Freeze-Drying ? an Art or a Science?
Although techniques for the study of Tg? are well established, there has been little commercially available equipment for the study of Tc itself until the launch of the BTL ?Lyostat? freeze-drying microscope a few years ago. The latest version, 'Lyostat 2' (see Figure 2), is a fully integrated freeze-drying microscope that enables collapse or eutectic melting temperatures to be observed in situ. Additional changes in the material may also be analysed using microscopy techniques such as polarised light analysis and differential interference contrast (DIC). Freeze-drying microscopy provides valuable information that can be fed back into both formulation and cycle development processes. Used in combination, instruments such as Lyostat and Lyotherm can provide a comprehensive means of formulation characterisation in terms of freeze-drying behaviour and critical temperatures.
From the sublime?
Additional (further) drying typically consists of the desorption of unfrozen water from the bulk dried product. This requires more energy than sublimation, since any physico-chemical interaction of the water with the bulk dried material needs to be broken before the water can be removed. This part of the process is governed by adsorption-desorption isotherms, and tends to be favoured by the use of higher temperature and lower pressure conditions than those typically employed in the main drying step. However, care often needs to be taken with heat-sensitive materials such as biologically active proteins, which may undergo damage (for example, denaturation or aggregation) if inappropriate conditions are employed even towards the end of secondary drying.
The final product
Generally, one looks for the final freeze-dried product to fulfil a number of set criteria, which for biotechnology products and pharmaceuticals might typically include maintenance of cosmetic acceptability, good reconstitution characteristics, appropriate moisture content and good shelf-life. Due to the complex interrelationship between the numerous product and process variables, some developmental work may be required to achieve these criteria. However, the advent of new technologies is enabling such work to be approached on a more rational basis.
The science of freeze-drying
The more we learn about freeze-drying, the more it reveals itself to be an exact (yet complex) science, rather than the ?art? (or even scientific curiosity) it was historically thought to be. However, there is clearly much more to be done in order for the process to be understood more fully and Biopharma Technology Limited strives to build upon its current position at the forefront of freeze-drying technology to rationalise the process further using a scientific approach.
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