Water, generally polymorphism

In general, polymorphs of a given compound have different physicochemical properties, such as melting point, solubility and density, so that the occurrence of polymorphism has important formulation, biopharmaceutical and chemical process implications. In addition to polymorphs, solvates (inclusion of the solvent of crystallization), hydrates (inclusion of water of crystallization) and amorphous forms (where no long-range order exists) may also exist. Figure 3.8 shows an example of the polymorphism of estrone (Busetta et al. 1973). 

It is not appropriate in this chapter to give a detailed review of the solid-state behaviour of water in its various crystalline modifications. However, there are some general structures which are relevant and worth highlighting. Firstly, water molecules in these various solids have dimensions and bond angles which do not differ much from those of an isolated water molecule. Secondly, the number of nearest neighbours to which each individual molecule is hydrogen-bonded remains four, regardless of the ice polymorph. 

The study of liquid crystals rapidly becomes complex because both the thermotropic and lyotropic types are polymorphic. The lyotropic type exists in at least six phases according to Brown Johnson. Materials of this type generally exhibit a molecular weight in the range of 250-500. Many of these materials are described as lipids, and frequently as phospholipids. On addition of water to a crystal composed of these materials, the molecular structure initially collapses to form a lamellar structure. Further dilution may result in additional structural changes before an isotropic solution is reached. 

The general term ice describes a wide range of solid phases formed by water (Franks, 1973 Kamb, 1968). Preparation of a pure polymorph is not straightforward. Ice-Ih is the most widely studied polymorph but considerable information is available concerning many others. Eight solid phases, Hi, II, III, V, VI, VII, VIII and IX, are shown in the phase diagram for ice (Franks, 1973). In addition, two more polymorphs, ice-lc and IV, are thermodynamically unstable. 

Because of kinetic factors, metastable forms are encountered in temperature ranges outside the thermodynamic range. Crystallization processes generally imply the cooling of concentrated solutions or precipitation by addition of cosolvent. Depending on the relative positions of the solubility curves of the metastable polymorphic forms and the metastable curve of supersaturation, the first nucleous can be a metastable form. Transformation to the stable crystalline form may or may not occur, depending on kinetic factor. Furthermore solvates exist at lower temperatures and their presence should be considered and finally due to the humidity of the air or from water activity of the solvents, hydrates may be formed. Polymorphism of solvates and hydrates is not uncommon. This phenomenon of concomittant polymorphs has been recently reviewed. ... 

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