Eutectic Crystallisation of pH Buffer Components

Eutectic formation, as predicted by the phase rule, can have a dramatic effect on pH buffer solutions during freezing. In a ternary solution of two salts and water, four eutectic points may, in principle, be identified, of which one is a ternary eutectic (at the lowest temperature), while the other three are binary eutectics of the three pairs of components. Some eutectic data for sodium and potassium phosphate buffer salts with ice are summarised in Table For mixtures of the sodium salts, the 

Data from Van den Berg and Rose and Murase and Franks.  

An example of a previously unknown hydrate was recently reported for mannitol, a commonly used excipient in pharmaceutical freeze-drying. It was formed inadvertently during the particular drying protocol used. It was identified as a hydrate by X-ray diffraction, differential scanning calorimetry (DSC) and thermogravimetry, and it will be further discussed in a later chapter. 

The actual crystallisation behaviour of any given solute during freezing depends on its nucleation rate, which, in turn, is affected by the following factors  

2H20 is of a fairly simple nature and that the ionic interactions favouring nucleation and crystal growth are strong compared to ionic hydration interactions. 

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