Β-cyclodextrin Complexes Research Articles

Two Different Approaches for Oral Administration of Voriconazole Loaded Formulations: Electrospun Fibers versus β-Cyclodextrin Complexes.

In this work, a comparison between two different preparation methods for the improvement of dissolution rate of an antifungal agent is presented. Poly(ε-caprolactone) (PCL) electrospun fibers and β-cyclodextrin (β-CD) complexes, which were produced via an electrospinning process and an inclusion complexation method, respectively, were addressed for the treatment of fungal infections. Voriconazole (VRCZ) drug was selected as a model drug. PCL nanofibers were characterized on the basis of morphology while phase solubility studies for β-CDs complexes were performed. Various concentrations (5, 10, 15 and 20 wt %) of VRCZ were loaded to PCL fibers and β-CD inclusions to study the in vitro release profile as well as in vitro antifungal activity. The results clearly indicated that all formulations showed an improved VRCZ solubility and can inhibit fungi proliferation.

Thermal and oxidative stability of Atlantic salmon oil (Salmo salar L.) and complexation with β-cyclodextrin.

The thermal and oxidative stability of Atlantic salmon oil (Salmo salar L.) as well as its β-cyclodextrin (β-CD) complexation ability has been verified for the first time. The main omega-3 fatty acids, EPA and DHA, were significantly degraded, even at 50 °C. Their relative concentrations decrease from 6.1% for EPA and 4.1% for DHA to 1.7% and 1.5% after degradation at 150 °C, respectively. On the other hand, the relative concentrations of monounsaturated and saturated fatty acids remained constant or slightly increased by a few percent after degradation (e.g., from 10.7% to 12.9% for palmitic acid). Co-crystallization of ASO with β-CD at a host–guest ratio of 1:1 and 3:1 from an ethanol–water mixture and kneading methods has been used for the preparation of β-CD/ASO complexes. The analysis of the complexes by thermogravimetry, differential scanning calorimetry (DSC), and Karl Fischer titration (KFT) as well as the decrease of the “strongly-retained” water content confirm the formation of the inclusion compound. Furthermore, the DSC parameters correlate well with the KFT kinetic data for β-CD/ASO complexes.

Characterization of Darunavir: Β-Cyclodextrin complex and Comparison with the Forms of Darunavir Ethanolate and Hydrate

Characterization of Darunavir: Β-Cyclodextrin complex and Comparison with the Forms of Darunavir Ethanolate and Hydrate Darunavir, a protease inhibitor used in the treatment of HIV infection, presents solubility problems and so it was complexed with β-cyclodextrin. Complexation increased the solubility of the drug in more than 28 times compared to the free drug. Then, it is important to characterize this recent advance of pharmaceutical technology as well as its comparison with the forms of free darunavir, hydrate and ethanolate. Spectroscopy in the infrared (IR), thermal techniques of thermogravimetry (TG) and differential scanning calorimetry with heat flux (DSC) and X-ray powder diffraction were elected for the characterization of darunavir:β-cyclodextrin complex and comparison with darunavir ethanolate and darunavir hydrate.

Structure and stability of fluoroquinolone-(2-hydroxypropyl)-β-cyclodextrin complexes as perspective antituberculosis drugs

The formation of host–guest complexes of fluoroquinolones (FQs), such as levofloxacin, ofloxacin, and moxifloxacin with (2-hydroxypropyl)-β-cyclodextrin (HP–β–CD) was studied by spectroscopic methods. The stoichiometry and dissociation constants of the inclusion complexes were determined. The formation of complexes of FQs with HP–β–CD was confirmed by the solubility studies, the UV and FTIR spectra and the equilibrium dialysis. The use of the complex of levofloxacin with HP–β–CD leads to the prolonged release of the former observed in the dialysis experiments. The formation of inclusion complexes makes it possible to increase the solubility of FQs by two to five times. The research may provide a basis for the development of new FQ-containing drugs involving HP–β–CD as a nanocarrier system.

Impact analysis of inclusion complexation on micromeritic properties and dissolution behavior of carvedilol

The study aimed at investigating an inclusion complexation technique to improve solubility and dissolution characteristics of carvedilol by successful complexation with β-cyclodextrin. Inclusion complexes (ICs) of drug and β-cyclodextrin were prepared by kneading method in four different ratios. Physical mixtures were also prepared in identical ratios to compare the efficacy of prepared ICs. The preparations were subjected to rheological studies, drug loading, in vitro release study, FT-IR spectroscopy, thermal events analysis by DSC, X-ray diffraction, scanning electron microscopy (SEM) and accelerated stability study. IC granules were free flowing and compressible. FT-IR study denoted to absence of any chemical interactions between drug and carrier. DSC and X-ray diffraction suggested the presence of crystalline drug in the complexes. Dissolution of ICs revealed significant enhancement of release rate and extent compared to untreated drug. MDT, %DE and T25%, T50% and T80% indicated marked improvement in release rate from complexes. Kinetic modeling suggested that fickian diffusion was the predominant mechanism of drug release from solid complexes. Stability samples showed no significant alterations in DSC and FT-IR studies that referred to the stability of ICs. ICs were compatible, effective and stable over time. Further studies can be planned to investigate their therapeutic efficacy.

Weaving colloidal webs around droplets: spontaneous assembly of extended colloidal networks encasing microfluidic droplet ensembles.

The ability to form transient, self-assembling solid networks that 'cocoon' emulsion droplets on-demand allows new possibilities in the rapidly expanding area of microfluidic droplet-based materials science. In this communication, we demonstrate the spontaneous formation of extended colloidal networks that encase large microfluidic droplet ensembles, thus completely arresting droplet motion and effectively isolating each droplet from others in the ensemble. To do this, we employ molecular inclusion complexes of β-cyclodextrin, which spontaneously form and assemble into colloidal solids at the droplet interface and beyond, via the outward diffusion of a guest molecule (dichloromethane) from the droplets. We illustrate the advantage of such transient network-based droplet stabilization in the area of pharmaceutical crystallization, where we are able to fabricate monodisperse spherical crystalline microgranules of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY), a model hydrophobic drug, with a dramatic enhancement of particle properties compared to conventional methods.

Piroxicam /β-cyclodextrin complex included in cellulose derivatives-based matrix microspheres as new solid dispersion-controlled release formulations

AbstractNew formulations capable to enhance piroxicam (PRX) water solubility and at the same time to control and adjust its release have been developed. For this purpose, two methods have been used and combined to achieve this goal, namely complexation and microencapsulation by O/W emulsion solvent evaporation. In order to modify the drug release, first, microparticles composed of pure PRX and ethylcellulose (EC) or mixtures of EC and hydroxypropylmethylcellulose (HPMC) were prepared, and then, other micropaticles containing the,β-cyclodextrin/piroxicam (,β-CD/PRX) complex obtained by the solvent evaporation technique and EC or a mixture of EC and HPMC were produced and tested. These formulations were characterized by FT-IR, XRD, optical microscopy, and SEM methods. Drug dissolution tests were carried out in acidic media at pH = 1.2 and 37 °C. Depending on the microparticles composition, their size (dio) ranged between 49 pm and 121 pm and PRXioaded varied from 10.8 % to 27.7 %. The effect of complexation and HPMC polymer on the drug release was investigated; the results demonstrated that the Higuchi’s release constant significantly increased when using the EC/HPMC mixture as a matrix with pure PRX or only EC as a matrix with the ,β-CD/PRX complex. The results are remarkably promising since the combination of these processes provided new SD-CR formulations of piroxicam which enabled simultaneous enhancement and control of its release from the carriers.

Highly water-dispersible magnetite nanoparticle supported-palladium–β-cyclodextrin as an efficient catalyst for Suzuki–Miyaura and Sonogashira coupling reactions

A novel highly water-dispersible and recoverable magnetite supported palladium–β-cyclodextrin complex as efficient catalyst in Suzuki–Miyaura and Sonogashira carbon–carbon coupling reactions.

Crystallographic evidence for β-cyclodextrin inclusion complexation facilitating the improvement of antioxidant activity of tea (+)-catechin and (−)-epicatechin

Single-crystal X-ray analysis to 0.6Å resolution using synchrotron radiation of the inclusion complexes of β-cyclodextrin (β-CD) with (+)-catechin (CA) and (−)-epicatechin (EC) has been carried out to gain atomistic insight into how the inclusion complexation helps to improve tea catechin antioxidant activity. The β-CD–CA complex crystallizes in the monoclinic P21 space group, whereas the β-CD–EC complex crystallizes in both the monoclinic P21 and triclinic P1 space groups. In comparing the inclusion structures, the β-CD–EC dimeric structure having higher numbers of OH⋯O hydrogen bonds combined with π⋯π interactions is associated with its greater interaction energy, as derived from DFT/B3LYP single-point energy calculations. Detailed structural analysis of the CA, EC conformation and inclusion geometry reveals that the interplay of the intermolecular OH⋯O hydrogen bond stabilized catechol moiety and the protection of OH groups in the β-CD cavity plays a key role in the improvement of antioxidant capacity upon inclusion complexation.

Facile synthesis of hexagonal-shaped polypyrrole self-assembled particles for the electrochemical detection of dopamine

Nanomaterials have been used as an electroactive medium to enhance the efficiency of bio/chemical sensors, primarily when synergy is reached upon mixing different materials. In this study, we report on the facile synthesis of hexagonal-shaped plate-like polypyrrole (PPY-IC) prepared through inclusion polymerization of the host–guest pyrrole monomeric inclusion complex of β-cyclodextrin (β-CD) to be used in the detection of the neurotransmitter dopamine (DA). The amount of the monomer complex plays a crucial role in the fabrication of well-defined hexagonal-shaped PPY-IC through intermolecular interactions such as π–π interactions and hydrogen bonding between the β-CD and PPY. The microstructure and morphology of the PPY-IC were examined by using various analytical techniques and a tentative mechanism for the growth process proposed which elucidates the formation of the hierarchical structure of the PPY-IC. Cyclo-voltammetry was performed with a PPY-IC modified glassy carbon electrode (GCE) for the electrochemical detection of DA. The concepts behind the novel architecture of the PPY-IC modified electrodes have potential for the production of materials to be used in electrochemical sensors and biosensors.

Nano-encapsulation competitiveness of omega-3 fatty acids and correlations of thermal analysis and Karl Fischer water titration for European anchovy (Engraulis encrasicolus L.) oil/β-cyclodextrin complexes

Abstract European anchovy (Engraulis encrasicolus L.) is one of the most important oily fish that provide valuable omega-3 containing fish oil. The aim of the study was to protect the labile fatty acids from anchovy oil by β-cyclodextrin complexation. The competitiveness to molecular encapsulation of anchovy oil components were also studied. Anchovy oil/β-cyclodextrin complexes at molar ratios of 1:1 and 1:3 were obtained by crystallization and kneading methods with very good recovering yields (74–78% and 85–99%, respectively). The most concentrated fatty acids in the raw anchovy oil were PUFAs at a relative concentration of 65.5 g/100 g. Higher content of EPA and DHA of 28.2 and 22.3 g/100 g had determined. Molecular encapsulation competitiveness conduct to a decrease of the PUFAs (even by five to seven times for EPA and DHA) and a significant increase of saturated fatty acids in complexes. Thermogravimetry and differential scanning calorimetry parameters well correlate with Karl Fischer titration parameters. They also supports the formation of inclusion compound by means of lowering the water content that is replaced by anchovy oil components. As a conclusion, valuable anchovy oil/β-cyclodextrin complexes as well as omega-3 concentrated anchovy oil (non-encapsulated “residue”) can be obtained in one step for food applications.

Inclusion complexes of hydrochlorothiazide and β-cyclodextrin: Physicochemical characteristics, in vitro and in vivo studies

Hydrochlorothiazide is a thiazide diuretic widely used in clinics to treat arterial hypertension. It is a class IV drug according to the Biopharmaceutical Classification System, that is, it presents low solubility and low permeability and, consequently, low absorption in the gastrointestinal tract. As a strategy to improve stability and biopharmaceutical properties of hydrochlorothiazide, the use of cyclodextrins to produce inclusion complexes, applying different methods, was investigated. In the phase solubility studies, β-cyclodextrin was identified as the cyclodextrin which provided the most promising results in terms of the solubilization of the drug. The thermal analysis verified the interaction between hydrochlorothiazide and β-cyclodextrin, indicating the formation of inclusion complexes, and the thermal stability varied according to the preparation technique. The physicochemical characterization showed that in the inclusion complexes obtained by co-evaporation, kneading followed by freeze-drying and kneading followed by spray-drying the hydrochlorothiazide complexation mostly occurred with different degrees of amorphization and the drug solubility was improved. These three inclusion complexes presented better in vitro characteristics and the inclusion complex obtained by kneading followed by freeze-drying increased the in vivo diuretic activity of the drug accompanied by significant effects on natriuresis, kaliuresis and chloriuresis. The inclusion complex formation was effective in improving the biopharmaceutical properties of hydrochlorothiazide and protecting the drug from hydrolysis. This paper describes an important alternative approach to the development of liquid pharmaceutical formulations to pediatric administration, a real need of the current pharmaceutical market.

Utilizing ion mobility and tandem mass spectrometry to evaluate the structure and behaviour of multimeric cyclodextrin complexes

Characterizing noncovalent complexes of molecular dimers and higher complexes using tandem mass spectrometry (MS/MS) can be hindered due to spectral overlap in both the MS and the MS/MS. We investigated the structures and dissociation energetics of multimeric β-cyclodextrin (β-CD) complexes alone or with substrates using combinations of ion mobility spectrometry (IMS), MS/MS, and Rice–Ramsperger–Kassel–Marcus (RRKM) unimolecular rate modelling. The doubly charged β-CD dimers ([(β-CD)2 – 2H+]2−) dissociate to two [β-CD – H+]− ions with the same m/z. IMS was used to separate source generated [(β-CD)2 – 2H+]2− from [β-CD – H+]− and the extent of [(β-CD)2 – 2H+]2− dissociation versus collision energy was determined by modelling changes in the ion’s isotopic profile. The RRKM derived critical energy (E0) for dissociation of [(β-CD)2 – H+]− and [(β-CD)2 – 2H+]2− were 1.85 ± 0.11 eV and 1.79 ± 0.09 eV, respectively, corresponding to a slight decrease in complex stability due to increased charge–charge repulsion in the dianion. This approach was extended to include dimeric complexes complexed to 4,4′-(propane-1,3-diyl) dibenzoic acid (PDDA) and ibuprofen (Ibu).

Inclusion complexation between baicalein and β-cyclodextrin and the influence of β-cyclodextrin on the binding of baicalein with DNA: a spectroscopic approach

This work deals with the commonly studied cyclic oligosaccharide and gains importance as it is entered on a drug delivering carbohydrate and provides insight into the oligosaccharide complex–biomolecular interaction. The binding of a flavone, baicalein, to β-cyclodextrin and calf thymus DNA is studied. The binding of baicalein to calf thymus DNA in the presence of β-cyclodextrin is analysed using the UV–vis absorption and fluorescence spectroscopy. The mode of binding and structure of the baicalein–β-cyclodextrin complex are reported. The role of the structure and the stoichiometry of the inclusion complex of baicalein–β-cyclodextrin in its influence on DNA binding are analysed.Highlights• This paper deals with the binding of a flavone, baicalein to β-cyclodextrin and/or DNA.• The inclusion complexation between baicalein and β-cyclodextrin is analysed.• The stoichiometry and the binding strength of the inclusion complex is reported.• The role of β-cyclodextrin in tuning the binding of baicalein to DNA is emphasized.• Spectroscopic and docking analysis are used to articulate the results.

ENHANCING ANTIFUNGAL CANDIDA ALBICANS ACTIVITY OF Piper bettle LINN. LEAF ESSENTIAL OIL OINTMENT THROUGH FORMATION OF COMPLEX WITH B-CYCLODEXTRIN INCLUSION

The Piper betle leaf essential oil have antimicrobial activity to Candida albicans (Wirna, 2006). However, the essential oil is unstable to high temperature, light, and oxygen. One approach to improve the stability and facilitate in developing various dosage forms is by preparing the essential oil in complex inclusion using β-cyclodextrin (Szejtli, 1989). The aim of the present study was to investigate the effect of inclusion complex formation of the Piper betle leaf essential oil in b-cyclodextrin formulated to polyethylene glicol ointment to antifungal candida albicans activity. The essential oil of Piper betle leaf was isolated by destillation. The inclusion complex of the essential oil - β-cyclodextrin was prepared by coprecipitation of the essential oil : β- cyclodextrin 1:1 (w/w). The inclusion complex formation was studied with thin layer chromatography (TLC) and powder X-ray diffraction (XRD). In the TLC, sillica gel was used as solid phase, whereas toluen-ethyl acetate (7:3) and methanol-water (7:3) was used as mobile phase, then the Rf value of the essential oil and inclusion complex was compared. The XRD pattern of β-cyclodextrin, physical mixtures and inclusion complex was compared, too. Then, the polyethylene glicol ointment of the essential oil and inclusion complex was prepared. The physical properties and antifungal activity was compared. The TLC result showed that the essential oil of Piper betle leaf with methanol-water (7:3) as mobile phase had Rf 0,69 and the inclusion complex had Rf 0,81. With toluen-ethyl acetate (7:3), Rf of the essential oil were 0,63; 0,73; 0,85, whereas the inclusion complex were 0,66; 0,80, and 0,91. The powder XRD analysis showed that the pattern of β-cyclodextrin, physical mixture and inclusion complex were different. The differences of Rf from TLC and XRD patterns were showed that the Piper betle leaf essential oil was complexed with β cyclodextrin. The physical properties studies showed that the homogenity of both formulation was good. The inclusion complex ointment had spreading property, adhering property and antifungal activity which better than the essential oil ointment. The potency of antifungal activity of the inclusion complex of the essential oil - β-cyclodextrin was not significant different than miconazol ointment.

β-Cyclodextrin complexation as an effective drug delivery system for meropenem

Following the preparation of an inclusion complex of β-cyclodextrin and meropenem, methods based on FT-IR, Raman and DSC were used for its characterization. An analysis of changes in the stability of meropenem after complexation showed that the complex may serve as a valuable delivery system significantly contributing to enhanced meropenem stability in aqueous solutions and in the solid phase. Due to a sustained transfer of meropenem from the cavity of the cyclodextrin it was possible to maintain a constant desired meropenem concentration over a period of 20h, as confirmed by a release study. An evaluation of microbial activity not only demonstrated that the bactericidal action of meropenem was not stopped as a result of complexation but even pointed to greater growth inhibition in certain clinically important strains. The fact that investigations of meropenem stability and microbial activity proposed the carbonyl groups as those domains of a meropenem molecule that are instrumental in the formation of a complex with β-cyclodextrin supports the findings of theoretical studies based on molecular modeling.

DFT-ONIOM study of the dopamine–β-CD complex: NBO and AIM analysis

In this work, we conducted a systematic search of the minimum energy of a dopamine–β-cyclodextrin complex via different ONIOM approaches using both mixed (DFT-HF) and nonmixed (DFT-DFT) combinations. Different density functionals were employed: B3LYP, MPW1PW91, M05-2X, M06-2X, and ωB97X-D. Two different basis sets were used on the dopamine–β-cyclodextrin complex; a lower basis set (3-21G*) is used on β-cyclodextrin and a higher basis set (6-31G(d)) is used on dopamine. To fulfill this task, complexation and deformation energies were determined. The relative performance of these functionals was compared with that obtained with the DFT method at the M06-2X/6-31G(d) level that is chosen as a reference method. Although we did not clearly establish an assessment of the relative performance of these density functionals, the efficacy of the ONIOM combination (DFT-HF) is shown compared with a nonmixed ONIOM combination (DFT-DFT). The intermolecular hydrogen bond interactions of the complex obtained with the full M06-2X/6-31G(d) have been analyzed with the atoms-in-molecules and natural bond rrbital methodologies.

β-Cyclodextrin in Water: Highly Versatile and Green Approach for Biomimetic Regioselective Ring Opening of Chalcone Epoxides with Nitrogen Heterocycles

The formation of new C-C bond through highly regioselective ring opening of chalcone epoxides to nitrogen-containing heterocycles has been effectively worked out in impressive yields with heterocyclic nucleophiles such as pyrrole, indole, and 2-methyl indole in the presence of β-cyclodextrin using water as solvent at room temperature within 25–50 min. Water, an environmentally friendly reaction medium, has been utilized for the first time for the reaction of these heterocyclic nucleophiles with chalcone epoxides as their β-cyclodextrin complexes to afford 1,3-diaryl-2-hydroxy-3-(1H-3-indolyl/2-pyrrolyl)propan-1-ones (3a–u). The catalyst can be easily recovered and recycled for several times without loss of activity.

Counterion Anchoring Effect on the Structure of the Solid-State Inclusion Complexes of β-Cyclodextrin and Sodium Perfluorooctanoate

Characterization of the structure and dynamics for the solid inclusion complexes (ICs) between β-cyclodextrin (β-CD; host) and sodium perfluorooctanoate (SPFO; guest) was carried out using 1H/19F/13C NMR spectroscopy. The 1:1 and 2:1 β-CD/SPFO solid complexes were prepared by a modified dissolution method. Evidence for the formation of β-CD/SPFO ICs was provided by 13C DP (direct polarization) and CP (cross-polarization) solid-state NMR spectroscopy with magic angle spinning (MAS) at 20 kHz. The complexation-induced shifts (CIS) of 1H/19F/13C nuclei between solution and the solid state for β-CD/SPFO complexes and the closely related complexes of β-CD/PFOA (perfluorooctanoic acid) were compared. The counterion effect for SPFO and PFOA was observed according to their variable structure and binding as inclusion compounds with β-CD. The effect of sodium versus hydronium counterions on the structure and dynamics of inclusion complexes for these systems was supported by DSC, TGA, FT-IR, and powder X-ray diffrac...

In silico prediction of the β-cyclodextrin complexation based on Monte Carlo method

In this study QSPR models were developed to predict the complexation of structurally diverse compounds with β-cyclodextrin based on SMILES notation optimal descriptors using Monte Carlo method. The predictive potential of the applied approach was tested with three random splits into the sub-training, calibration, test and validation sets and with different statistical methods. Obtained results demonstrate that Monte Carlo method based modeling is a very promising computational method in the QSPR studies for predicting the complexation of structurally diverse compounds with β-cyclodextrin. The SMILES attributes (structural features both local and global), defined as molecular fragments, which are promoters of the increase/decrease of molecular binding constants were identified. These structural features were correlated to the complexation process and their identification helped to improve the understanding for the complexation mechanisms of the host molecules.