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    HOF SynchroFreeze – for optimized freeze drying processes

    products-servicesHOF Sonderanlagenbau GmbH
    July 24th 2020

    HOF has developed SynchroFreeze as a solution for controlled nucleation, which is increasingly used in advanced pharmaceutical freeze-drying processes to optimize product structure and significantly reduce drying times.

    The HOF SynchroFreeze option provides the user with an innovative tool to increase the quality of the pharmaceutical product and simultaneously ensures an efficient operation of the freeze drying systems.

    Product-specific test results confirm the high expectations for the SynchroFreeze technology, which requires only limited modifications for implementation into an existing system.

    SynchroFreeze Conditioning and Freezing

    SynchroFreeze is characterized by a conditioning phase, followed by cooling and vacuum-induced nucleation during the freezing process.

    • In the conditioning phase, dissolved gases are withdrawn from the liquid product under partial vacuum, in order to prevent strong gas bubble formation and bulging of the product in the subsequent freezing steps.
    • In the second phase, the now largely degassed liquid is cooled and the nucleation is triggered at the desired freezing point by a further pressure drop in the lower millibar range.

    Conditioning times vary, depending on the product, liquid level and temperature.

    In many application cases, a required supercooling can be achieved by setting shelf temperature while reducing the pressure level in the freeze-drying chamber. After completion of these steps, the product is liquid and put at the required supercooling level.

    The pressure reduction enables a rapid temperature change at the product surface, ensuring and very efficient evaporation of the solvent contents on the liquid surface with local cooling and triggering a freezing and crystallization process that progresses from the surface downward.

    Rapid pressure reduction also enables homogeneous freezing of content in vials.

    SynchroFreeze benefits

    In summary, HOF SynchroFreeze offers the following clear benefits:

    • optimized freeze drying processes
    • synchronized freezing for individual vials or product containers
    • Conditioned product structure
    • Improved product homogeneity
    • Reduced required drying times
    • More efficient lyophilization with reduced energy consumption

    Studies on SynchroFreeze have been carried out by different HOF development teams that have produced publications describing application-related adjustments of the freezing phase.

    In many cases, the targeted application of SynchroFreeze allows the optimization of the product structure as well as a significant reduction of drying times.

    Further studies are now examining  the positive influence of SynchroFreeze on reconstitution times for lyophilizates, where the enlarged structure of the frozen lyophilizate simplifies the entry of the solvents and has a favorable effect for the reconstitution process.

    Moreover, the selection of the freezing point and the subsequent pressure adjustments offer further optimization potential even for difficult products.

    HOF Business Development Manager Gerhard Schilder comments: “Implementation of HOF SynchroFreeze has potential to improve the performance of all freeze drying systems, especially in terms of their energy efficiency. It will be now exciting to observe the industrial use of the future-oriented process technology. We enjoy meeting these new challenges and tasks.”


    Click on HOF Corporate Video for more on controlled nucleation.


    Freeze Drying Systems by HOF

    HOF SynchroFreeze – for optimized freeze drying processes

    Scanning electron micrograph, product structure after application of SynchroFreeze during freezing and following freeze-drying (courtesy IDT Biologika)

    HOF SynchroFreeze – for optimized freeze drying processes

    Crystal growth after vacuum-induced nucleation

    HOF SynchroFreeze – for optimized freeze drying processes

    The controlled nucleation process showing relationships between temperature and pressure. From Allmendinger, A., et al. (2016)

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