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Dr. Henning Gieseler - Articles and news items
Issue 5 2012, Lyophilisation / 22 October 2012 / Henning Gieseler, Associate Professor at the Division of Pharmaceutics, University of Erlangen & CEO, GILYOS GmbH and Peter Stärtzel, Pharmaceutical Scientist, GILYOS GmbH
The stochastic nature of nucleation during the freezing step of the freeze-drying process has been regarded as a demerit in a process which is considered under rigorous control. The freezing performance of a product can impact its subsequent drying behaviour and the final product quality attributes. Hence, the idea to control this stochastic event and thus to directly influence the product morphology seems highly appealing. Sound understanding of the nature of nucleation and its link to drying performance, as well as the choice of a suitable technical concept, is of fundamental importance and the prerequisite to profit from the opportunities offered by controlled nucleation.
Freeze-drying is a commonly used method within the pharmaceutical industry. One of the key steps of the entire process is the initial freezing procedure. During freezing of an aqueous solution, the formation of ice does not start at the equilibrium freezing temperature, Tf (Figure 1, page 64). Instead, the solution shows supercooling below Tf until the first ice nuclei are formed at the nucleation temperature, Tn. Nucleation itself proceeds in a three-phase process. ‘Primary nucleation’ describes the point where initial crystal nuclei appear from molecular clusters exceeding a critical size1,2. The formed nuclei are further grown to ice crystals by secondary nucleation (also referred to as ‘crystallisation’) passing through the already nucleated volume1.
Pharmaceutical freeze-drying is used to stabilise delicate drugs which are typically unstable in solution over a longer shelf life. The liquid formulation is converted into a solid, highly porous cake which can be easily reconstituted prior to administration. The majority of freeze-dried products in the pharmaceutical industry are used for parenteral application. This route of administration demands high quality for both the drug product and the primary packaging material. Today, glass vials are routinely used for freeze-dried products as they provide some indispensable characteristics. Depending on glass composition, surface treatment, processing and geometry, a vast number of different glass vials are commercially available for customers. Selection of the optimum vial for a given product seems to become more and more difficult as manufacturers of moulded and tubing glass have refined their products over the last decades to fulfil market needs.
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