A study of the physicochemical properties and structure of moxifloxacin complex with methyl-β-cyclodextrin

The physicochemical properties and structure of moxifloxacin?methyl-β-cyclodextrin complex have been studied by UV spectroscopy, FTIR spectroscopy, and computer simulation. The optimal conditions for the formation of the complex have been determined, and the dissociation constant of the complex in acidic media (K _dis = (5.0 ± 0.3) × 10^–5 М) has been obtained. It has been found that complexation significantly slows down the release of the drug in acidic media. Experimental results are in good agreement with computer simulation data. The following mechanism of complex formation has been proposed: the incorporation of the aromatic fragment of moxifloxacin into the cavity of methyl-β-cyclodextrin is followed by additional stabilization of the complex via multiple hydrophobic interactions and hydrogen bonding.     

Effect of β-cyclodextrin complexation on physicochemical properties of zaleplon

The physicochemical properties and dissolution profile of zaleplon (ZPN) β-cyclodextrin (βCD) inclusion complex were investigated. The phase solubility profile of ZPN with β-cyclodextrin was classified as A_L-type. Stability constant with 1:1 molar ratio was calculated from the phase solubility diagram and the aqueous solubility of ZPN was found to be enhanced by 714% (p < 0.001) for β-cyclodextrin. Binary systems of ZPN with βCD were prepared by kneading method. The solid-state properties of complex were characterized by differential scanning calorimetry, Fourier transformation-infrared spectroscopy and powder X-ray diffractometry. It could be concluded that ZPN could form inclusion complex with β-cyclodextrin. The dissolution profile of inclusion complex was determined and compared with those of ZPN alone and its physical mixture. The dissolution rate of ZPN was significantly increased by complexation with βCD, as compared with pure drug and physical mixture.     

Structure and energy of formation of β- and γ-cyclodextrin complexes with amino acid enantiomers

The interaction between cyclodextrins (CyD), β-CyD, and γ-CyD, and the L- and D-optical isomers of several amino acids (Ala, Leu, His, Phe) are calculated using DFT. It is found that the L-forms of the investigated amino acids bond more strongly to CyD, due to the different numbers of hydrogen bonds that form. The structures of the resulting complexes are analyzed.     

The structural analysis of the inclusion complex of β-cyclodextrin with m-nitrophenoxyacetic acid

The inclusion complex of β-cyclodextrin with m-nitrophenoxyacetic acid was studied by single crystal X-ray diffraction,2D NMR spectroscopy and semi-empirical methods AMI.The crystallographic study shows that two β-cyclodextrins are held together by hydrogen bonds to form head-to-head dimers.The disordered guest molecule adjusts itself to attain the most stable accommodation into the cavity in which the nitro group is located at the dimer interface while the carboxyl group is buried in the primary hydroxyl groups of β-cyclodextrin.The guest inside the cavity is disordered over two sites and exhibits mobility.Moreover,2D NMR spectroscopy and theoretical study show the same inclusion behavior.In comparison to the inclusion complex of β-cyclodextrin with p-nitrophenoxyacetic acid,the host-guest stoichiometries are different,i.e.,2:1 for m-nitrophenoxyacetic acid and 1:1 for p-nitrophenoxyacetic acid,while the inclusion orientation and the packing pattern of the host are similar in both complexes.     

Thermogravimetric properties of inclusion complexes ofβ-cyclodextrin with benzene,acetylsalicylic acid and methyl salicylate

This paper reports TG analyses of inclusion complexes of-cyclodextrin with benzene, acetylsalicylic acid and methyl salicylate. The data were used for calculation of the compositions of the three body complexes and the apparent kinetic parameters of the thermal decompositions. Water exclusion proceeds as a reaction with ordern=1 and an activation energy about 20 kJ/mol. The expulsion of aromatic guest molecules follows ann=1 order process with the activation energy above 155 kJ/mol, except that for the methyl salicylate complex, which was found to be ca. 64 kJ/mol.     

Effect of γ-irradiation on the physicochemical and sensory properties of hazelnuts (Corylus avellana L.)

The present study evaluated the quality of hazelnuts as a function of irradiation dose to determine dose levels causing minimal undesirable changes to hazelnuts. Physicochemical (color, peroxide value (PV), hexanal content, fatty acid composition and volatile compounds) and sensory (color, texture, odor and taste) properties were determined.Results showed a twenty fold increase in peroxide value and twenty-eight fold increase in hexanal content after irradiation at a dose of 7 kGy. An increase was also observed in saturated fatty acids (10%–23%) with a parallel decrease in unsaturated fatty acids (90–77%). Volatile compounds such as ketones, alkanes, alcohols, aldehydes, furans, aromatic hydrocarbons, bicyclic monoterpenes and acids were produced mostly comprising secondary oxidation products of hazelnut lipids after irradiation. Color parameter b* increased (p<0.05) after irradiation at a dose of ⩾5 kGy, while color parameters L* and a* remained unchanged by irradiation. Sensory evaluation showed that texture and color were not affected by irradiation. Taste, the most sensitive sensory attribute showed that hazelnuts retain acceptable sensory quality when irradiated up to a dose of 1.5 kGy.     

The cavity size effect on the fluorescence properties of 4′-dimethylaminoacetophenone complexed with cyclodextrins

Fluorescence properties of excited 4^′-dimethylaminoacetophenone (DMAAP) complexed with α-, β-, and γ-cyclodextrins (CDs) were studied by means of steady state and time-resolved laser spectroscopy. The 1:2 DMAAP–α-CD and 1:1 DMAAP–β-CD complexes exhibited dual fluorescence in neutral aqueous solutions while only the fluorescence from the locally excited state was observed in the case of DMAAP complexed with γ-CD. The CD cavity size effect on the excited state dynamics of DMAAP–CD complexes was further discussed. It revealed that polarity effect introduced by the hydrophobic cavity is more important in controlling of the photochemistry of DMAAP than the restriction of molecular motion inside the CD cavity.     

The role of maltosyl residue of maltosyl-β-cyclodextrin in the inclusion with dehydrocholic acid

Maltose substituted β-cyclodextrin (M-β-CD) is an important drug carrier due to its excellent water solubility and good compatibility. In this work, dehydrocholic acid (DHA) was taken as the model drug; the inclusion of M-β-CD/DHA was studied through molecular dynamics simulations. The effect of the maltosyl residue of M-β-CD on the interactions of M-β-CD with DHA, M-β-CD with water, and DHA with water were analyzed. Based on the results, the difference between the complex of M-β-CD/DHA and that of β-CD/DHA can be explained and understood.     

Water-soluble γ-cyclodextrin polymers with high molecular weight and their complex forming properties

Polymeric cyclodextrins (CDs) derivatives combine the complex forming properties of CDs and properties of polymers such as high molecular weight and high solubility, justifying the increasing interest for its use in biomedical science. In this paper, a series of water-soluble epichlorohydrin/γ-CD polymers were synthesized and the influences of the epichlorohydrin/γ-CD ratio, NaOH concentration and reaction time were studied in order to get high molecular weight polymers. The M_w distribution and CD content of the polymers were determined by size exclusion chromatography and ¹H NMR, respectively. The complexing properties of the polymers were studied by isothermal titration calorimetry using Methyl Orange (MO) and Sodium Fusidate (Fus) as guests for the γ-cyclodextrin host. The complex formation with MO is exclusively enthalpy driven whereas the one with Fus is totally entropy driven.     

Composition and properties of freeze-dried products of nicotinic acid withβ-cyclodextrin and heptakis (2,6-0-dimethyl)-β-cyclodextrin

The purpose of the study was to examine the formation of inclusion compounds in the freeze-dried products obtained from aqueous solutions of nicotinic acid and -cyclodextrin (-CD), or heptakis (2,6-0-dimethyl)--cyclodextrin (DIMEB). The molar ratios used were 1:1 and 2:1. In addition two freezing temperatures (–40 and –196°C) and different secondary drying temperatures (+50 and +80°C) were used. Freeze-dried products with -CD obtained after low temperature freezing are of the same crystallographic structure as seen in a pure inclusion compound prepared by coprecipitation. Amorphous products were formed after fast freezing. The molar ratios of included nicotinic acid in the freeze-dried products vary — dependent on the preparation conditions — between 0.75:1 and 1:1. A factorial design proves that the included drug amount can be increased by enhancement of the amount of nicotinic acid used, by faster freezing, and by the combination of these two factors. The proof of inclusion formation was given by a combination of X-ray diffractography, differential scanning calorimetry, thermogravimetry and thermofractography.The freeze-dried preparations obtained with DIMEB were amorphous mixtures of the two components. No proof for inclusion of the nicotinic acid in the cyclodextrin cavity could be given. Higher (–40°C) or lower (–196°C) freezing temperatures and the running of the secondary drying process could not influence these results. The very low stability constant of the complex and steric reasons are responsible for this behavior.     

Investigation of the inclusion complex of tolfenamic acid with β-cyclodextrin: Geometry and NBO analysis

Quantum chemical calculations were carried out to investigate geometry and driving forces for inclusion complexes of tolfenamic acid (TA) into β-CD (at 1:1 stoichiometry). Two possible orientations of TA in the β-CD cavity were considered. Both PM3MM and ONIOM2 method evidence that TA is encapsulated in the β-CD cavity for A and B orientation. Finally, charge transfer between the donor and acceptor orbitals of each TA and β-CD play an important role to stabilize the inclusion complex.     

A study of the influence of the conditions of preparation of γ-aluminum oxide as a carrier for reforming catalysts on its physicochemical properties

The formation of highly imperfect γ-Al₂O₃ oxide prepared by calcining pseuodoboehmite and plasticized by organic acids was studied. The nature of the organic acid-aluminum hydroxide plasticizer was found to substantially influence the degree of γ-Al₂O₃ structure imperfection estimated qualitatively as the difference between the X-ray structural density and effective density with respect to helium and aluminum oxide. A high degree of imperfection caused an increase in the intensity of the absorption band at 3775 cm⁻¹ corresponding to OH groups localized on five-coordinate Al³⁺ and the concentration of Lewis acid centers. The adsorption and catalytic properties of systems based on these carriers were studied.     

Improvement of pharmaceutical potential of all-trans retinoic acid with hydroxypropyl-��-cyclodextrin

2-Hydroxypropyl-??-cyclodextrin (HP-??-CyD) includes all-trans retinoic acid (RA), covering the double-bond area of RA with substituted hydroxypropyl groups on CyD ring, as proved by the nuclear Overhauser effect (NOE) between methylene protons on the hydroxypropyl groups and the proton on RA. The formation of an inclusion complex results in hydrophilicity and stability. The effect of RA/HP-??-CyD and that of RA without HP-??-CyD on wrinkle scores and skin elasticity during skin treatment were identical, and the cutaneous stimulus was reduced comparing with RA. The results indicated that the RA/HP-??-CyD complex should help to realize new approaches in skin rejuvenation therapy.     

Concentration dependences of the physicochemical properties of a water–acetone system

Concentration dependences of the UV spectrum, refractive index, specific electrical conductivity, boiling point, pH, surface tension, and heats of dissolution of a water–acetone system on the amount of acetone in the water are studied. It is found that the reversible protolytic interaction of the components occurs in all such solutions, resulting in the formation of hydroxyl and acetonium ions. It is shown that shifts of the equilibrium between the molecules and ions in the solution leads to extreme changes in their electrical properties. It is concluded that the formation of acetone solutions of water is accompanied by heat absorption, while the formation of aqueous solutions of acetone is accompanied by heat release.     

Spectral properties and structures of supramolecular complexes of naphthylpyridine with β-cyclodextrin

The electronic absorption and fluorescence spectra of 4-(2-naphthyl)pyridine (1) and N-methyl-4-(2-naphthyl)pyridinium perchlorate (2 ⁺·ClO₄ ^–) were studied in aqueous solutions in the absence and presence of -cyclodextrin (-CD). In aqueous solutions and organic solvents in the presence of water or H⁺ ions, compound 1 exhibits intense fluorescence with a maximum at 21 270 cm^–1, and its quantum yield in an aqueous solution is 0.9±0.09. The same fluorescence spectrum was detected for an aqueous solution of 2 ⁺·ClO₄ ^–. In an aqueous solution, compound 1 and -CD form stable fluorescing supramolecular 2:2 complexes, whose structure was calculated by the quantum-chemical MNDO/PM3 method. The formation of these complexes induces a hypsochromic shift of the fluorescence maximum of 1 by 5000 cm^–1. The stability constant of the complex is 2·10³ L mol^–1. A decrease in the pH results in the formation of a protonated form of 1(1·H⁺) and destruction of the complex, thus favoring the escape of the substrate from the -CD cavity. The quantum-chemical calculations showed that the insertion of 1 into the -CD cavity is thermodynamically more favorable than hydration; on the contrary, the formation of 1·H⁺ increases dramatically the hydration energy, which promotes the escape of 1·H⁺ from the -CD cavity; cation 2 ⁺ does not form a complex with -CD; in the thermodynamically most favorable 2:2 complex, the naphthalene fragments of two molecules 1 are parallel to each other in a broad section of the -CD dimer constructed according to the head-to-head type.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2420–2425, November, 2004.     

Characterization of the complexation of tauro- and glyco-conjugated bile salts with γ-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin using affinity capillary electrophoresis

The complexation of seven bile salts, present in the small intestine of rat, dog and man, (taurocholate, tauro-β-muricholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate and glycochenodeoxycholate) with γ-cyclodextrin and the chemically modified 2-hydroxypropyl-γ-cyclodextrin, was studied using affinity capillary electrophoresis (ACE). The cyclodextrins (CDs) were investigated due to their use in drug formulation as excipients for solubilisation of poorly soluble drugs and drug candidates. Using mobility shift ACE, the bile salt cyclodextrin interactions were characterized demonstrating 1:1 binding stoichiometry with stability constants ranging from 2 × 10³ to 8 × 10⁴ M^?1. The binding constants showed a systematic dependence on the number and position of hydroxyl groups on the steroid skeleton and the stability constants were in general higher for complexation with the native cyclodextrin than with the modified cyclodextrin. Based upon the size of the complexation constants, it was suggested that the interaction between the CDs and the bile salts takes place at the C and D ring of the steroid skeleton. The complexation of bile salts with the γ-cyclodextrins may compete with drug-γ-cyclodextrin complex formation and, thus, potentially affect drug absorption and efficacy.     

Improvement of pharmaceutical properties of insulin through conjugation with glucuronylglucosyl-β-cyclodextrin

Recently, a large number of peptides and proteins have been utilized as active pharmaceutical ingredients in the clinical field. However, the stability of peptide and protein drugs is often low. In addition, some peptides and proteins adsorb onto glass or polypropylene tube. In the present study, to improve these pharmaceutical properties of peptides and proteins, we newly prepared glucuronylglucosyl-β-cyclodextrin (GUG-β-CyD) conjugate with insulin, a model protein drug, and evaluated its enzymatic or thermal stability and adsorption onto glass or polypropylene tube. The insulin conjugate with GUG-β-CyD was successfully prepared by condensation of amine group of insulin and carboxyl group of GUG-β-CyD. Circular dichroism spectra showed that the secondary structure of insulin in this conjugate was retained. Adsorption of insulin onto glass or polypropylene tube was decreased by the conjugation with GUG-β-CyD. Moreover, enzymatic and thermal stabilities of the conjugate were higher than those of insulin and the mixture of insulin and GUG-β-CyD. These results suggest that insulin conjugation with GUG-β-CyD could improve the pharmaceutical properties of insulin.     

Preparation and characterization of the inclusion complex of baicalein with γ-cyclodextrin: an antioxidant ability study

The formation of the complex of Baicalein with γ-cyclodextrin (γ-CD) was studied by UV–Vis absorption spectroscopy, fluorescence spectra and nuclear magnetic resonance spectroscopy (NMR) in solution. The solid inclusion complex of Baicalein with γ-CD was synthesized by the co-precipitation method. The characterization of the solid inclusion complexes have been proved by infrared spectra. The formation constant (K) of complex was determined by fluorescence method. The results suggested that in different pH solutions, γ-CD has different inclusive capacity to different forms of Baicalein. γ-CD was most suitable for inclusion in neutral media. In addition, the experimental resulted confirmed the existence of 1:1 inclusion complex of Baicalein with γ-CD. Kinetic studies of DPPH? with Baicalein and γ-CD complex were done. The results obtained indicated that the Baicalein/γ-CD complex was the most reactive form. Special configuration of complex has been proposed on NMR technique.