Pseudopolymorphic transformation

The phenomenon of pseudopolymorphism is also observed, i.e., compounds can crystallize with one or more molecules of solvent in the crystal lattice. Conversion from solvated to nonsolvated, or hydrate to anhydrous, and vice versa, can lead to changes in solid-state properties. For example, a moisture-mediated phase transformation of carbamazepine to the dihydrate has been reported to be responsible for whisker growth on the surface of tablets. The effect can be retarded by the inclusion of Polyoxamer 184 in the tablet formulation [61]. 

Everz, L. and Mielck, J. (1992). V feter-induced physical transformation of a crystalline drug in a uidized bed pseudopolymorphism-polymorphism of carbamazepiBa/ J. Pharm. Biopharm., 38 28S. 

Figure 9.19 (a) transformations between different polymorphs or pseudopolymorphs of 9.4, (b) TGA... 

Polymorphs and pseudopolymorphs can also be classified as monotropes or enantiotropes, depending upon whether or not one form can transform reversibly to another. In a monotropic system. Form I does transform to Form II, because the transition temperature cannot appear before the melting temperature (Fig. 5,... 

Figure 9.19 (a) transformations between different polymorphs or pseudopolymorphs of 9.4, (b) TGA thermograms of y8-[Ni(4-MePy)4(NCS)2] C6H6 (trace 1) and 7-[Ni(4-MePy)4(NCS)2]-2(C6H6) (trace 2) plotted as mass/n v.t. temperatnre (n is the nnmber of moles of each compound calculated from the mass of the final Ni(SCN)2 prodnct). Each experiment starts with crystals of an inclusion compound wetted with benzene (reprinted with permission from Section Key Reference 2004 American Chemical Society). 

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. 

A wide spectrum of analytical techniques may be used to characterize polymorphs and pseudopolymorphs in terms of their structure, spectral energies, thermodynamic stabilities, kinetics of transformation and solubility behaviour. 

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