt.To carry out the main drying, the valves 15 and 17 are opened and the temperature control medium flowing in the temperature control circuit 3 is warmed up. For this purpose, the valve 9 in the refrigerant circuit 6 is closed and the heating, not shown, is put into operation.

Die Kammer 1 wird auf einen Druck von etwa 10⁻¹ mbar evakuiert. Der Entfernung der relativ großen Wasserdampfmengen dienen bei Normalbetrieb die Kondensationsflächen 18, die mit Hilfe der Verdichter-Kältemaschine 5 gekühlt werden. Geringe Mengen noch vorhandener Permanentgase durchströmen den Kondensator 12 und werden mit Hilfe der Gasballastpumpe 13 entfernt.The chamber 1 is evacuated to a pressure of about 10⁻¹ mbar. The condensation surfaces 18 serve to remove the relatively large amounts of water vapor during normal operation, which are cooled with the aid of the compressor refrigerator 5. Small amounts of permanent gases still present flow through the condenser 12 and are removed using the gas ballast pump 13.

Tritt einer der eingangs beschriebenen Störfälle ein, dann fällt die Kühlung für die Kondensationsflächen 18 aus. Das Saugvermögen für Wasserdampf nimmt ab und geht relativ schnell auf 0 zurück. Der aus dem Produkt entweichende Wasserdampf wird nicht mehr abgeführt. Da das Temperiermittel im Temperierkreislauf 3 während der Haupt- und der Nachtrocknung warm ist (Zimmertemperatur oder etwas darüber), beginnt sofort eine Erwärmung des auf den Stellplatten 2 befindlichen Produktes. Taut das Produkt an oder auf, tritt häufig ein Qualitätsverlust oder gar eine Veränderung ein, durch die das Produkt unbrauchbar wird.If one of the malfunctions described at the outset occurs, then the cooling for the condensation surfaces 18 fails. The pumping speed for water vapor decreases and returns to 0 relatively quickly. The water vapor escaping from the product is no longer removed. Since the temperature control medium in the temperature control circuit 3 is warm during the main and post-drying (room temperature or slightly above), the product on the setting plates 2 begins to heat up immediately. If the product thaws or thaws, there is often a loss of quality or even a change that renders the product unusable.

Um bei einem Störfall dieser Art das Wasserpumpsaugvermögen des Kondensators 12 betriebsmittelunabhängig, das heißt, unabhängig von den beim Normalbetrieb der Gefriertrocknungsanlage erforderlichen Mittel wie Strom, Wasser und dergleichen, aufrechterhalten zu können, ist im Kondensator 12 die Kondensationsfläche 23 vorgesehen. Durch Öffnen des Ventils 25 gelangt das niedrigsiedende Kältemittel 27 von unten in die die Kondensationsfläche 23 bildende Rohrschlange, verdampft dort und kühlt damit die Kondensationsfläche 23 sehr schnell auf relativ tiefe Temperaturen ab. Das verdampfte Kältemittel wird über die Leitung 32 zum Beispiel in die Atmosphäre abgeführt. Die Kondensationsfläche 23 wird wirksam, bevor das Wasserdampfsaugvermögen der Kondensationsflächen 18 maßgeblich abgenommen hat. Das Wasserdampfsaugvermögen des Kondensators 12 bleibt damit betriebsmittelunabhängig erhalten, und zwar bis zum endgültigen Verbrauch des Kältemittels im Vorratsbehälter 26.In order to be able to maintain the water pumping capacity of the condenser 12 independently of the operating medium in the event of a malfunction of this type, that is to say independent of the means such as electricity, water and the like required during normal operation of the freeze drying system, the condensation surface 23 is provided in the condenser 12. By opening the valve 25, the low-boiling refrigerant 27 enters the tube coil forming the condensation surface 23 from below, evaporates there and thus cools the condensation surface 23 very quickly to relatively low temperatures. The evaporated refrigerant is discharged into the atmosphere via line 32, for example. The condensation surface 23 takes effect before the water vapor absorbency of the condensation surfaces 18 has significantly decreased. The water vapor suction capacity of the condenser 12 is thus retained regardless of the operating medium, and that is until the refrigerant is finally used up in the storage container 26.

Bei einer entsprechenden Wahl der Größe des Vorrats an Kältemittel 27 kann deshalb die Notkühlung ausreichend lange aufrechterhalten werden, um den eingetretenen Störfall beheben zu können.With an appropriate choice of the size of the supply of refrigerant 27, the emergency cooling can therefore be maintained for a sufficiently long time in order to be able to remedy the incident that has occurred.

Bei Eintritt eines Störfalles muß das Ventil 15 seine offene Stellung behalten, das Ventil 17 schließen und das Ventil 25 öffnen. Zweckmäßigerweise sind diese Ventile deshalb mit elektrischen oder elektropneumatischen Betätigungseinrichtungen ausgerüstet, die derart ausgebildet sind, daß die Ventile 15 und 25 bei Stromausfall ihre Offenstellung und das Ventil 17 bei Stromausfall seine Schließstellung einnehmen. Eine sichere Funktion der Notkühleinrichtung wird dadurch erreicht.When an accident occurs, the valve 15 must keep its open position, close the valve 17 and open the valve 25. Advantageously, these valves are therefore equipped with electrical or electropneumatic actuators which are designed such that the valves 15 and 25 assume their open position in the event of a power failure and the valve 17 in its closed position in the event of a power failure. This ensures a safe function of the emergency cooling device.

Bei der gestrichelt dargestellten Alternativlösung öffnet sich ebenfalls im Störfall das Ventil 25, während das Ventil 15 schließt. Das Kältemittel 27 strömt über die Leitung 24′ in die Kondensationsfläche 23′, verdampft dort und wird über die Leitung 32′ in die Atmosphäre abgeführt. Unmittelbar nach dem Eintritt des Störfalles wird die Kondensationsfläche 23′ ausreichend kalt, um das Vakuum in der Kammer 1 aufrechtzuerahalten. Die darin befindliche Produktcharge ist somit nicht gefährdet.In the alternative solution shown in dashed lines, valve 25 also opens in the event of a fault, while valve 15 closes. The refrigerant 27 flows via line 24 'into the condensation surface 23', evaporates there and is discharged via line 32 'into the atmosphere. Immediately after the occurrence of the accident, the condensation surface 23 'is sufficiently cold to maintain the vacuum in the chamber 1. The product batch contained therein is therefore not endangered.

Claims (7)

  1. Freeze-drying apparatus
    - having an evacuation chamber (1) containing shelves (2) for the product to be freeze-dryed,
    - having an evacuation system (11) that is connected to the chamber (1) via a pipe (14), this evacuation system being comprised of one condenser (12) with at least one condensation surface (18) and of a vacuum pump (13) connected to the condensor via a pipe (16),
    - having a refrigeration apparatus (5) which supplies the condensation surface (18) with a cooling agent, and
    - having an additional condensation surface (23, 23′) that is independent of the refrigeration apparatus (5), this condensation surface being connected through a valve (25) to a storage tank (26) of the low boiling point cooling agent (27) and this condensation surface being located either inside the condensor (12, condensation surface 23), inside the chamber (1, condensation surface 23′) or inside a separate chamber.
  2. Apparatus in accordance with claim 1 having an additional condensation surface (23′) inside the chamber (1) and with a valve (15) in the pipe (14) between the chamber (1) and the condensor (12).
  3. Apparatus in accordance with claim 2 wherein the valve (15) between the chamber (1) and the condenser (12) as well as the valve (25) between the additional condensation surface (23′) and the storage tank (26) are equipped with electrical or electro-pneumatic actuating devices in such a way that, upon loss of power, the valve (15) closes or remains in the closed position and the valve (25) opens or remains in the open position.
  4. Apparatus in accordance with claim 1 having an additional condensation surface (23) inside the condensor (12) and with a valve (15) and (17), respectively, between the chamber (1) and the condensor (12) and in the pipe (16) between the condensor (12) and the vacuum pump (13).
  5. Apparatus in accordance with claim 4 wherein the valve (15) between the chamber (1) and the condenser (12), the valve (17) between condensor (12) and vacuum pump (13) as well as the valve (25) between the additional condensation surface (23) and the storage tank (26) are equipped with electrical or electro-pneumatic actuating devices in such a way that, upon loss of power, the valve (17) closes or remains in the closed position and the valves (15) and (25) open or remain in the open position.
  6. Apparatus in accordance with any one of the previous claims wherein the storage tank (26) of the liquid cooling agent is equipped with devices (28, 29, 31) which serve to create an increased pressure inside the tank.
  7. Apparatus in accordance with any one of the previous claims wherein the cooling agent (27) in the storage tank (26) is liquid nitrogen.
EP87110955A 1987-07-29 1987-07-29 Freeze-drying apparatus Expired - Lifetime EP0301117B1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP87110955A EP0301117B1 (en) 1987-07-29 1987-07-29 Freeze-drying apparatus
ES87110955T ES2068809T3 (en) 1987-07-29 1987-07-29 DEVICE FOR LYOPHILIZATION.
DE3750847T DE3750847D1 (en) 1987-07-29 1987-07-29 Freeze-drying facility.
JP63173852A JP2676374B2 (en) 1987-07-29 1988-07-14 Freeze dryer
US07/226,536 US4949473A (en) 1987-07-29 1988-07-29 Freeze drying apparatus with additional condensation surface and refrigeration source

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP87110955A EP0301117B1 (en) 1987-07-29 1987-07-29 Freeze-drying apparatus

Publications (2)

Publication Number Publication Date
EP0301117A1 EP0301117A1 (en) 1989-02-01
EP0301117B1 true EP0301117B1 (en) 1994-12-07

Family

ID=8197162

Family Applications (1)

Application Number Title Priority Date Filing Date
EP87110955A Expired - Lifetime EP0301117B1 (en) 1987-07-29 1987-07-29 Freeze-drying apparatus

Country Status (5)

Country Link
US (1) US4949473A (en)
EP (1) EP0301117B1 (en)
JP (1) JP2676374B2 (en)
DE (1) DE3750847D1 (en)
ES (1) ES2068809T3 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108469151A (en) * 2018-02-10 2018-08-31 扬子江药业集团南京海陵药业有限公司 A kind of lyophilized technique that injection phosphoric acid l-ornidazole ester disodium is commercially produced

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2665338B1 (en) * 1990-08-02 1994-02-04 Blaizat Claude PROCESS OF CONCENTRATION, DEHYDRATION OF FOOD LIQUID OR OTHER, ITS DEVICE AND THE PRODUCT OBTAINED.
US5236041A (en) * 1991-07-22 1993-08-17 Hull Corporation Cyclonic vapor flow condenser
US5199187A (en) * 1991-07-31 1993-04-06 Sp Industries Freeze dryer apparatus having an interim condensing system and use thereof
DE4233479C2 (en) * 1991-10-04 1999-09-02 Inst Mikrobiologie Und Biochem Method and device for freeze drying, in particular liquids with microorganisms
JPH0735951B2 (en) * 1991-10-30 1995-04-19 西部瓦斯株式会社 Vacuum drying treatment device
US5291751A (en) * 1992-04-21 1994-03-08 Liquid Carbonic Corporation Cryo-mechanical vapor recovery apparatus
US5456084A (en) * 1993-11-01 1995-10-10 The Boc Group, Inc. Cryogenic heat exchange system and freeze dryer
US6122836A (en) * 1998-05-07 2000-09-26 S.P. Industries, Inc., The Virtis Division Freeze drying apparatus and method employing vapor flow monitoring and/or vacuum pressure control
US6220048B1 (en) * 1998-09-21 2001-04-24 Praxair Technology, Inc. Freeze drying with reduced cryogen consumption
EP1144930A1 (en) * 1999-01-05 2001-10-17 Universal Preservation Technologies, Inc. Vacuum control system for foam drying apparatus
WO2005073652A2 (en) * 2004-02-02 2005-08-11 I.M.T. Interface Multigrad Technology Ltd. Apparatus, system and method for lyophilization
CA2782908C (en) 2009-12-11 2016-02-09 Edward Weisselberg Apparatus and method for continuous lyophilization
WO2011078835A1 (en) * 2009-12-22 2011-06-30 Ima Life North America Inc. Monitoring freeze drying with gas measurement on vaccum pump exhaust
CN103123206A (en) * 2013-03-21 2013-05-29 楚天科技股份有限公司 Freeze dryer
WO2014190992A1 (en) 2013-05-29 2014-12-04 Gea Process Engineering A/S Method of providing inline sterile freeze drying of a product in trays accommodated in a trolley, system for carrying out the method, and use of the method
CN103344096A (en) * 2013-07-18 2013-10-09 上海千山远东制药机械有限公司 Freeze dryer water catcher
CN105509422B (en) * 2015-12-24 2018-09-25 甘肃银光化学工业集团有限公司 A kind of vacuum freeze-drying system and using the system to the method for energetic material vacuum freeze drying
CN106468501B (en) * 2016-08-29 2019-12-27 浙江金石生物科技有限公司 Nitrogen-protected dendrobium officinale freeze-drying device and freeze-drying method thereof
DE102016123490A1 (en) * 2016-12-05 2018-06-07 Innovations-Transfer Uphoff Gmbh & Co. Kg Process and device for drying in the steam explosion process
WO2020201822A2 (en) * 2019-01-27 2020-10-08 Nguyen Vien Lam Convection current freeze drying apparatus and method of operating the same
CN111504003B (en) * 2020-03-30 2021-06-11 广西农业职业技术学院 Freeze drying method and drying device thereof
CN113865273B (en) * 2021-09-01 2023-01-31 广州韩秀科技有限公司 Open negative pressure low-temperature drying equipment

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR784430A (en) * 1934-04-14 1935-07-22 Plant for the preparation of dry powder products
GB552821A (en) * 1941-12-18 1943-04-27 Arthur Sproul Mcfarlane Improvements in and relating to the desiccation of solutions at low temperatures
US2453033A (en) * 1945-03-08 1948-11-02 York Corp Vacuum drying apparatus using a refrigerant system for heating and cooling
US3230633A (en) * 1961-10-27 1966-01-25 Pennsalt Chemicals Corp Freeze drying apparatus and method
DE1196578B (en) * 1962-02-27 1965-07-08 Leybold Hochvakuum Anlagen Freeze-drying process with recovery of volatile components
DE1196579B (en) * 1962-02-27 1965-07-08 Leybold Hochvakuum Anlagen Method for controlling the drying temperature during freeze drying, depending on the partial pressure of a gas or steam present in the chamber
US3191395A (en) * 1963-07-31 1965-06-29 Chicago Bridge & Iron Co Apparatus for storing liquefied gas near atmospheric pressure
US3385073A (en) * 1966-10-06 1968-05-28 Cryo Therm Inc Refrigeration system for shipping perishable commodities
FR1586349A (en) * 1968-10-24 1970-02-13
US3648379A (en) * 1970-03-16 1972-03-14 Horton John T Continuous freeze drying system
US4060400A (en) * 1975-08-22 1977-11-29 Henry L. Franke Refrigerated semitrailer truck for long and local deliveries
US4353222A (en) * 1979-07-04 1982-10-12 Kyowa Vacuum Engineering, Ltd. Vacuum apparatus
JPS5728977A (en) * 1980-07-25 1982-02-16 Osaka Gas Co Ltd Vacuum refrigeration drying and apparatus used therefor
DE3107241A1 (en) * 1981-02-26 1982-09-09 Leybold-Heraeus GmbH, 5000 Köln Condenser for drying installations
JPS6015867A (en) * 1983-07-06 1985-01-26 Fujitsu Ltd Magnetic recording and reproducing device

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108469151A (en) * 2018-02-10 2018-08-31 扬子江药业集团南京海陵药业有限公司 A kind of lyophilized technique that injection phosphoric acid l-ornidazole ester disodium is commercially produced

Also Published As

Publication number Publication date
DE3750847D1 (en) 1995-01-19
ES2068809T3 (en) 1995-05-01
JP2676374B2 (en) 1997-11-12
EP0301117A1 (en) 1989-02-01
JPS6449882A (en) 1989-02-27
US4949473A (en) 1990-08-21

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