Lyophilisation or freeze drying is widely used during the production of pharmaceutical and biological products to increase their stability. Developed during the 1940s, lyophilisation produces a dry product (cake) that can be readily reconstituted to its original form by adding water. It prolongs product shelf-life by impeding the chemical, microbiological and physical degradation pathways that arise in the presence of moisture, particularly when long periods of storage and/or transit prior to use are involved.
The lyophilisation process comprises three main stages: freezing (solidification), primary drying (ice sublimation) and secondary drying (moisture desorption). The specific process conditions applied during the freezing step will determine the structure of the resulting product cake. The size of the ice crystals will determine the sublimation speed during primary drying. The larger the ice crystals, the faster the primary drying process will be, owing to reduced mass flow resistance. The nucleation of ice crystals (the initial stage of ice formation during freezing) is, however, a naturally spontaneous and protracted process. As such, forcing ice crystals to nucleate at a specific temperature, rate and time can improve the homogeneity of the batch and reduce the cycle duration. The temperature profile after ice nucleation is critical for subsequent ice crystal growth.
Spontaneous and uncontrolled nucleation is random and time-consuming. Ice-nucleation temperatures in individual vials can vary from –10 to –20 °C, resulting in nucleation durations of up to an hour for the entire batch and differing crystal structures. It was important, therefore, to develop a method to induce nucleation — particularly for industrial-scale freeze dryers — to overcome this problem.
LYOSPARK, a patent pending technology from GEA, ensures inter-batch homogeneity, improves process repeatability and enhances both the appearance and quality of the final product. A new GMP-compliant SCADA recipe has been designed to perform controlled nucleation without the need for human intervention. In addition, a validation protocol has been implemented to ensure the correct functionality of the application.
It is important to highlight that cycle time reduction is not constant; it is highly dependent on the specifics of the product being freeze dried. However, time reductions of up to 30% have been achieved during the development and testing of the new technology.
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