Types Of Cyclodextrins Research Articles

Cyclodextrin polymers for ibuprofen extraction in aqueous solution: recovery, separation, and characterization

Novel cyclodextrin polymers prepared by using citric acid as cross-linked agent were employed for removal of ibuprofen from aqueous solution; five insoluble cyclodextrin polymers with different cyclodextrin types were used. Adsorption tests were carried out, with experimental apparatus consisting of a continuous up flow column. Results of adsorption experiments showed that these polymers exhibited high adsorption capacities toward ibuprofen. Studies concerning the effect of several operating variables (i.e. the effects of contact time, ibuprofen concentration, and mass of adsorbent, pH, and ionic strength) are presented and discussed. Moreover, the extraction of ibuprofen has been studied alone and in a mixture of two pharmaceuticals, and the extraction mechanism was investigated by using numerous methods of characterization.

Mechanism study on pH-responsive cyclodextrin capped mesoporous silica: effect of different stalk densities and the type of cyclodextrin

Cyclodextrin (CD)-capped mesoporous silica nanoparticles (MSN) with pH-responsive properties were synthesized, but little research has been carried out to evaluate the impact of critical factors such as the stalk density and the type of CD on the pH-responsive release behavior. Here, the effect of different stalk densities on the pH-responsive release behavior was investigated. Either too low or too high density of the grafted p-anisidine stalk could result in poor cargo release, and the optimum stalk density for MSN was measured by thermal analysis, and found to be approximately 8.7 stalks nm−2. To achieve effective release control, the CD capes, α-CD and β-CD, were also investigated. Isothermal titration calorimetry (ITC) analysis was employed to determine the formation constants (Kf) of the two CD with p-anisidine at different pH values. The results obtained showed that the complex of β-CD with p-anisidine had excellent pH-responsive behavior as it exhibited the largest changed formation constant (ΔKf) in different pH media. Furthermore, the pH-responsive mechanism between CD and p-anisidine molecules was investigated through ITC and a molecular modeling study. The release of antitumor drug DOX presents a significant prospect toward the development of pH-responsive nanoparticles as a drug delivery vehicle.

Development and Validation of a CD-MEKC System for the Simultaneous Determination of Dihydrostreptomycin Sulfate and Two Benzylpenicillin Salts

A CD-MEKC system using sodium dodecyl sulfate and sulfated-β-cyclodextrin to achieve the simultaneous separation of Penicillin G procaine, Penicillin G benzatine and dihydrostreptomycin sulfate in pharmaceutical and veterinary dosage forms was developed. Several parameters were evaluated, including buffer type and concentration, cyclodextrin type and concentration, and organic solvent and instrumental parameters. The optimized system consisted of 50 mM SDS, 1% sulfated-ß-cyclodextrin, and 10 mM pH 9.0 borate buffer. Capillary temperature was kept at 35°C, and an electrophoretic system was operated under positive polarity at a constant voltage of 18 kV. Validation parameters such as specificity, linearity, LOD, and LOQ, precision, accuracy, and robustness were assayed. Therefore, the developed method was found to be appropriate for quality control of Penicillin G procaine, Penicillin G benzatine, and dihydrostreptomycin sulfate.

Influence of Ethanol as a Co-Solvent in Cyclodextrin Inclusion Complexation: A Molecular Dynamics Study.

Molecular dynamics (MD) simulations were used to investigate the dynamics and host-guest interactions of the inclusion complexes between a potent anti-HIV agent, UC781, and three different types of cyclodextrins (CDs) including βCD, 2,6-dimethyl-βCD (MβCD), and 2-hydroxypropyl-βCD (HPβCD) in aqueous solution with ethanol (EtOH) as a co-solvent. The MD simulation results revealed that EtOH as the co-solvent and the type of cyclodextrin affected the inclusion complex formation. From this study, UC781/MβCD provided the most stable inclusion complex. The competition for the cavity of βCD between UC781 and EtOH and the ensuing occupation of βCD cavities by EtOH resulted in a weaker interaction between βCD and UC781. In HPβCD, a supramolecular complex of UC781−HPβCD−EtOH was formed. The EtOH could easily fill the residual void space of the interior of unoccupied HPβCD due to the movement of UC781. In MβCD, the strong hydrogen bond interactions between the UC781 amide group and the secondary hydroxyl groups of MβCD significantly stabilized the inclusion complex in the presence of EtOH.

Enantiomeric Separation of Sibutramine by Capillary Zone Electrophoresis

The chiral separation of sibutramine enantiomers was resolved succesfully by capillary zone electrophoresis using cyclodextrins (CDs) as chiral selectors. A complex screening of several different native and derivatized, neutral and ionized cyclodextrine derivatives was performed. The effects of buffer type, concentration and pH, cyclodextrin type and concentration, applied voltage, capillary temperature and injection parameters on the chiral resolution were examined. The best results on a very short fused silica capillary of 30 cm × 50 μm were obtained using a 50 mmol L-1 phosphate buffer containing 10 mmol L-1 randomly methylated β-CD at a pH of 4.5, 15 kV of voltage, temperature of 15 °C, injection parameters of 30 mbar s−1 and ultraviolet (UV) detection at 220 nm. The analytical performances of the optimized method were verified in terms of linearity, precision and robustness, and limit of detection and quantification were calculated.

Quality by design in the chiral separation strategy for the determination of enantiomeric impurities: Development of a capillary electrophoresis method based on dual cyclodextrin systems for the analysis of levosulpiride

Quality by design (QbD) concepts, in accordance with International Conference on Harmonisation Pharmaceutical Development guideline Q8(R2), represent an innovative strategy for the development of analytical methods. In this paper QbD principles have been comprehensively applied in the set-up of a capillary electrophoresis method aimed to quantify enantiomeric impurities. The test compound was the chiral drug substance levosulpiride (S-SUL) and the developed method was intended to be used for routine analysis of the pharmaceutical product. The target of analytical QbD approach is to establish a design space (DS) of critical process parameters (CPPs) where the critical quality attributes (CQAs) of the method have been assured to fulfil the desired requirements with a selected probability. QbD can improve the understanding of the enantioseparation process, including both the electrophoretic behavior of enantiomers and their separation, therefore enabling its control. The CQAs were represented by enantioresolution and analysis time. The scouting phase made it possible to select a separation system made by sulfated-β-cyclodextrin and a neutral cyclodextrin, operating in reverse polarity mode. The type of neutral cyclodextrin was included among other CPPs, both instrumental and related to background electrolyte composition, which were evaluated in a screening phase by an asymmetric screening matrix. Response surface methodology was carried out by a Doehlert design and allowed the contour plots to be drawn, highlighting significant interactions between some of the CPPs. DS was defined by applying Monte-Carlo simulations, and corresponded to the following intervals: sulfated-β-cyclodextrin concentration, 9–12mM; methyl-β-cyclodextrin concentration, 29–38mM; Britton–Robinson buffer pH, 3.24–3.50; voltage, 12–14kV. Robustness of the method was examined by a Plackett–Burman matrix and the obtained results, together with system repeatability data, led to define a method control strategy. The method was validated and was finally applied to determine the enantiomeric purity of S-SUL in pharmaceutical dosage forms.

A cleaner production of ultra-violet shielding wool prints

There is an urgent need to reduce the environmental impacts of textile wet processes taking in consideration product and environmental quality as well as economic concerns. Substitution of hazardous chemicals at the source and/or shortening the production steps are potential options which could be used to move towards cleaner production process and to cope with ever-increasing demands for eco-friendly textile products. In this research the possibility of enhancing both the ultra-violet shielding and coloration properties of wool fabric in a single-stage using β-cyclodextrin or monochlorotriazinyl β-cyclodextrin as well as certain ultra violet absorbers or blockers as additives to other environmentally benign printing paste components was investigated. The modified one-step coloration and functionalization method, using safer textile auxiliaries, less energy, and water consumption, proved to have positive impacts on the depth of the obtained prints and their fastness properties as well as on their ability to shield the harmful ultra-violet B-radiation without seriously affecting the environment. The enhancement in the imparted properties is governed by type of cyclodextrin, degree of fixation onto/within the wool structure, type and extent of immobilization of the used ultra violet protector, type of dye and its mode of interaction, as well as degree of interactions among the nominated printing paste components and the wool active sites during the steam fixation step. The imparted ultra-violet protection properties to the modified wool prints show obviously improved durability to wash compared to the unmodified ones.

Enantiomeric separation of tapentadol by capillary electrophoresis—Study of chiral selectivity manipulation by various types of cyclodextrins

The chiral recognition of the centrally acting analgesic agent tapentadol and its isomers with various cyclodextrins (CDs) was studied by capillary electrophoresis, focusing on the migration order of four stereoisomers. In the case of non-charged hydroxypropylated CDs (2-hydroxypropyl-β-CD, 2-hydroxypropyl-γ-CD) the beta derivative was able to discriminate the S,R- and R,S-isomers in acidic background electrolyte, whereas the gamma allowed the separation of S,S- and R,R-tapentadol, respectively. Dual CD system containing both hosts was used to separate all of four isomers. Negatively charged sulfated-α-CD at 1.0% (w/v) concentration in 100mM sodium borate buffer (pH 9.5) was capable of separating the isomers with favorable enantiomer migration order and the optimized method was able to determine 0.15% of chiral impurities of tapentadol in the presence of the last migrating clinically important R,R-isomer.

Solution polymeric optical temperature sensors with long-term memory function powered by supramolecular chemistry.

A poly[(2-ethyl-2-oxazoline)-ran-(2-nonyl-2-oxazoline)] copolymer in combination with hydroxypropylated cyclodextrins has been demonstrated to lead to a supramolecular self-assembly process that results in the formation of kinetically trapped thermoresponsive nanoparticles. Selection of the cyclodextrin type provides control over the nanoparticle phase-transition thermodynamics, thus affording optical temperature sensors with an unprecedented, long-term thermal memory function, which is reversible or irreversible. This research also sheds light onto kinetic and dynamic supramolecular assemblies, thus providing important insight because similar supramolecular processes are at the foundation of living matter.

Aqueous phase synthesis of polysubstituted pyrimidines/pyrrolidines catalyzed by β-cyclodextrin

Highly substituted pyrimidine/pyrrolidine derivatives were synthesized for the first time in water under neutral conditions by the reaction of aromatic amines, dimethyl/diethyl acetylene dicarboxylates, formaldehyde mediated by β-cyclodextrin (β-CD) in good to excellent yields. β-Cyclodextrin can be recovered and reused without any loss of catalytic activity. The β-Cyclodextrins employed were inexpensive and readily available when compared to other types of cyclodextrins (α, γ).

Nanosponges: a potential nanocarrier for novel drug delivery-a review

The ideal delivery system will solubilize the drug, lead the therapy to the target site, and release the therapy to fulfill the individual need of the patient and disease stage. Nanosponges are one of such effective drug carriers which conquer the problems of drug toxicity and poor bioavailability as they can load both hydrophilic and hydrophobic drugs. Nanosponges are tiny in size with a 3-dimensional network and a nanometric cavity size. Nanosponges are highly porous having unique ability to entrap active moieties and offer a unique advantage of programmable release. They are biologically safe and simple to produce. Nanosponges can be prepared by cross linking different types of cyclodextrins with a carbonyl or a dicarboxylate compound as a cross linker. Nanosponge technology has been explored for various applications like enhancing the bioavailability of drug molecules and delivery of drugs into the oral, topical as well as parenteral routes. Nanosponges can also be used as a carrier for biocatalysts in the delivery and release of enzymes, proteins, vaccines and antibodies.

Development and evaluation of vinpocetine inclusion complex for brain targeting

The objective of this paper is to prepare vinpocetine (VIN) inclusion complex and evaluate its brain targeting effect after intranasal administration. In the present study, VIN inclusion complex was prepared in order to increase its solubility. Stability constant (Kc) was used for host selection. Factors influencing properties of the inclusion complex was investigated. Formation of the inclusion complex was identified by solubility study and DSC analysis. The brain targeting effect of the complex after intranasal administration was studied in rats. It was demonstrated that properties of the inclusion complex was mainly influenced by cyclodextrin type, organic acids type, system pH and host/guest molar ratio. Multiple component complexes can be formed by the addition of citric acid, with solubility improved for more than 23 times. Furthermore, In vivo study revealed that after intranasal administration, the absolute bioavailability of vinpocetine inclusion complex was 88%. Compared with intravenous injection, significant brain targeting effect was achieved after intranasal delivery, with brain targeting index 1.67. In conclusion, by intranasal administration of VIN inclusion complex, a fast onset of action and good brain targeting effect can be achieved. Intranasal route is a promising approach for the treatment of CNS diseases.

Fast separation of warfarin and 7‐hydroxywarfarin enantiomers by cyclodextrin‐assisted capillary electrophoresis

The enantioseparation of warfarin and its main metabolite has been achieved using several cyclodextrin types and buffers at different pH, including conditions that have not been attempted so far. Methyl-β-cyclodextrin, highly sulfated-β-cyclodextrin and highly sulfated-γ-cyclodextrin were the most efficient chiral selectors. The pH range, within which particular cyclodextrins support chiral separation, has been approximately determined for the first time. By shortening the effective capillary length to 10 cm, the time of analysis has been vastly reduced <2 min. Hence, baseline separations of warfarin and 7-hydroxywarfarin enantiomers have been achieved in times unreported for those species until now. The established conditions are promising for the further development of new highly selective and fast methods involving warfarin, its derivatives, as well as the same cyclodextrin types.

A comparative study of the effect of α-, β-, and γ-cyclodextrins as stabilizing agents in the synthesis of silver nanoparticles using a green chemistry method

This paper describes the effect of different types of cyclodextrins (CDs) in the synthesis of silver nanoparticles (Ag-NPs), using an easy green chemistry method. The Ag-NPs were obtained using an aqueous silver nitrate solution (AgNO3) with α-, β-, or γ-CDs (aqueous solutions) as stabilizing agents, employing the chemical reduction method with citric acid as a reducing agent. A comparative study was done to determine which cyclodextrin (CD) was the best stabilizing agent, and we found out that β-CD was the best due to the number of glucopyranose units in its structure.The formation of the Ag-NPs was demonstrated by analysis of UV–vis spectroscopy, atomic force microscopy (AFM), scanning electron microscopy–energy dispersive spectroscopy (SEM–EDS) and transmission electron microscopy (TEM). SEM–EDS showed the formation of a cluster with a significant amount of silver, for β-CD-Ag-NPs, spherical agglomerates can be observed. However, for α-, γ-CD, the agglomerates do not have a specific form, but their appearance is porous. TEM analysis shows spherical nanoparticles in shape and size between ~0.5 to 7nm. The clear lattice fringes in TEM images and the typical selected area electron diffraction (SAED) pattern, showed that the Ag-NPs obtained were highly crystalline with a face cubic center structure (FCC).

Novel worm-like amphiphilic micelles of folate-targeted cyclodextrin/retinoic acid for delivery of doxorubicin in KG-1 cells

Folate-targeted cyclodextrin/retinoic acid (CD/RA) conjugate was synthesized using carbonyldiimidazole (CDI) and dimethylaminopyridine (DMAP). The structure of the produced macromolecule was studied by FTIR and 1HNMR. The developed macromolecule could self-aggregate to form micelles. Critical micelle concentration (CMC) of the macromolecule was determined by pyrene as a fluorescent probe. Doxorubicin (DOX)-loaded micelles were prepared by direct dissolution method. To optimize the effect of cyclodextrin type (α or β), the molar ratio of RA to CD and the drug content, a full factorial design was used and their effects on particle size, polydispersity index, zeta potential, loading efficiency (LE%), and release efficiency (RE24%) in 24 h were studied. Orientation of folate ligand on the surface of the micelles was studied by X-ray photoelectron spectroscopy (XPS) technique. The cytotoxicity of DOX-loaded micelles was studied on KG-1 cells which overexpressed folate receptor (FR) and FR-negative HepG2 cells using MTT assay. FTIR and 1HNMR spectra confirmed successful production of the micelles and XPS spectra showed surface orientation of folate. The best results obtained from β-cyclodextrin with molar ratio of 4 to RA and 15 % drug content. The optimized micelles showed the particle size of 103 ± 4 nm, zeta potential of −36 mV, polydispersity index of 0.28 ± 0.05, LE% of 100 %, and RE24% of 69.88 ± 1.6 %. The IC50 of targeted micelles was half of non-targeted micelles and free DOX.

Application of cyclodextrin-based eluents in hydrophobic charge-induction chromatography: Elution of antibody at neutral pH

Hydrophobic charge-induction chromatography (HCIC) has emerged as a useful addition to Protein A chromatography for antibody purification due to its remarkable merits in cost and stability. However, the instability of antibody during acidic elution, which may cause inactivation and aggregation, is still a major concern for the efficiency of this method. The aim of this study is to develop a new strategy of competitive elution with inclusion complexes in HCIC, and to apply it to antibody elution under neutral pH conditions. Interactions between 4-mercaptoethylpyridine (MEP), a typical ligand of HCIC, and four different types of cyclodextrins (CDs) were investigated by molecular docking; immunoglobulin G (IgG) elution capacities of CDs were characterized on MEP-based HCIC mediums. The results demonstrated the general effectiveness of CD-based eluents for HCIC. This type of displacement eluents could allow an efficient elution of bound antibody over a broad range of pH and ion strength. With 15mM β-CD, elution of human IgG was achieved at physiological pH, with an average IgG recovery of 87%. When this elution strategy was used to separate antibody directly from human serum, substantial elution of bound IgG could be obtained at pH 7.4, with product purity comparable to traditional method with an acidic buffer. We expect such method can be of special interest in developing HCIC elution strategy for the proteins like antibody that are sensitive to acidic conditions.

EFFECT OF CYCLODEXTRINS ON THE STABILITY OF BILAYER: A NOVEL ELECTROPHORETIC APPROACH

In capillary electrophoresis, a common approach to prevent adsorption of an analyte onto a capillary's inner surface is to use surfactants as coating materials. These coating materials form a bilayer structure that resembles the arrangement of phospholipids (natural surfactants) in cell membranes. In this study, a bilayer coating was produced on the surface of a capillary using either a double-chained cationic surfactant, dimethyldioctadecylammonium bromide (2C18DAB), or a triple-chained cationic surfactant, tridodecylmethylammonium iodide (3C12MAI). The resulting bilayer coatings were investigated in the presence of various neutral cyclodextrins using hydrodynamic rinsing and performing successive runs. All types of cyclodextrins that were investigated had the effect of partially destabilizing the bilayer. However, cyclodextrin, as well as type of surfactant has a remarkable effect on the extent of a bilayer's stability. The most stable bilayer was obtained on capillaries coated with 2C18DAB using HP-βCD as the running buffer. Under such conditions, reversed EOF (electroosmotic flow) decreased only by 1.5% in over 100 min of electrophoretic separation.

A novel aqueous parenteral formulation of docetaxel using prodrugs

The aim of this study is to develop an aqueous parenteral solution of docetaxel using prodrugs. Docetaxel (DTX) is a highly lipophilic drug and practically insoluble in water. To overcome insolubility of docetaxel, three kinds of docetaxel prodrugs were synthesized using succinyl linker such as DTX-G, DTX-L or DTX-S and physicochemically characterized. The solubility of docetaxel prodrugs was determined by changing the concentration and type of surfactants, cosolvents or cyclodextrins. It was observed that the novel mixture of 15% PEG 400, 2.5% Tween 80 and 20% hydroxypropyl-β-cyclodextrin significantly increased the solubility of DTX-G up to 5.7 mg/mL. After subjected to the study of the hemolytic and cytotoxic activities, it was shown that the novel mixture did not show the hemolysis compared to Taxotere. It was suggested this novel mixture might have the potential to develop an aqueous parenteral formulation.

Aripiprazole-cyclodextrin binary systems for dissolution enhancement: effect of preparation technique, cyclodextrin type and molar ratio.

The aim of this work was to investigate the effect of the natural and the chemically modified form of cyclodextrins namely; β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) respectively on the solubility and dissolution rate of aripiprazole; an antipsychotic medication showing poor aqueous solubility. Phase solubility of aripiprazole with the studied CDs and the complexation efficiency values (CE) which reflect the solubilizing power of the CDs towards the drug was performed. Solid binary systems of aripiprazole with CDs were prepared by kneading, microwave irradiation and freeze-drying techniques at 1:1 and 1:2 (drug to CD) molar ratios. Drug-CD physical mixtures were also prepared in the same molar ratios for comparison. The dissolution of aripiprazole-binary systems was carried out to select the most appropriate CD type, molar ratio and preparation technique. Phase solubility study indicated formation of higher order complexes and the complexation efficiency values was higher for HP-β-CD compared to β-CD. Drug dissolution study revealed that aripiprazole dissolution was increased upon increasing the CD molar ratio and, the freeze-drying technique was superior to the other studied methods especially when combined with the HP-β-CD. The cyclodextrin type, preparation technique and molar ratio exhibited statistically significant effect on the drug dissolution at P≤ 0.05. The freeze-dried system prepared at molar ratio 1:2 (drug: CD) can be considered as efficient tool for enhancing aripiprazole dissolution with the possibility of improving its bioavailability.

Cyclodextrins and Antioxidants

In recent years, the growth of the functional foods industry has increased research into new compounds with high added value for use in the fortification of traditional products. One of the most promising functional food groups is those enriched in antioxidant compounds of a lipophilic nature. In spite of the numerous advantages reported for such antioxidant molecules, they may also have disadvantages that impede their use in functional foods, although these problems may well avoided by the use of encapsulant agents such as cyclodextrins. This explains the recent increase in the number of research papers dealing with the complexation of different guest molecules possesing important antioxidant properties using natural and modified cyclodextrins. This paper presents a review of the most recent studies on the complexes formed between several important types of antioxidant compounds and cyclodextrins, focusing on the contradictory data reported in the literature concerning to the antioxidant activity of the host/guest molecule complexes, the different complexation constants reported for identical complexes, the bioavailability of the antioxidant compound in the presence of cyclodextrins and recommendation concerning the use of natural or modified cyclodextrins. Moreover, the use of cyclodextrins as antibrowning agents to prevent enzymatic browning in different foods is revised. Finally, we look at studies which suggest that cyclodextrins act as ‘‘secondary antioxidants,” enhancing the ability of traditional antioxidants to prevent enzymatic browning.