Non-stoichiometric hydrates

Moisture desorption isotherm of a non-stoichiometri hydrate. All measured points are in equilibrium.

In comparison to the restricted stoichiometric hydrates, non-stoichiometric hydrates can vary in water content without major change in their crystal structure. The amount of water in the crystal lattice only depends on the partial pressure of water in the surrounding atmosphere. In the fully hydrated state, non-stoichiometric hydrates may, but not necessarily have to, show an integer ratio of water to host molecules. Thus a non-stoichiometric monohydrate generally has a water content of one molecule of water per host molecule when fully occupied, but may have significantly less while maintaining the same structure. During drying of these hydrates, a considerable proportion of water can often be removed without significantly disturbing the crystal network, and in fact the crystals can subsequently rehydrate to give the initial crystal form. Unlike stoichiometric hydrates, the dehydration and rehydration of non-stoichiometric hydrates is not accompanied by a phase transition, and thus all hydration states represent the same crystal form.

Structurally, non-stoichiometric hydrates show normally channels or networks, through which the water molecules can diffuse. It is also common that the solvent in these channels adopts a disordered state, as it does not interact with the host network strongly, e.g. through hydrogen bonds. Depending on the size of these channels, they can also be occupied by other solvent molecules, which can be present as only species or in combination with water. This has been shown in the case of the broad-spectrum cephalosporin antibiotic cefamandole sodium,1 which can be crystallised as a methanol solvate exhibiting non-stoichiometric characteristics. Storing this crystal form in the presence of water vapour yields the hydrate, which also exhibits non-stoichiometric characteristics. In the case of finasterid, several channel solvates with isolated sites of water molecules have been described.2 At higher relative humidities during the moisture sorption experiments, it was observed that the channel solvate exchanges with atmospheric water, which destabilises the crystal network. Subsequent lowering of the humidity results then in the collapse of the crystal form and the formation of a new non-solvated crystal phase.


1 M. J. Pikal, J. E. Lang and S. Shah, Int. J. Pharm., 1983, 17, 237-262.

2 S. Byard, A. Abraham, P. J. T. Boulton, R. K. Harris and P. Hodgkinson, J. Pharm. Sci., 2012, 101, 176-186.