New Polymorph of β-Cyclodextrin with a Higher Bioavailability

A new polymorph of anhydrous β-cyclodextrin (polymorph III) was obtained and characterized for the first time using powder X-ray diffraction, infrared spectroscopy, and thermal analysis. The solution enthalpy and time of dissolution in water were determined using solution calorimetry for this polymorph and compared with those of the dried commercial form of β-cyclodextrin (polymorph I), its amorphous form, and 2-hydroxypropyl-β-cyclodextrin. The specific heat capacities of polymorphs I and III were determined using differential scanning calorimetry across a wide range of temperatures, providing enthalpy and Gibbs energy values for the polymorphic transition at 298 K. The affinities of polymorph III and 2-hydroxypropyl-β-cyclodextrin for water were characterized by determining their hydration isotherms, which provided values of hydration Gibbs energy. Being energy-rich, the new-found polymorph of β-cyclodextrin has a significantly higher dissolution rate and an increased affinity for water compared with the dried commercial form of β-cyclodextrin. These properties render the new polymorph promising in industrial applications for guest inclusion in aqueous solutions and pastes, and may be a desirable alternative for water-soluble β-cyclodextrin derivatives

Determination of Melting Parameters of Cyclodextrins Using Fast Scanning Calorimetry

The first evidence of native cyclodextrins fusion was registered using fast scanning calorimetry (FSC) with heating rates up to 40,000 K s−1. The endothermal effects, detected at low heating rates, correspond to the decomposition processes. Upon the increase of the heating rate the onset of these effects shifts to higher temperatures, reaching a limiting value at high heating rates. The limiting temperatures were identified as the melting points of α-, β- and γ-cyclodextrins, as the decomposition processes are suppressed at high heating rates. For γ-cyclodextrin the fusion enthalpy was measured. The activation energies of thermal decomposition of cyclodextrins were determined by dependence of the observed thermal effects on heating rates from 4 K min−1 in conventional differential scanning calorimetry to 40,000 K s−1 in FSC. The lower thermal stability and activation energy of decomposition of β-cyclodextrin than for the other two cyclodextrins were found, which may be explained by preliminary phase transition and chemical reaction without mass loss. The obtained values of fusion parameters of cyclodextrins are needed in theoretical models widely used for prediction of solubility and solution rates and in preparation of cyclodextrin inclusion compounds involving heating

Unusually High Efficiency of β‑Cyclodextrin Clathrate Preparation by Water-Free Solid-Phase Guest Exchange

An effective preparation procedure is offered for β-cyclodextrin (bCD) clathrates with volatile guests of moderate hydrophilicity, which otherwise require a finely tuned optimization of the bCD/water/guest ratio. The proposed procedure includes guest exchange in a water-free bCD matrix. As a result, more stable clathrates with a higher inclusion capacity can be prepared than by direct saturation of dried or hydrated bCD. To find an optimal preparation method, the structure–property relationships were studied for four different ways of bCD clathrate formation with guests of varying molecular structure. The study was much simplified by used procedures excluding direct contact of guest and water liquids with bCD. Besides, in clathrate preparation experiments, the thermodynamic activities of water and guest were varied independently, which makes explicit the role of water in this process. Hydration of bCD reduces its inclusion threshold for hydrophobic guests by their activity (relative vapor pressure), giving favorable hydration effect for their inclusion. Besides, water competes with hydrophilic guests for binding sites in bCD at high water activities. Together with bCD dehydration by excess of hydrophilic guests, these observations give a complete thermodynamic picture, which may be fruitful for elaboration of guest encapsulation techniques by cyclodextrins