Complex Ternary and Multicomponent Phase Behaviour

Consider a ternary aqueous mixture as cooling proceeds, three general types of phase behaviour can be distinguished, according to the properties of the residual solution after initial (primary) ice crystallisation  

A complete crystallisation of ice and all the solute(s) in real time is rare. Nevertheless, the physical and chemical properties of the freeze-dried product depend critically on the equilibrium phase behaviour, as defined by the phase rule, and also on any transient non-equilibrium excursions, induced by the particular processing conditions employed during freezing and drying. The system water-sucrose-NaCl serves as a good illustration of these three possibilities. 

Roman numerals represent crystalline hydrate phases I = S.3.5W II = S.2.5W III = NaCl.2- 

Crystal habit Prismatic rods Prismatic rods 

Similar results were obtained by substituting KCl for NaCl, but LiCl produced a lower eutectic point and also inhibited the crystallisation of mannitol. The earlier paragraphs may suggest to the product developer that, even if only for regulatory reasons, the use of mannitol in pharmaceutical preparations should be avoided, a valid conclusion in the author s own experience. 

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