Solvatomorphism, types

Several of the chapters in the current volume are comprehensive in nature, but others are more specialized. Volume 32 also contains a methodology review article on the validation of chromatographic methods of analysis. New to the series are annual reviews, and volume 32 contains a summary of the publications appearing during 2004 that dealt with polymorphism and solvatomorphism. It is anticipated that future volumes in the Profiles series will contain similar methodology reviews, as well as other types of review articles that summarize the current state in a particular field of pharmaceutics. As always, I welcome communications from anyone in the pharmaceutical community who might want to provide an opinion or a contribution. 

The phase transformation relationships for the solvatomorphs of naproxen sodium have been reported [71], The dihydrate phase is obtained upon crystallization from water, and a monohydrate phase could be prepared by the dehydration of the dihydrate phase in a desiccator (RH = 0%) for two days. The anhydrate phase could be obtained from either the monohydrate or dihydrate by drying the substance in an oven at 120 °C for two hours. Thermal analysis data was used to demonstrate the existence of two types of water in the dihydrate phase, and that each could be removed at a characteristic temperature. 

One may define a solvatomorph as a crystalline solid in which solvent molecules have become included in the structure through the existence of positional substitution at positions that are site specific and that are related to other solvent molecules through translational symmetry. Other types of structural solvation exist but will not be discussed here. Since water is such a ubiquitous substance, it is not surprising that the most important type of solvatomorphism involves the incorporation of water into a crystal lattice. 

Studies of the desolvation of solvatomorphs can be conducted using VT-XRPD. For instance, after the dehydration of a hydrate phase, one may obtain either a crystalline anhydrate phase or an amorphous phase and the XRPD pattern will clearly indicate the difference. In addition, should one encounter an equivalence in powder patterns between the hydrate phase and its dehydrated form, this would indicate the existence of channel-type water (as opposed to lattice boimd water). In one study, the solid-state properties of the isomorphic desolvates of cephalexin, cefaclor, erythromycin A, and spirapril hydrochloride were investigated, with the hygroscopicity of the compounds being evaluated using a vacuum moisture balance and the structural relaxation measured using a combination of VT-XRPD and isothermal microcalorimetry. " ... 

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