Pseudopolymorphism phase transitions

McCrone (1965) also noted that second-order phase transitions have been termed as pseudopolymorphic. Such transitions are difficult to detect by optical methods, because of the small structural changes that occur hence, the origin of the prefix pseudo sometimes used to describe them. However, the birefringence of the crystals changes during such phase changes (see Section 4.2), so the use of crossed polarizers makes the phase change readily detectable. 

Accelerated stability studies are potentially problematic for at least three reasons. Stress testing conditions may exceed the temperature of a polymorphic phase transition or dehydration. The use of accelerated conditions may make a relaxation of a metastable phase more rapid due to the increased molecular mobility. Finally, the relative humidity of the station may be in the range sufficient to cause a pseudopolymorphic transition due to dehydration or hydration. It is sobering... 

This type of behaviour is not confined to polymorphs but may extend to pseudopolymorphic forms such as hydrates and solvates. A recent case of solvent-mediated phase transformation involved polymorphic and pseudopolymorphic forms of thiazole carboxylic acid [55], where the transformation is again sensitive to the composition of the mixed solvent. Three forms of the compound are known, an anhydrous form, a 0.5 hydrate, and a 1.5 hydrate. In 50-80% solutions (% = vol.% MeOH-H20), transformation of the 1.5 hydrate to the 0.5 hydrate was observed while transformation to the anhydrous form occurred in 85-100% solutions. No transformation occurred in 0-30% solutions. Detailed study of a solvent-mediated polymorphic transition has also been carried out for the antiulcerative agent cimetidine [56] for which seven polymorphic forms are known. An important feature of this study was the systematic use of seed crystals to induce crystallization at different supersaturation ratios. 

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