WO2018036861A1 - Procédé et dispositif de lyophilisation - Google Patents

Procédé et dispositif de lyophilisation Download PDF

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Publication number
WO2018036861A1
WO2018036861A1 PCT/EP2017/070644 EP2017070644W WO2018036861A1 WO 2018036861 A1 WO2018036861 A1 WO 2018036861A1 EP 2017070644 W EP2017070644 W EP 2017070644W WO 2018036861 A1 WO2018036861 A1 WO 2018036861A1
Authority
WO
WIPO (PCT)
Prior art keywords
pressure
product
condenser
product chamber
valve
Prior art date
Application number
PCT/EP2017/070644
Other languages
German (de)
English (en)
Inventor
Timo HEINZ
Jens Philipp
Original Assignee
OPTIMA pharma GmbH
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by OPTIMA pharma GmbH filed Critical OPTIMA pharma GmbH
Priority to ES17752124T priority Critical patent/ES2883334T3/es
Priority to SI201730848T priority patent/SI3504496T1/sl
Priority to DK17752124.2T priority patent/DK3504496T3/da
Priority to PL17752124T priority patent/PL3504496T3/pl
Priority to EP17752124.2A priority patent/EP3504496B1/fr
Publication of WO2018036861A1 publication Critical patent/WO2018036861A1/fr

Links

Classifications

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

Definitions

  • the invention relates to a method and a device for freeze-drying.
  • Freeze-drying also referred to as lyophilization or sublimation drying, is a process for the gentle drying of high-quality products, in particular pharmaceutical products or biotech products, for example vaccines, or foods, in particular for the production of milk powder.
  • the product refers to any preparation which is suitable for freeze-drying.
  • preparations which are suitable for freeze-drying.
  • liquid or semisolid aqueous preparations such as, for example, solutions, emulsions or suspensions.
  • the products to be dried are filled in containers, such as small vials, so-called vials, injection bottles or other and dried in these.
  • Known freeze-drying plants comprise a product chamber in which a condenser is arranged or which is connected to a condenser.
  • a plurality of superimposed, heatable and coolable control plates are provided, on which the containers, in particular the vials, are placed with the product to be dried filled in,
  • Cooling and freezing of the product takes place prior to the actual drying operation, usually cooling the product to a certain freezing temperature and maintaining the freezing temperature until the solvent content of the product has been frozen. Freezing is usually carried out at atmospheric pressure. Freezing is also called crystallization. The beginning of freezing is called nucleation or nucleation.
  • the drying process following freezing can be divided into primary drying and secondary drying.
  • primary drying a vacuum is applied and the solvent contained in the product at temperatures below freezing sublimated.
  • secondary drying more solvent bound in the product is evaporated.
  • a vacuum-induced freezing is known, wherein first at a temperature in the product chamber which is above the freezing point of the product, a pressure in the product chamber is lowered until onset of visible crystallization of the solvent.
  • the temperature of the control panels is for example at +10 ° C.
  • the temperature in the drying chamber is lowered to a temperature below or equal to the freezing point of the product until crystallization of the solvent is complete.
  • a primary drying is carried out by sublimation of the solvent under reduced pressure.
  • nucleation or nucleation begins in a varying pressure range depending on the type and concentration.
  • the time between nucleations may be several minutes. This can result in sublimation of the first frozen products, which manifests itself in small, dry areas on the surface.
  • a process for freeze-drying products in a product chamber connected to a condenser via a valve comprising the steps of: a) lowering the pressure in the product chamber and the condenser at a temperature below the freezing point of the product, until a defined pressure is reached which is below the atmospheric pressure and above a product-specific nucleation pressure at which nucleation begins; b) closing the valve between the product chamber and the condenser; c) maintaining the pressure in the product chamber and further lowering the pressure in the condenser; and d) opening the valve between the product chamber and the condenser after or upon reaching the product specific nucleation pressure in the condenser so that the pressure in the product chamber is lowered to a pressure below the product specific nucleation pressure.
  • the steps cause a vacuum-induced nucleation.
  • a pressure drop in the product chamber is achieved with a high pressure drop rate, with a pressure below the product-specific nucleation pressure being established in the product chamber.
  • a pressure range within which the products freeze in conventional vacuum-induced nucleation processes is almost skipped. As a result, all products nucleate in a small amount of time. Since a pressure in the product chamber has already been lowered before the pressure drop, only a pressure difference of a few millibars can be compensated.
  • a cooling of the product chamber is preferably carried out by means of known control panels.
  • the control plates arranged in the product chamber are cooled to a temperature of about -20 ° C. to about -3 ° C., in particular from about -14 ° C. to about -5 ° C.
  • the temperature of the control panels is kept constant in advantageous embodiments via the steps a) to d) of the process.
  • the product-specific nucleation pressure and / or the pressure range to be skipped by closing and opening the valve are, depending on the application, by the person skilled in the art, For example, depending on the product and / or a size of the product chamber suitable selectable.
  • the pressure in the condenser is lowered to a pressure in the range of about 0.005 to about 3 mbar.
  • the pressure in the product chamber is lowered by opening the valve by about 0.3 mbar to about 2.5 mbar and / or the pressure in the product chamber by opening the valve to a pressure is lowered below the triple point of the product.
  • the vacuum-induced nucleation takes place in the case of the invention at a temperature which is below the freezing point of the product.
  • the pressure drop causes not only a nucleation, but a complete crystallization of the products.
  • a step is provided for freezing the products, for which purpose the product chamber is further cooled.
  • the low pressure level is maintained in the product chamber.
  • subsequent freezing and sublimation of the solvent occurs while maintaining the pressure established between the product chamber and the condenser after opening the valve.
  • the pressure in the product chamber is increased for complete freezing, for example, the product chamber is returned to atmospheric pressure .
  • the temperature of the control panels also remains unchanged for freezing and sublimation in one embodiment.
  • apparatus for freeze-drying products comprising a product chamber, a condenser connected to the product chamber via a valve, and a controller, the controller being arranged and configured to perform the method described above.
  • the control device is designed in one embodiment such that a completely automatic implementation with predefinable process parameters is possible.
  • the control device comprises, for example, adjusting elements for actuating the valve provided between the product chamber and the condenser.
  • a semi-automatic implementation is carried out.
  • the control device transmits, for example, acoustic or optical signals, by means of which a user is assisted in carrying out the method. For example, a user is asked to close or open the valve between the product chamber and the condenser.
  • Fig. 1 is a schematic representation of a device according to the invention for
  • FIG. 2 shows a schematic illustration of the apparatus for freeze drying according to FIG. 1 with the valve closed;
  • Fig. 3 is a schematic representation of the apparatus for freeze drying of Figure 1 at a pressure equalization with the valve open.
  • FIG. 4 schematically shows a profile of a product temperature and a profile of the pressure in a product chamber when carrying out the method according to the invention.
  • a device 1 for freeze-drying products comprising a product chamber 2 with control plates 20, a condenser 3 connected to the product chamber 2 via a valve 4, and a control device 5.
  • the device 1 further comprises a vacuum pump 6 connected to the condenser 3 is connected via a valve 60.
  • FIGS. 2 and 3 show the apparatus 1 for freeze drying according to FIG. 1 with the valve 4 closed or open, wherein the control device 5 is not shown in FIGS. 2 and 3 for a better overview.
  • a central control device 5 which with the control plates 20, the condenser 3, the valve 4, the valve 60 and the vacuum pump 6 or elements thereof for the exchange of sensor and / or control signals wireless or connected via data lines.
  • the communication paths represented by arrows are only to be understood schematically and show no wiring.
  • a plurality of control devices are provided. Further, each or each of said components may have its own control device be assigned, by means of which, for example, a temperature control of the control plates 20 is carried out to a predetermined by the central control device 5 temperature.
  • valve 4 is opened and the product chamber 2 is communicated with the condenser 3.
  • a temperature in the product chamber 2 and the condenser is lowered to a value which is below the freezing point of the product. This is done in advantageous embodiments by the control plates 20 are cooled to a lying at about 3 to 20 ° C below the freezing point of the product temperature.
  • the pressure in the product chamber 2 and the condenser 3 is first lowered until a first defined pressure is reached, which lies below the atmospheric pressure and above a product-specific nucleation pressure at which nucleation begins.
  • the vacuum pump 6 is operated appropriately, wherein an operation of the vacuum pump 6 is effected for example by means of the control device 5.
  • the first defined pressure can be specified product-specifically by a person skilled in the art, for which purpose the control device 5 in one embodiment has a human-machine interface.
  • the valve 4 Upon reaching the first defined pressure, the valve 4 is closed.
  • a pressure in the product chamber 2 and the condenser 3 is monitored by means of the control device 5 and effected by means of the control device 5, an actuation of the valve 4 upon reaching the first defined pressure.
  • the valve 4 is actuated by a user.
  • the valve 4 When the second defined pressure is reached, the valve 4 is opened.
  • a pressure in the condenser 3 is also monitored by means of the control device 5 and by means of the control device 5 an actuation of the valve 4 upon reaching the second defined pressure causes.
  • the valve 4 is actuated by a user.
  • the second defined pressure can also be specified product-specifically by a person skilled in the art. In other embodiments, it is provided that the pressure is set by the person skilled in the art, which should set in the product chamber 2 after opening the valve 4, wherein the control device 5 based on this value taking into account the properties of the device 1, such as the size of the product chamber 2, the second defined pressure determined. In still other embodiments, the pressure in the condenser 3 is lowered over a predetermined period of time.
  • Fig. 3 shows the device 1 after opening the valve 4 between the product chamber 2 and the condenser 2 after or when reaching the second defined pressure in the condenser 3, wherein as indicated by arrows in Fig. 3, the pressure in the product chamber 2 on a pressure below the product-specific nucleation pressure is lowered.
  • FIG. 4 schematically shows a profile of a product temperature 7 and a profile of the pressure 8 in a product chamber 2 (see FIG. 1) when carrying out the method according to the invention.
  • the temperature of the adjusting plates 20 in the product chamber 2 (see Fig. 1 to 3) is represented by a line 9.
  • the temperature of the control plates 20 is about -10 ° C.
  • a pressure 8 in the product chamber 2 and the condenser 3 (see Fig. 1) is lowered until a first defined pressure is reached, which is below the atmospheric pressure and above a product-specific nucleation pressure at which nucleation begins , lies.
  • a second step b the valve 4 between the product chamber 2 and the condenser 3 is closed.
  • a third step c the pressure in the product chamber is maintained and the pressure in the condenser 3 is lowered further until a second defined pressure is reached which is below the product-specific nucleation pressure.
  • a fourth step d) the valve 4 is opened between the product chamber 2 and the condenser 3, thereby achieving pressure equalization.
  • the pressure compensation causes the pressure in the product chamber 2 to be lowered in a short time to a pressure below the product-specific nucleation pressure.
  • the pressure which has been lowered to approximately OJmbar, causes a nucleation, the nucleation taking place in all products within a product chamber 2 almost simultaneously. Due to the prevailing low temperature, the products freeze completely with small filling quantities, without a further lowering of the temperature of the adjusting plates 20 is necessary.
  • the period of time at which the products are completely frozen or crystallized is indicated by II.
  • Subsequent sublimation of the frozen product takes place in the illustrated embodiment likewise while maintaining the pressure which is established after conclusion of step 4) and while maintaining the temperature of the control plates at about -10 ° C.
  • these process parameters are merely exemplary and the inventive steps for improved freezing operation can be combined with other process steps for complete freezing or drying.

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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)
  • Confectionery (AREA)

Abstract

L'invention concerne un procédé de lyophilisation de produits dans une chambre de produit (2), la chambre de produit (2) étant reliée à un condenseur (3) par le biais d'une soupape (4), le procédé comportant les étapes consistant à : ∙ a) abaisser la pression dans la chambre de produit (2) et le condenseur (3) à une température qui est inférieure au point de congélation du produit, jusqu'à ce qu'une pression définie soit atteinte, laquelle est inférieure à la pression atmosphérique et supérieure à une pression de nucléation spécifique au produit à laquelle une nucléation commence ; ∙ b) fermer la soupape (4) entre la chambre de produit (2) et le condenseur (3) ; ∙ c) maintenir la pression dans la chambre de produit (2) et abaisser davantage la pression dans le condenseur (3) ; ∙ d) ouvrir la soupape (4) entre la chambre de produit (2) et le condenseur (3) après que la pression de nucléation spécifique au produit a été atteinte ou lorsqu'elle est atteinte dans le condenseur (3), de sorte que la pression dans la chambre de produit (2) soit abaissée à une pression inférieure à la pression de nucléation spécifique au produit. L'invention concerne en outre un dispositif permettant de mettre en œuvre le procédé.
PCT/EP2017/070644 2016-08-23 2017-08-15 Procédé et dispositif de lyophilisation WO2018036861A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
ES17752124T ES2883334T3 (es) 2016-08-23 2017-08-15 Método y dispositivo para deshidrocongelar
SI201730848T SI3504496T1 (sl) 2016-08-23 2017-08-15 Postopek in naprava za liofilizacijo
DK17752124.2T DK3504496T3 (da) 2016-08-23 2017-08-15 Fremgangsmåde og apparat til frysetørring
PL17752124T PL3504496T3 (pl) 2016-08-23 2017-08-15 Sposób i urządzenie do suszenia przez wymrażanie
EP17752124.2A EP3504496B1 (fr) 2016-08-23 2017-08-15 Méthode et dispositif pour lyophiliser

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102016215844.9 2016-08-23
DE102016215844.9A DE102016215844B4 (de) 2016-08-23 2016-08-23 Verfahren und Vorrichtung zur Gefriertrocknung

Publications (1)

Publication Number Publication Date
WO2018036861A1 true WO2018036861A1 (fr) 2018-03-01

Family

ID=59626621

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2017/070644 WO2018036861A1 (fr) 2016-08-23 2017-08-15 Procédé et dispositif de lyophilisation

Country Status (7)

Country Link
EP (1) EP3504496B1 (fr)
DE (1) DE102016215844B4 (fr)
DK (1) DK3504496T3 (fr)
ES (1) ES2883334T3 (fr)
PL (1) PL3504496T3 (fr)
SI (1) SI3504496T1 (fr)
WO (1) WO2018036861A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102017217415B4 (de) 2017-09-29 2022-11-10 OPTIMA pharma GmbH Verfahren und Vorrichtung zur Gefriertrocknung

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000040910A1 (fr) * 1999-01-05 2000-07-13 Universal Preservation Technologies, Inc. Systeme de commande de vide pour appareil de sechage de mousse
DE19936281A1 (de) 1999-08-02 2001-02-15 Bayer Ag Neues Verfahren zur Gefriertrocknung
US20030116027A1 (en) * 2000-04-19 2003-06-26 Brulls Mikael Johan Alvin Method of monitoring a freeze drying process
US20100107436A1 (en) * 2006-09-19 2010-05-06 Telstar Technologies, S.L. Method and system for controlling a freeze drying process
US20100242301A1 (en) * 2007-02-05 2010-09-30 Bryce Mark Rampersad Freeze-dryer and method of controlling the same
US20120102982A1 (en) * 2006-02-10 2012-05-03 Ying Zhou Method and system for nucleation control in a controlled rate freezer (crf)
CN104677084A (zh) * 2015-02-13 2015-06-03 黄少峰 一种瞬时降压装置及具有该装置的冻干设备

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19654134C2 (de) 1996-04-25 2003-08-07 Messer Griesheim Gmbh Verfahren und Einrichtung zum Gefriertrocknen
DE19719398A1 (de) 1997-05-07 1998-11-12 Amsco Finn Aqua Gmbh Verfahren zur Steuerung eines Gefriertrocknungsprozesses
DE20008915U1 (de) 2000-05-19 2001-06-28 Martin Christ Gefriertrocknungsanlagen GmbH, 37520 Osterode Gefriertrocknungsanlage
DE102004007526A1 (de) 2004-02-17 2005-09-01 Oetjen, Georg-Wilhelm, Dr. Verfahren und Einrichtung zur Gefriertrocknung von Produkten
US8839528B2 (en) 2011-04-29 2014-09-23 Millrock Technology, Inc. Controlled nucleation during freezing step of freeze drying cycle using pressure differential ice fog distribution

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000040910A1 (fr) * 1999-01-05 2000-07-13 Universal Preservation Technologies, Inc. Systeme de commande de vide pour appareil de sechage de mousse
DE19936281A1 (de) 1999-08-02 2001-02-15 Bayer Ag Neues Verfahren zur Gefriertrocknung
US20030116027A1 (en) * 2000-04-19 2003-06-26 Brulls Mikael Johan Alvin Method of monitoring a freeze drying process
US20120102982A1 (en) * 2006-02-10 2012-05-03 Ying Zhou Method and system for nucleation control in a controlled rate freezer (crf)
US20100107436A1 (en) * 2006-09-19 2010-05-06 Telstar Technologies, S.L. Method and system for controlling a freeze drying process
US20100242301A1 (en) * 2007-02-05 2010-09-30 Bryce Mark Rampersad Freeze-dryer and method of controlling the same
US8240065B2 (en) 2007-02-05 2012-08-14 Praxair Technology, Inc. Freeze-dryer and method of controlling the same
CN104677084A (zh) * 2015-02-13 2015-06-03 黄少峰 一种瞬时降压装置及具有该装置的冻干设备

Also Published As

Publication number Publication date
DK3504496T3 (da) 2021-07-05
DE102016215844A1 (de) 2018-03-01
DE102016215844B4 (de) 2018-03-29
SI3504496T1 (sl) 2021-08-31
EP3504496B1 (fr) 2021-04-28
EP3504496A1 (fr) 2019-07-03
PL3504496T3 (pl) 2021-11-02
ES2883334T3 (es) 2021-12-07

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