Characterization of a Polymorphic System Exhibiting Substantial Variation of Solubility in a Fluorinated Solvent

We report several aspects of the characterization of a material (triacetylated-β-cyclodextrin) that exists in two crystalline polymorphic forms (denoted I and II). A striking feature of this polymorphic system is that polymorph I (MPt 194 °C) and polymorph II (MPt 219 °C) exhibit remarkably different solubility in the fluorinated solvent 2H,3H-decafluoropentane, with the solubility higher by a factor of ca. eight for polymorph I at ambient temperature. Structural information established from powder X-ray diffraction and high-resolution solid-state 13C NMR spectroscopy for polymorphs I and II is reported, including crystal structure determination of polymorph II from the powder X-ray diffraction data. Differential scanning calorimetry and high-temperature powder X-ray diffraction demonstrate that the metastable polymorph I converts to the stable polymorph II over a range of elevated temperatures. The combined evidence of these and other techniques suggests that there is a monotropic relationship between polymorphs I and II.