Physical properties of the complexes formed between heptakis(2,6-di-O-methyl)-β-cyclodextrin, β-cyclodextrin, and chlorambucil (original) (raw)
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Preparation and solid state properties of cyclodextrin complexes of selected drug molecules
1999
A large number of pharmaceutically important drugs are poorly soluble in water. This study focuses on the 'smart' molecule that can enhance the solubility and hence increase the bioavailability of these drugs. This molecule is a cyclodextrin and is known to form inclusion compounds with various drug molecules. The preparation of P-cyclodextrin CP-CD), y-cyclodextrin (y-CD), heptakis(2,6-di-O-J, methyl)-p-cyclodextrin (Dimeb) and heptakis(:J>•tri-0-methyl)-P-cyclodextrin (Trimeb) 3, complexes with clofibric acid as well as the heptakis(2j•tri-O-methyl)-p-cyclodextrin (Trimeb) complex with clofibrate is reported. The complexes were characterised by thermogravimetric analysis (TG), differential scanning calorimetry (DSC), ultraviolet spectrophotometry (UV), infrared spectroscopy (IR), X-ray powder diffraction (XRD) and single crystal X-ray analysis. Infrared spectroscopy for the four inclusion complexes of clofibric acid showed a significant shift of the C=O stretching frequency in the complexed drug relative to the uncomplexed drug. The crystal structures of the complexes, except that of the Dimeb complex with clofibric acid, were solved. The guest molecules in the P-and y-CD complexes were found to be disordered, preventing detailed interpretation of the mode of inclusion. The guest molecules in the two Trimeb complexes were resolved and the modes of inclusion were revealed. The aliphatic chains of the guests were found to be inserted in the cavity, while the chlorophenyl rings protrude from the secondary side of the Trimeb molecule. Kinetics of dehydration studies for P-and y-CD complexes of clofibric acid, as well as for their
Journal of Inclusion Phenomena, 2002
β-Cyclodextrin (β-CD) and p-hydroxybenzaldehyde (p-HB) were studied by 1 H-NMR in deuterated aqueous solution and the stoichiometry of the resulting complex (1:1) was determined by the continuous variation method. Inclusion of p-HB in β-CD was confirmed by the observation of NMR shifts for the inside H5 protons of the β-CD cavity. In the solid state X-ray analysis was carried out and revealed the detailed structure of the inclusion complex. Two β-CDs cocrystallize with four p-HB and 9.45 water molecules [2(C 6 H 10 O 5) 7 •4C 7 H 6 O 2 •9.45H 2 O] in the triclinic space group P 1 with unit cell parameters: a = 15.262(2), b = 15.728(1), c = 16.350(1) Å, α = 92.67(1) • , β = 96.97(1) • , γ = 103.31(1) •. The anisotropic refinement of 1973 atomic parameters converged at an R-factor = 0.066 for 10157 data with F 2 o > 2σ (F 2 o). The 2:4 stoichiometry for the β-CD inclusion complex with p-HB in the crystalline state is different from that obtained in solution. β-CD forms dimers stabilized by direct O2(m)_1/O3(m)_1• • •O2(n)_2/O3(n)_2 hydrogen bonds (intradimer) and by indirect O6(m)_1• • •O6(n)_2 hydrogen bonds with one or two bridging water molecules joined in between (interdimer). These dimers are stacked like coins in a roll constructing infinite channels where the p-HB molecules are included. The p-HB molecules direct their polar CHO and OH groups into the nonpolar β-CD cavities and are hydrogen bonded to each other, yielding infinite, antiparallel chains. In addition, crystals of the complex were also investigated with thermogravimetry, vibrational spectroscopy (FTIR), and 13 C CP-MAS NMR spectroscopy. The results obtained enabled us to structurally characterize the β-CD inclusion complex with p-HB. * Supplementary data relating to this article are deposited with the British Library as Supplementary Publication No. 82299 (7 pages).
Carbohydrate Research, 2001
The structure of the complex of b-cyclodextrin (cyclomaltoheptaose) with b-naphthyloxyacetic acid was studied in solid state by X-ray diffraction and in aqueous solution by 1 H NMR spectroscopy. The complex crystallizes in the channel mode, space group C2, with a stoichiometry of 2:1; two b-cyclodextrin molecules related by a twofold crystal axis form dimers, in the cavity of which one guest molecule is found on average. The above stoichiometry indicates one guest per b-CD dimer statistically oriented over two positions or two guest molecules in p-p interactions in half of the b-CD dimers and the rest of the b-CD dimers empty. In addition, occupancy of 0.5 for the guest per every b-CD dimer is in accord with the occupancy of the two disordered primary hydroxyls. These two hydroxyl groups, to which the carboxylic oxygen atoms of the guest are hydrogen bonded, point towards the interior of the b-CD cavity. In aqueous solution, the 1 H NMR spectroscopic study indicated that there is a mixture of complexes with host-guest stoichiometries both 1:1 and 2:1.
Acta Crystallographica Section B Structural Science, 2012
The crystal structure of the inclusion complex ofcyclodextrin with lipoic acid was determined from laboratory powder diffraction data. Thermogravimetric data was used to estimate the number of water molecules in the crystal structure. Lipoic acid is included in -cyclodextrin through its primary face with the five-membered ring reaching the center plane of the cyclodextrin cavity and its fatty acid chain adopting a bent conformation. Lipoic acid and -cyclodextrin form a channel-like packing which is stabilized by guest-host hydrogen bonding and close contacts, host-host intermolecular interactions and hydrogen bonding involving the water molecules.
Thermochimica Acta, 2012
An approach mainly based on thermogravimetric analysis (TGA) was developed to evaluate the stoichiometric ratio (SR, guest to host) of the guest-␣-cyclodextrin (Guest-␣-CD) inclusion complexes (4cresol-␣-CD, benzyl alcohol-␣-CD, ferrocene-␣-CD and decanoic acid-␣-CD). The present data obtained from Fourier transform-infrared (FT-IR) spectroscopy showed that all the ␣-CD-based inclusion complexes were successfully prepared in a solid-state form. The stoichiometric ratios of ␣-CD to the relative guests (4-cresol, benzyl alcohol, ferrocene and decanoic acid) determined by the developed method were 1:1, 1:2, 2:1 and 1:2, respectively. These SR data were well demonstrated by the previously reported X-ray diffraction (XRD) method and the NMR confirmatory experiments, except the SR of decanoic acid with a larger size and longer chain was not consistent. It is, therefore, suggested that the TGA-based method is applicable to follow the stoichiometric ratio of the polycrystalline ␣-CD-based inclusion complexes with smaller and shorter chain guests.
Food Chemistry, 2012
The water sorption and physical properties of freeze-dried b-cyclodextrin (BCD) and 2-hydroxypropyl-bcyclodextrin (HBCD) were studied. The stability of the inclusion complexes of these cyclodextrins with different hydrophobic ingredients, such as myristic acid and a-terpineol, was investigated as a function of the storage time and water content of the systems. Besides increasing its solubility, BCD ring modification with hydroxypropyl groups conferred amorficity to the dehydrated matrices, and modified the sorption properties and their ability to form hydrates. Both ligands decreased BCD and HBCD water adsorption, in comparison with the pure cyclodextrins. The water adsorption data and glass transition values obtained are consistent with the displacement of water molecules from the inner cavity of the CDs when the ligand is included. Encapsulation of non-polar ligands of linear hydrocarbon chain, like myristic acid, was initially incomplete, depending on the ligand/CD ratio, and increased with the time of storage and water content.
Carbohydrate Research, 2002
The structure of the complex formed by heptakis(2,6-di-O-methyl)-β-cyclodextrin and (2,4-dichlorophenoxy)acetic acid was studied by X-ray diffraction. The dichlorophenyl moiety of the guest molecule was found outside the host hydrophobic cavity in the primary methoxy groups region whereas the oxyacetic acid chain penetrates the cavity from the primary face. The host molecules stacks along the a crystal axis forming a column.
Studies on the preparation and characterisation of β-cyclodextrin-aceclofenac inclusion complexes
Malay, 2009
Aceclofenac/-cyclodextrin (Ace/-CD) dispersions were prepared to study the influence of -CD on the solubility and dissolution rate of this poorly soluble drug. Phase-solubility profile indicated that the solubility of aceclofenac was significantly increased in the presence of -CD and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Physical characterisation of the prepared systems was carried out by differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and IR studies. Solid state characterisation of the drug in the -CD binary system using XRD, FTIR and DSC revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement of dissolution rate.