Formation Of Β-cyclodextrin Inclusion Complexes Research Articles

Theoretical and Experimental Study of Inclusion Complex Formation of β-Cyclodextrin with Some 1,4-Diazepine Derivatives

Theoretical and Experimental Study of Inclusion Complex Formation of β-Cyclodextrin with Some 1,4-Diazepine Derivatives

Inclusion Complex Formation of β-Cyclodextrin with the Nonsteroidal Anti-inflammatory Drug Flufenamic Acid: Computational Study

Inclusion Complex Formation of β-Cyclodextrin with the Nonsteroidal Anti-inflammatory Drug Flufenamic Acid: Computational Study

Effect of Drug Particle Size on Complexation, Physicochemical Properties and Dissolution of Cyclodextrin Inclusion Complexes

The main purpose of this study was to investigate the role of drug particle size on the complexation, physicochemical properties and dissolution of β-cyclodextrin inclusion complexes. In this work, ibuprofen in size of 3 μm and 45 μm (ibuprofen 3 and ibuprofen 45) were employed as the poorly water-soluble drug model. Complexation kinetics and complexation efficiency studies were conducted to investigate the complexation of ibuprofen with β-cyclodextrin in water. The solid cyclodextrins inclusion complexes were prepared with kneading method and characterized by Fourier transform-infrared spectroscopy, differential scanning calorimetry, X-ray powder difractometry, optical microscopy analyses and dissolution test. Ibuprofen with smaller particle size showed higher complexation rate with β-cyclodextrin in complexation kinetics study. By comparing the apparent stability constant, Kc and complexation efficiency of complexes, it also indicated that smaller drug particles are more efficient to interact with β-cyclodextrin than larger particles. The phase solubility diagram could be classified as Bs type, which denotes complexes with limited solubility. The Fourier transform-infrared spectroscopy, differential scanning calorimetry, X-ray powder difractometry and optical microscopy analyses confirmed the formation of β-cyclodextrin inclusion complexes with ibuprofen 3 or ibuprofen 45. In the dissolution study, the inclusion complexes presented faster dissolution rate on contrast with the physical mixtures and pure drugs. What is more, the inclusion complexes prepared with ibuprofen in small particle size showed improving dissolution rate than in large particle size.

Thermodynamics of β-cyclodextrin–ephedrine inclusion complex formation and covering of nanometric calcite with these substances

Isothermal titration calorimetry (ITC) has been used to characterize inclusion complex formation of β-cyclodextrin (β-CD) with ephedrine in aqueous solutions. ITC measurements were taken at 298.15 K on a MicroCal OMEGA ultrasensitive titration calorimeter (MicroCal Inc.). The experimental data were analyzed on the basis of the model of a single set of identical sites (ITC Tutorial Guide). Based on the experimental values of equilibrium constant (K) and enthalpy of complex formation (ΔH), the Gibbs energy of complex formation (ΔG), and the entropy of complex formation (ΔS), has been calculated. Obtained results showed that β-CD forms inclusion complex of stoichiometry 1:1 with ephedrine and the complex formation is entropy driven. Ephedrine and its complex with β-CD have been further used for covering of the obtained in a controlled way nanometric CaCO3 (calcite), which served as a solid supports for drug depositing. The calcite coating has been analyzed by the use of thermogravimetric method. The size of aggregates of pure calcite particles as well as CaCO3 particles covered by ephedrine and its complex with β-CD have been measured by DLS method. It has been found that pure CaCO3 aggregates are almost monodispersed with the mean diameter equal to 329 nm (±5 nm). Ephedrine and its complex with β-CD layers formed in situ on precipitated calcite surface prevented from crystallites aggregation and decreases particles mean diameter up to 274 nm (±5 nm) for ephedrine and 211 nm (±5 nm) for β-CD complex with ephedrine.

Complexation of β-cyclodextrin with a gemini surfactant studied by isothermal titration microcalorimetry and surface tensiometry.

We report on the inclusion complex formation of β-cyclodextrin (βCD) with a cocogem surfactant (counterion-coupled gemini surfactant; (bis(4-(2-alkyl)benzenesulfonate)-Jeffamine salt, abbreviated as ABSJ), studied by isothermal titration calorimetry (ITC) and surface tension (SFT) measurements. We measured the critical micelle concentration (cmc) of ABSJ in water by the two experimental techniques in the temperature range 283-343 K, and determined the thermodynamic parameters of the complex formation directly by ITC and indirectly by the SFT. The stoichiometry (N), the binding constant (K), and the enthalpy of complexation were determined, and the Gibbs free energy and the entropy term were calculated from the experimental data. A novel method is presented for the determination of N and K by using surface tensiometry.

Inclusion complex formation of β-cyclodextrin and Naproxen: a study on exothermic complex formation by differential scanning calorimetry

Inclusion complex formation between β-cyclodextrin and Naproxen was investigated using differential scanning calorimetry (DSC) as a function of the β-cyclodextrin-to-Naproxen molar ratio, ranging from 0:5:1 to 5:1. When these mixtures are heated above the melting temperature of Naproxen, an exothermic peak is observed at a temperature slightly higher than the melting peak of Naproxen. This peak, which has not been previously reported, has been interpreted as an exothermic energy of inclusion complex formation. The magnitude of this complex formation peak was found to be dependent upon the composition of the β-cyclodextrin and Naproxen mixture and increased in magnitude to a maximum value at a β-cyclodextrin:Naproxen molar ratio of 2:1. In addition, Naproxen recrystallization and re-melting peaks seen in the cooling and re-heating scans, respectively, decreased in magnitude with increasing molar ratio and totally disappeared for the mixture with 5:1 of β-cyclodextrin to Naproxen ratio indicative of complete inclusion of Naproxen in the cyclodextrin cavities. Complete inclusion was further reflected by the disappearance of key Naproxen peaks in Fourier transform infrared spectra of samples recovered from DSC experiments. The large excess of β-cyclodextrin needed to fully complex the Naproxen was found to be due to slow kinetics. Increasing the hold time after the initial melting led to inclusion efficiencies up to 95 % even for the 2:1 mixture. These experiments suggest that ratios of β-cyclodextrin:Naproxen 2:1 or greater facilitate the process by increasing the presence of cyclodextrin molecules in the close proximity of the drug molecules and lead to high inclusion efficiencies.

Thermodynamics of formation of β-cyclodextrin inclusion complexes with four series of surfactant homologs

We report on a titration microcalorimetric study of the formation of β-cyclodextrin inclusion complexes with the members of series of anionic, cationic, and nonionic surfactant homologs containing even numbers of carbon atoms in the alkyl chains. n-Alkyltrimethylammonium bromides (CxTAB, x = 6–16), sodium n-alkyl sulfates (SCxS, x = 6–12), sodium n-alkanesulfonates (SCxSN, x = 6–12), and N,N-dimethylalkylamine-N-oxides (DCxAO, x = 8–12) were selected for use. The stoichiometry, the binding constant, and the changes in enthalpy, entropy, and Gibbs free energy of the complexation reactions were determined at 298 K. It was found in each case that the complexation is favored by both the enthalpy and the entropy changes and that the thermodynamics of the process is affected far more strongly by the length of the alkyl chain than by the nature of the headgroup.

Thermodynamics of inclusion complex formation of β-cyclodextrin with a variety of surfactants differing in the nature of headgroup

The inclusion complexation of β-cyclodextrin with various surfactants, possessing the same alkyl chain length but differing in the hydrophilic headgroup, was investigated by isothermal titration microcalorimetry. Sodium dodecyl sulfate, sodium dodecyl sulfonate, dodecyltrimethylammonium bromide and dodecyl(dimethyl)amine oxide were investigated. The major aim of this study was to elucidate the effects of temperature and the nature of the headgroup on the complex formation. Thermometric titrations were effected between the temperatures (288 and 348)K. The results provided the stoichiometry, the equilibrium constant and the reaction enthalpy of complexation. Changes in Gibbs energy, entropy and van’t Hoff enthalpy were additionally calculated.

Development of Micellar Novel Drug Carrier Utilizing Temperature-Sensitive Block Copolymers Containing Cyclodextrin Moieties

A drug-delivery system for albendazole (ABZ) based on β-cyclodextrin has been synthesized. Well-defined statistical copolymers, composed of N-isopropylacrylamide (NIPAAM) and trimethylsilylpropargyl acrylate (TMSPA), have been prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. The reactivity ratios were determined to be rTMSPA = 1.12 and rNIPAAm = 0.49, in the absence of RAFT agent, and rTMSPA = 1.35 and rNIPAAm = 0.35, in the presence of RAFT agent using the average of different techniques. Block copolymers were prepared using a POEGMEA40 macro-RAFT agent chain extended with NIPAAm and TMSPA in various feed ratios. After deprotection, the polymers were reacted with 6I-azido-6I-deoxy-β-cyclodextrin via Huisgen azide–alkyne 1,3-dipolar cycloaddition, resulting in thermo-responsive block copolymers with pendant β-cyclodextrin groups, which were then acetylated to modify the polarity and inclusion-complex formation of β-cyclodextrin with the drug albendazole (ABZ). Only block...

Effects of Substituent and Solvent on Inclusion Complexation of β-Cyclodextrins with Azobenzene Derivatives

The equilibrium constants (K) for the inclusion complex formationof β-cyclodextrin (β-CD) with Methyl Orange (MO) and substituted azoanilinium chlorides were determinedspectrophotometrically. Based on the results, the substituent effecton the inclusion complexation of β-CD with azoanilinium chlorides was discussed indetail. Further, the solvent effects on the inclusion complexation of MO with β-CD andheptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) wereexamined in aqueous organic mixtures with water-miscible organic compounds(dimethylsulfoxide, acetonitrile, N,N-dimethylformamide, and acetone). It was found that the K value for the inclusion complexformation with β-CD and DM-β-CD decreases remarkably with increasing ratioof organic solvents, dependent of the surface tension of solvent mixtures.

Separation of R- and S-Thalidomide by Reversed-Phase HPLC with ?-cyclodextrin in the mobile phase

R- and S-Thalidomide were resolved by reversed-phase HPLC on a C-18 column with β-cyclodextrin in the mobile phase. As the concentration of β-cyclodextrin was increased stepwise from 0 to 20 mM, enantiomeric resolution increased and retention times decreased significantly. The influence of different organic modifiers in the mobile phase were evaluated, and ethanol, among others, proved to be effective. Equilibrium constants for the formation of β-cyclodextrin inclusion complexes of R- and S-thalidomide in EtOH-buffer (5:95) were calculated to be 64 and 76 M−1, respectively. © 1996 Wiley-Liss, Inc.

The Effects of β-Cyclodextrin On the Fluorescence, Uv Absorption and Solubility of Selected Bimanes In Aqueous Solutions

Abstract The effects of β-cyclodextrin were investigated on the fluorescence emission and excitation as well as on the UV absorption and solubility of certain bimanes in aqueous solution. Three syn-bimanes with differing water solubilities were examined, namely, syn-(CH2OCOCH3, CH3) bimane, syn-(CH3, CH3) bimane, and syn-(C6H3, Cl) bimane. the anti-(CH3, CH3) bimane was also examined. In dilute solutions, the syn-(CH3, CH3) bimane and syn-(C6H3, Cl) bimane showed enhancement of their relative fluorescence intensities upon the addition of β-cyclodextrin as did anti-(CH3, CH3) bimane. Only the anti-(CH3, CH3) bimane showed significant changes in its UV absorption upon the addition of β-cyclodextrin. Both syn-(CH2OCOCH3, CH3) bimane and syn-(CH3, CH3) bimane solubilities were increased in the presence of β-CD. the formation of β-cyclodextrin inclusion complexes is proposed as a possible interpretation of these observations.

Separation of drug stereoisomers by the formation of beta-cyclodextrin inclusion complexes.

For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized beta-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as beta-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of beta-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of beta-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.