Hydrates carbamazepine dihydrate

Hydrates can sometimes be obtained by simply suspending the anhydrous material in water, whereupon a form of Ostwald ripening occurs. For instance, aqueous suspensions of anhydrous metronidazole benzoate are metastable, and storage at temperatures lower then 38°C leads to monohydrate formation accompanied by crystal growth [65]. Sorbitol provides another example of this behavior, where slow cooling of a saturated aqueous solution yields long thin needles of sorbitol hydrate [66]. When suspended in water, anhydrous carbamazepine is transformed to carbamazepine dihydrate [67]. In other instances, hydrates can be obtained from mixed solvent systems. 

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]. 

Aqueous granulation in a high shear mixer or a Luid bed can cause hydrate formation, and the subsequent drying can cause desolvation. Carbamazepine was transformed from one anhydral (form III) to another (form I) through a dihydrate intermediate when both of these processes were used (Everz and Mielck, 1992). The heat of drying can also cause the conversion of one form to another, as seen with chloramphenicol palmitate by DeVilliers et al. (1991). 

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