Inclusion Complexation of Carbaryl and β-Cyclodextrin in Solution and in the Solid State

This study was carried out with the aim ofinvestigating the interactions between-cyclodextrin and carbaryl, a carbamatepesticide, and their effect on some physico-chemicalproperties of carbaryl, such as aqueous solubility andlipophilicity. The interactions between carbaryl and-cyclodextrin were thoroughly investigated bothin solution and in the solid state. The effect of-cyclodextrin on the aqueous solubility ofcarbaryl was evaluated by the phase solubility method.The amount of carbaryl dissolved increased linearlywith the addition of -cyclodextrin according toan A_L type plot and without precipitation of thecomplex. The apparent stability constant of thecomplex was 289 ± 21 M^-1, assuming a 1 : 1stoichiometry; this value was confirmed by a methodbased on circular dichroism measurements.Equimolar carbaryl/-cyclodextrin solid systemswere prepared by physical-mixing and freeze-drying,and fully characterised by Differential ScanningCalorimetry, X-ray powder diffractometry and FourierTransform Infra-Red analysis. The results of the solidstate study demonstrated that the freeze-drying methodyields a system with a high degree of amorphisationand yields an inclusion complex.The dissolution profile of the pesticide was affectedby the physico-chemical properties of each solidsystem, the freeze-dried form dissolving more rapidly. However, the physical association of-cyclodextrin and carbaryl enhanced the aqueoussolubility of the insecticide as well.     

Inclusion Modes of Berberine with β-Cyclodextrin in Aqueous Solution

The possible inclusion modes of berberine(Berb)with β-cyclodextrin(BCD)in aqueous solution were predicted by molecular docking,molecular dynamics(MD)simulation and binding free energy calculations.Firs...     

Inclusion Complex of β-cyclodextrin with CTAB in Aqueous Solution

Cetyltrimethylammonium bromide (CTAB)/potassium bromide (KBr) micellar system has been used as a viscosity probe to study the inclusion complexation between β-cyclodextrin (β-CD) and CTAB. Viscosity measurements show that the inclusion complexation between β-CD and CTAB may cause the breakdown of CTAB/KBr wormlike micelles, resulting in the decrease of the solution viscosity. The viscosity minimum at C_β-CD/C_CTAB=2 indicate the molecular ratio of host molecule to guest molecule is 2:1 in the β-CD/CTAB inclusion complex.     

Study of the Podophyllotoxin β-Cyclodextrin Inclusion Complex

The structure of the podophyllotoxin (P)/-cyclodextrin(-CD) inclusion complexhas been studied by infrared spectroscopy, UVspectroscopy, NMR spectroscopy and X-raydiffractometry. The association constant is 128 M^-1in water, calculated from thestraight portion of the phase-solubility diagram.     

Theoretical Study on the Inclusion Complex of β-Cyclodextrin and Nitrobenzene

Quantum chemical calculations were carried out to investigate the structures and properties for the inclusion complexes of nitrobenzene (NB) into β-cyclodextrin. Two low-energy conformations of β-cyclodextrin (A and B) in the gas phase were initially investigated by the PM3 and B3LYP/6-31+G(d,p) calculations, respectively. Three different orientations were considered in the inclusion process of A and B with NB to form 1:1 complexes. Potential energy scan by PM3 calculations indicated that the phenyl orientation Ab for conformation A and the equator orientation Bc for conformation B are more favorable in energy, respectively. We also considered the 2:1 inclusion complexes of host A or B with guest NB in the gas phase. PM3 calculation indicated that the host-guest interaction energies to form 1:1 complexes are more negative than those to form 2:1 NB/B complexes. Finally, we studied the solvent effect of NB/CD complex, and PM3 results show that the influence of water molecules on the inclusion process is very important. The driving forces for the inclusion process and the geometries of complexes were discussed in detail.     

Study on the Structure of Supramolecular Inclusion Complex of β-Cyclodextrin with Retinoic Acid

The importance of Vitamin A for human health has been stressed in resent studies1, meanwhile its derivative so-called retinoic acid (RA) has been widely used as pharmaceutical to treat several types of skin disease and cancer2,3. However the application of retinoic acid is restrained for its poor water solubility, unstability and side effect on the human body.Cyclodextrins (CDs) are macrocyclic oligosaccharides built up from 6, 7, or 8 glucopyranose units called (, (, and (-CD, respectively…     

Stability of Ibuprofen in its Inclusion Complex with β-Cyclodextrin

The ibuprofen--cyclodextrin inclusion complex was prepared by theco-precipitation method. The identity of the obtained product was verified by X-ray and thermogravimetric techniques. The effect of -cyclodextrin on the stability of ibuprofen was analysed.     

Interaction of Naproxen with Crystalline and Amorphous Methylated β-Cyclodextrin in the Liquid and Solid State

Abstract

Interactions of naproxen (NAP) with amorphous, randomly methylated β-cyclodextrin at a degree of substitution per anhydroglucose unit of 1.8 (RAMEB) and with crystalline heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) were studied in aqueous solution and in the solid state using, respectively, phase-solubility analysis (at 25 °C, 37 °C and 47 °C) and differential scanning calorimetry (DSC) supported by X-ray powder diffractometry. RAMEB and DIMEB displayed similar solubilizing and complexing abilities towards NAP, suggesting analogous inclusion modes of the drug in the host cavity in aqueous solution. Differences were instead observed in interactions in the solid state, where the amorphizing capacity of RAMEB toward NAP (evaluated by DSC) was about twice that of DIMEB at each drug-to-carrier ratio. Assuming that inclusion complexation is also involved in solid-state interactions, molecular modelling accounted for the experimental results in terms of structural features of DIMEB, i.e. the particular inwards orientation of O-6-C-8 groups of three alternate glucoses on the primary hydroxyl side which hampers a deep penetration of NAP in the DIMEB cavity in the solid state. On the contrary, no obstruction of the cavity apparently occurs with RAMEB due its noncrystalline state. The aqueous dissolution rate of NAP from NAP-RAMEB and NAP-DIMEB blends containing 0.59, 0.73, 0.85, and 0.92 mass fraction of carrier linearly increased at decreasing drug-to-carrier ratios. The improvement was 5 to 20 times (from powders) and 50 to 200 times (from discs) the dissolution rate of NAP alone for both carrier. Therefore the choice of the amorphous RAMEB in pharmaceutical formulations can be recommended mainly for economic reasons, though the anhydrous and non-hygroscopic nature of crystalline DIMEB might be of particular advantage in case of moisture sensitive formulations.     

Stability of Mefenamic Acid in the Inclusion Complex with β-Cyclodextrin in the Solid Phase

The inclusion complex of mefenamic acid with -cyclodextrin was obtained by the method of coprecipitation from diethyl ether. The product was identified by the thermogravimetric and X-ray methods. The complex stability constants were determined by the potentiometric method. The effect of -CD on the solubility and stability of mefenamic acid was analysed.     

Changes in the Solubility of β-Cyclodextrin on Complex Formation: Guest Enforced Solubility of β-Cyclodextrin Inclusion Complexes

The most common native host molecule, -cyclodextrin (cycloheptaamylose) is able toform inclusion complexes with a large variety of guestmolecules (or ions) of different size and shape. Theproperties of the included guest molecule are highlyinfluenced by the host-guest interaction, and thepractical usefulness of -cyclodextrin isdependent on these effects. These changes are mainlyinvestigated from the point of view of the guest andto a lesser extent from that of the host. In spite ofthis, the kind of guests and that of the host-guestinteractions during the formation of the inclusioncomplex seem to influence the properties of thehydrophilic domain of -cyclodextrin (i.e. thatof the supramolecule itself), too, and this effect canbe well demonstrated by the change of solubility ofdifferent -cyclodextrin inclusion complexes.This change can be best correlated with the solubilityof the guest as if the guest enforced its solubilityon the supramolecule.     

Crystal Structure of β-Cyclodextrin-Felbinac Inclusion Complex

The crystal structure of the inclusion complex of β‐cyclodextrin (β‐CD) synthesized with felbinac (4‐biphenylacetic acid) was determined by single crystal X‐ray diffraction at 150 K. The complex contains two β‐CDs, two felbinac molecules, twenty‐two water molecules in the asymmetric unit, and could be formulated as (C₄₂H₇₀O₃₅)₂·(C₁₄H₁₂O₂)₂·22(H₂O). In the crystal lattice, the two β‐CD moieties form a head‐to‐head dimer jointed through hydrogen bonds, and the felbinacs that interact by face‐to‐face Π‐Π stacking are included in the β‐CD dimer cavity with their carboxyl groups protruding out from cavity opening. In crystals the dimer units of β‐CD are stacked in an intermediate type (IM) that consists of closely packed β‐CD dimer layers.     

Study on the Supramolecular Inclusion Complex of β-Cyclodextrin/Lappaconitine

Lappaconitine (Lap) is a diterpenoid akaliamide, naturally occurring in roots and rhizomes of Aconitum and delphinium. Lap reveals bradycardic, hypotensive, antinocieptive activity. However, its application is restrained owing to its poor water solubility, toxicity and side effects on humans. In a number of pharmaceutical studies,CDs have been reported to interact with many drug molecules to form inclusion complexes. These inclusion complexes have been extensively used to improve water solubility of poorly soluble drugs, to reduce their toxicity, and to increase the dissolution rate [1]. In the present work, the β-CD/Lap complex was prepared by kneading method. The products have been characterized by the solubility measurement as well as UV, FTIR, NMR spectroscopy and X-ray powder diffractometry.     

Aqueous Solution Inclusion of the Nonionic Surfactant C 12 E 4 in β-Cyclodextrin: Implications of Micellization in Stoichiometry Determination and Model Calculations

The inclusion of -n-dodecyl--hydroxytetra(oxyethylene), C₁₂E₄, in -cyclodextrin (CD) has been studied in aqueous solution. Guest encapsulation is recognized by the upfield variations in the chemical shifts of the H3 and H5 inner protons of CD, and the chemical shift differences of the H5 protons are used for determining the complex stoichiometry (2CD : 1C₁₂E₄) by the continuous variation method. Self-association (micellization) of the surfactant molecules is considered, and the relative amount of surfactant involved in micellar systems at the stoichiometric point estimated. A two-layered integrated molecular orbital and molecular mechanics approach with the PM3 and UFF model chemistries for the guest and host, respectively, was used to perform full geometry optimizations and frequency calculations on the host-guest systems. Energies for the optimized structures were subsequently obtained by single point calculations at the Hartree–Fock level using the STO-3G basis set. These calculations showed that one C₁₂E₄ molecule encapsulated by a head-to-head CD dimer is a stable model system in consonance with the experimentally determined stoichiometry, and that the 1 : 1 complex is not stable with respect to dissociation. In the stable 2 : 1 model system, the guest molecule is appreciably tilted with respect to the CD dimer axis and presents a gradually bent alkylic chain in clear manifestation of conformational flexibility. Model calculations for CD inclusion complexes of other oligo(oxyethylene) molecules further indicate that the number and strength of HH intermolecular close contacts reflect the position and conformational flexibility of the guest hydrophobic chain inside CD.     

Inclusion of Enantiomeric Carvones in β-Cyclodextrin: a Variable Temperature 1H NMR Study in Aqueous Solution

In aqueous solution, the apparent association constant at room temperature for the 1 : 1 inclusion of S-(+)-carvone in - cyclodextrin is double of that for R-(-)-carvone, whereas, at 45 °C, both enantiomers have association constants two orders of magnitude smaller, with the S-(+) inclusion being then slightly weaker than the R-(-) encapsulation. Calculations carried out at the molecular mechanics, AM1 and STO-3G levels confirm the preferential inclusion of the S-enantiomer and provide important clues for understanding chiral discrimination by -cyclodextrin.     

Using PVP/SDS Complex as a Probe to Study the Inclusion Complex of β-cyclodextrin with SDS in Aqueous Solution

PVP/SDS complex was applied as a probe to study the interaction between β-cyclodextrin （β-CD） and sodium dodecyl sulfate （SDS） in aqueous solution. It has been found that a critical concentration, namely cs, exists in the relative viscosity of solution containing PVP/SDS complex versus β-CD concentration plot. As the β-CD concentration is less than cs, the relative viscosity of solution decreases sharply by adding β-CD into solution successively. On the other hand, as the β-CD concentration is greater than cs, the relative viscosity of solution increases gradually by adding β-CD into solution. The decrease of the relative viscosity of solution containing PVP/SDS in the presence of β-CD is just due to the inclusion complex of β-CD with the guest molecule SDS. And, this inclusion interaction takes down SDS from the PVP chains in solution. The ratio of the host molecule β-CD to the guest molecule SDS can be calculated from Cs. In our experiment the inclusion ratio of β-CD to SDS is 1/1. The further experimental results indicate that cs is associated with SDS but free from PVP in PVP/SDS complex. However, the inclusion ratio of β-CD to SDS has proved to be independent of either SDS or PVP in PVP/SDS complex.     

Thermodynamic Data for the Complex Formation of Alkylamines and Their Hydrochlorides with α-Cyclodextrin in Aqueous Solution

The formation of complexes between α-cyclodextrin and n-alkylamines and their hydrochlorides has been studied in aqueous solution using calorimetric titrations. All alkylamines form stronger complexes than the corresponding hydrochlorides. The values of the reaction enthalpies are smaller for the alkylamine hydrochlorides compared with the alkylamines. By increasing the number of methylene groups, these differences become smaller. In addition, the reaction enthalpies for protonation of the alkylamines and their complexes with α-cyclodextrin have been measured. The heat of protonation of these complexes is always smaller compared with the alkylamines. Due to the protonation and the formation of a strong solvation shell around the ammonium group the interactions with α-cyclodextrins are weakened. From a thermodynamic cycle using all measured reactions, it can be concluded that the aggregation of the alkylamines with long alkyl chains (heptyl-, octyl-, and nonylamine) has an influence on the values of the reaction enthalpies and entropies for the protonated form only.This revised version was published online in July 2005 with a corrected issue number.     

Pseudorotaxanes of β-Cyclodextrin with Diamino End-functionalized Oligo-phenyl and -benzyl Compounds in Solution and in the Solid State

-Cyclodextrin forms a 1:1 host:guest inclusion complex ([2]pseudorotaxane) with 4-[2-(4-aminophenyl)ethyl]-benzenamine (1) in water as determined by 1D and 2D NMRexperiments. In the crystalline state, the structure of the complex has revealed a 2:2 stoichiometry, with two CD molecules forming head-to-head dimers byH-bonds between the secondary O3 hydroxyl groups and enclosing two molecules of the guest. The packing mode of the present complex is encountered for the first time, since it does not belong to any of the four known packing types of the dimeric CD inclusion complexes. On the other hand,N ¹,N ⁴-bis(4-aminophenyl)-1,4-benzenedimethanamine 2), which is longer than 1 by a phenylene diamine unit, has not afforded any crystals, at present, however it threads into CD in aqueous solution forming most probably [2]- and [3]pseudorotaxanes. The solution structures and the equilibria in this system are investigated.     

Effect of β-Cyclodextrin on the Micellization of Cetyltrimethylammonium in Aqueous Solution at High Temperature

Molar volume and conductivity measurements have been carried out at 338.2 K for cetyltrimethylammonium chloride (CTAC) + H₂O and CTAC + β-cyclodextrin (β-CD) + H₂O systems. The apparent critical micelle concentrations, the dissociation degree of the micelle, the transfer free energy for the hydrocarbon chain of CTAC, the standard partial molar volumes of CTAC in aqueous β-CD solution and the stoichoimetry for the inclusion complex of CTAC with β-CD have been determined. The influence of β-CD and its complex on the micellization processes of CTAC are analyzed under this temperature. It is shown that β-CD partly screened the hydrophobic hydrocarbon chain of CTAC molecules from contact with the surrounding medium, and retarded the formation of CTAC micelles in a certain extent. The thermodynamic activity of CTAC is decreased. The β-CD and its complexes do not participate the formation of micelles of CTAC, and the complex have no effect on the micelle properties once the micelles are formed. Based on a simple model, the number of CH₂ groups entered the cavity of β-CD was calculated. The result suggests that β-CD forms strong complex with CTAC, and the stoichoimetry is found to be 2:1. This supports our conductivity results.