Polymorphism, pseudopolymorphism, and amorphism of peracetylated α-, β-, and γ-cyclodextrins

Polymorphism, pseudopolymorphism, and amorphism of hexakis(2,3,6-tri-O-acetyl)-α-cyclodextrin (TAαCyD), heptakis(2,3,6-tri-O-acetyl)-β-cyclodextrin (TAβCyD), and octakis(2,3,6-tri-O-acetyl)-γ-cyclodextrin (TAγCyD) were investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and optical microscopy. An anhydrous and a bi-hydrate crystalline forms of TAαCyD, two monotropic anhydrous polymorphs and three pseudopolymorphs (i.e. methanolate, hydrate, and isopropanolate-hydrate) of TAβCyD, as well as two monotropic anhydrous polymorphs and isostructural pseudopolymorphs (e.g. hydrate and isopropanolate-hydrate) of TAγCyD were isolated and characterized. The amorphous forms of each TACyD were also obtained. Thermal data for desolvation of TAαCyD·2H₂O and TAβCyD·CH₃OH were reconciled with their crystal packing features. Melting temperatures and enthalpies of the crystalline forms of each TACyD can be referred to for possible solid-state interactions with drugs.