amylose and amylopectin. Both are glucose polymers, but amylose is of linear, helical structure due to the α-1→4 glycosidic bonds, while amylopectin has branched configuration. Cyclodextrins (CDs) are produced from the amylose helices maintaining α-1
safety profiles evaluated cyclodextrins (CDs) to own safe uses with agro-chemical manufacturing that should be submitted to environmental protection ( Mitchell and Armstrong, 2004 ; Liu et al., 2011 ; Gruiz et al., 2011 ; Betrand et al., 2011
cyclodextrins (CDs), crown ethers, calixarenes, and cucurbiturils. The supermolecule CDs are macro-cyclic oligosaccharides from the degradation of starch by bacterial enzymes, for example, β-CD and γ-CD have 7 or 8 d -glucose units, respectively. Compared with
Natural crystalline (α-, β-, γ-) and amorphous derivative (hydroxypropyl-β- and methyl-β) cyclodextrins were selected as potential
carriers for obtaining, through a co-grinding technique, a stable activated amorphous form of glyburide with improved dissolution
properties. Differential scanning calorimetry (DSC) was used to investigate solid-state modifications of the drug induced
by co-grinding with the selected carriers in a high energy vibrational micro-mill. X-ray powder diffraction and FTIR spectroscopy
were employed as additional techniques to support DSC data. Equimolar drug : cyclodextrin physical mixtures were co-ground
for different times (up to 60 min) at constant vibration frequency (24 Hz). A progressive drug amorphization with increasing
grinding time was observed in all binary systems, but, interestingly, different degrees of sensitivity to the mechanical-chemical
activation were evident. In fact, blends with natural cyclodextrins, despite the initial higher crystallinity than those with
the amorphous derivatives, required the same or shorter co-grinding times (60 min) to achieve complete drug amorphization.
Stability studies indicated no appreciable drug recrystallization in co-ground products after 4 months storage in sealed containers
at 25°C or 1 month at 25°C and 75% RH. No stability differences were detected between products with natural or derivative
cyclodextrins. The results accounted for the suitability of cyclodextrin co-grinding technique to obtain and stabilize glyburide
in the activated amorphous form.
The enthalpies of solution of α- and β-cyclodextrins is aqueous peptide solutions were determined experimentally at 298.15
K. The obtained results were used to calculate pair cross interaction parameters between solutes. The results are discussed
in terms of the likelysolute–solute interactions. For systems α-cyclodextrin+peptide and β-cyclodextrin+peptide the diametrically
opposite character of interaction defined by structure and solvation of the molecules is observed.
In the present study the solid and liquid phase behaviour of mandelic acid cyclodextrin systems were studied. The samples were prepared using dry grinding/kneading technique in the absence of any solvent. Thermoanalytical methods (TG, DSC, EGD) were used to characterise the solid compounds. In liquid phase the stoichiometry and the stability constants of the complexes formed were determined using UV spectrophotometry. Partial complex formation was found in case of all cyclodextrins used. The amount of uncomplexed mandelic acid varied between 10–20% of the total guest content.
Summary Thermoanalytical techniques (TG, DSC) are frequently used in the investigation of the thermal properties of cyclodextrins and their inclusion complexes. However, the above techniques do not provide information on the chemical composition of the evolved fragments upon the thermal decomposition. In this study &-, &- and &-cyclodextrins and 4 methylated and 3 ethylated &-CD derivatives were investigated with a TG-MS combined thermoanalytical technique in order to get information about their fragmentation behaviour. By comparison of the TG/DTA curves, a different thermal behaviour was found for each of the native and the chemically modified cyclodextrins. Except for the water loss profiles and the solid-solid phase transformations, the thermal behaviour of the (investigated) native CDs do not show remarkable differences. However, the chemical modification of the native &-CD resulting in a new compound may change the strength of interactions between host and guest causing differences in the thermal stabilities of the derivatives. The mass spectrometry results supported the observed thermal differences and showed significant alterations in the fragmentation of ethylated and methylated compounds. The investigated natural CDs possess a very similar fragmentation profile, due to the common &-D-glucopyranose building units. In the case of modified CDs characteristic signals of the substituents are present.
Density and heat capacity of the water+cyclodextrin (CD), water+nicotinic acid (NA) and water+CD+NA mixtures were determined
at 298.15 K. CDs with different cavity size and alkylation were selected. From the experimental data the apparent molar properties
were calculated. Assuming the formation of inclusion complexes of 1:1 stoichiometry, these properties were modeled and provided
the stability constants of CD/NA inclusion complexes and the corresponding property change. The binding of NA with the smallest
sized α-cyclodextrin (α-CD) generates more stable complexes accompanied by the lower volume and the heat capacity changes.
These results are in agreement with earlier proposed binding mode according to which deep insertion of NA into α-CD takes
place and it is governed by the hydrophobic-hydrophilic forces. The volume and the heat capacity changes caused by the interactions
of CDs with NA were interpreted in terms of cosphere overlap model and the release of water molecules from the CD cavity due
to the NA incorporation.
Interactions of native and modified α- and β-cyclodextrins with nicotinic acid, pyridoxine and pyridoxal were studied by isothermal
titration calorimetry, solution calorimetry, and 1H NMR spectroscopy at 298.15 K and pH 6.8. Weak 1:1 complex formation was found only between α-cyclodextrin and nicotinic
acid. The stability constant and corresponding thermodynamic parameters of complex formation (ΔcG, ΔcH and ΔcS) were calculated using the calorimetric data. The 1H NMR data indicate the shallow insertion of the carboxylic group of the nicotinic acid molecule into α-CD cavity. For all
other compounds the weak interactions, not accompanied by complex formation, were characterized by the enthalpic virial coefficients
calculated on the basis of McMillan-Mayer approach. The obtained thermodynamic parameters were analyzed in the terms of influence
of the solutes’ structure on the selectivity of intermolecular host-guest interactions.
The enthalpies, entropies and Gibbs energies of inclusion of dl-1,3-, 1,4- and meso-2,3-butanediols into α- and β-cyclodextrin cavities from ideal gas phase have been determined on the basis of newly obtained
experimental data of the butanediols. The butanediol molecules are stabilised strongly in the cavities due to interactions
with inner walls of the cavities. Entropies of the gaseous isomers are greatly decreased in the cavities. The largest decrease
is obtained for the case of 2,3-BD. Discussions concerning the1,4-butanediol given in the preceding paper have been changed
due to the adoption of new data on the butanediols.