Types Of Cyclodextrins Research Articles

Multicomponent Systems of Econazole with Hydroxyacids and Cyclodextrins

The effect of the type of cyclodextrin (α-, β-, γ-,hydroxypropyl-β-CD) and of hydroxyacid (tartaric, citric, gluconic,malic, lactic) on the solubility enhancement by multicomponent complexationof econazole, a poorly water soluble base-type drug, was studied. A synergisticeffect was found in ternary systems, largely more effective than correspondingbinary complexes and salts. Moreover, the presence of a third component madeeffective the use of γ-CD, which had no solubilizing power in binarysystems. The solubilizing efficiency of multicomponent systems was not relatedto the solubilities of the corresponding salts or binary complexes. Phase-solubility analysis at different temperatures was also used to investigate the interaction of econazole with cyclodextrins, alone or in the presence of hydroxyacid. The best 1 : 1 : 1 molar ratio system was that with α-CD and malic acid which showed the best solubilizing power and the highest stability constant of the ternary complex.Ternary α-CD products, prepared by co-grinding, co-evaporation or colyophilization, were characterized by Differential Scanning Calorimetry and tested for dissolution properties. The higher solubilizing properties of multicomponent systems were reflected in better drug dissolution rates from their solid systems.

Enantioseperation of chiral phenothiazine derivatives in capillary electrophoresis using cyclodextrin type chiral selectors

The enantioseparation of chiral phenothiazine derivatives has been studied in capillary electrophoresis (CE) using various cyclodextrins (CD) such as native α, β, and γ-CD and some of their neutral and charged derivatives. Comparative binding studies were performed using nuclear magnetic resonance (NMR) spectrometry. The advantages and disadvantages of the binding parameters obtained in both techniques (NMR and CE) from the viewpoint of separation optimization are discussed.

Enantioseparation of warfarin by capillary electrophoresis with UV and LIF detection using single and dual cyclodextrin type chiral selectors

The enantioseparation of warfarin (WF) by capillary electrophoresis (CE) has been studied using various cyclodextrins (CD) such as native α,β and γ-CD, several neutral and randomly and selectively substituted charged CD derivatives. The enantiomer migration order of WF was determined with individual CDs. Various, CD combinations were used in order to enhance or diminish the separation factor in a designed way.

Addition of polar organic solvents can improve the product selectivity of cyclodextrin glycosyltransferase. Solvent effects on cgtase.

Cyclodextrin glycosyltransferase (EC 2.4.1.19, CGTase) is an enzyme that produces cyclodextrins from starch via an intramolecular transglycosylation reaction. Addition of small amounts (10% v/v) of polar organic solvents can affect both the overall production yield and the type of cyclodextrin produced from a maltodextrin substrate under simulated industrial process conditions. Using CGTase from Thermoanaerobacter sp. all solvents produced an increase in cyclodextrin yield when compared with a control, the greatest increase being obtained with addition of ethanol (26%). In addition product selectivity was affected by the nature of the organic solvent used: beta-cyclodextrin was favoured in the absence of any solvent and on the addition of dimethylsulphoxide, t-butanol and dimethylformanide while alpha-cyclodextrin was favoured by addition of acetonitrile, ethanol and tetrahydrofuran. With CGTase from Bacillus circulans strain 251 relatively smaller increases in overall cyclodextrin production were achieved (between 5-10%). Addition of t-butanol to a B. circulans catalysed reaction however did produce the largest selectivity for beta-cyclodextrin of any solvent-enzyme combination (82%). The effect of solvent addition was shown not to be related to the product inhibition of CGTase, but may be related to reduced competition from the intermolecular transglycosylation reaction that causes degradation of cyclodextrin products. This rate of this reaction was shown to be dependent on the nature of the organic solvent used.

Simultaneous determination of eleven ingredients in ophthalmic solutions by cyclodextrin-modified micellar electrokinetic chromatography with tetrabutylammonium salt

Cyclodextrin-modified micellar electrokinetic chromatography was applied to determine simultaneously 11 active ingredients in ophthalmic solutions. All the ingredients were successfully separated by using the mixed carrier system containing sodium dodecyl sulfate with β-cyclodextrin and tetrabutylammonium phosphate. The effects of the cyclodextrin type on selectivity were also examined. Excellent separation of the all ingredients was obtained by the use of dimethyl-β-cyclodextrin. The established method was validated and confirmed to be applicable to the determination of the active ingredients in a commercial ophthalmic solution. These results suggest that capillary electrophoresis can be applied to the quantitative analysis as well as qualitative analysis in pharmaceuticals.

Fast development of separation methods for the chiral analysis of amino acid derivatives using capillary electrophoresis and experimental designs

The use of experimental design in method development was studied for the chiral separation of several amino acid derivatives with capillary electrophoresis. The aim of this study was to define rapidly experimental conditions under which the enantiomers can be sufficiently separated for quantification and to derive a methodology for the separation of new compounds. Three modified cyclodextrins (CDs) were used as chiral selectors: hydroxypropyl-β-cyclodextrin, carboxymethyl-β-CD and sulfobutylether-β-CD. The following factors were examined: the type of cyclodextrin, the CD concentration, the pH and the % of organic modifier (methanol) of the electrolyte. Two types of fractional factorial design were used depending on the type of analyte and on the number of factors selected: a 3 4-2 fractional factorial design (4 factors studied at 3 different levels) and a 2 3-1 fractional factorial design (3 factors at 2 different levels). From the 14 compounds investigated, 12 could be separated with one or another CD and not more than 9 experiments were required. No generalisation of the best analysis conditions was possible within this family of compounds. Specific analysis conditions must be defined for each analyte. Experimental designs have shown to be very useful to determine rapidly conditions under which each enantiomer can be separated with an acceptable resolution.

Determination of amitriptyline and nortriptyline in spiked plasma by capillary zone electrophoresis with β-cyclodextrin

A simple capillary zone electrophoresis (CZE) method was developed for the simultaneous analysis of amitriptyline (AMI) and its active metabolite (nortriptyline, NOR) in human plasma. This method was performed by Tris buffer (20 mM, pH 3.0) in the presence of β-cyclodextrin (0.2 mM). Several parameters affecting the separation of AMI and NOR such as the type and concentration of cyclodextrin, pH and concentration of Tris buffer were studied. Application of the method to the analysis of AMI and NOR spiked in plasma was conducted using clomipramine (CLO, 1 nmol) as an internal standard. After liquid–liquid extraction and concentration of AMI and NOR from plasma, the resulting residue was dissolved in aqueous acid prior to their analysis by capillary electrophoresis using UV detection (200 nm). In spiked plasma (1 ml) the quantitative ranges were 160–630 ng for AMI and 150–600 ng for NOR. The intra- and inter-day relative standard deviation ( n=3) were all less than 10% for each substance. The detection limits for plasma samples were found to be about 60 ng/ml for AMI and 70 ng/ml for NOR ( S/ N=3, injection 20 s). All recoveries for AMI and NOR were greater than 80%.

Cyclodextrins in Polymer Synthesis: Supramolecular Cyclodextrin Complexes of Pyrrole and 3,4-Ethylenedioxythiophene and Their Oxidative Polymerization

Cyclodextrins can act as hosts for heteroaromatic compounds to produce stable, odorless, complexes that can be oxidatively polymerized in water, it is reported here. The preparation and structural analysis of ratio 1:1 host–guest complexes for several types of cyclodextrin with pyrrole or 3,4-ethylenedioxythiophene (see Figure), and their reaction in water to give conjugated polymers are presented here (see also cover).

Cyclodextrins in Polymer Synthesis: Supramolecular Cyclodextrin Complexes of Pyrrole and 3,4-Ethylenedioxythiophene and Their Oxidative Polymerization

Cyclodextrins can act as hosts for heteroaromatic compounds to produce stable, odorless, complexes that can be oxidatively polymerized in water, it is reported here. The preparation and structural analysis of ratio 1:1 host–guest complexes for several types of cyclodextrin with pyrrole or 3,4-ethylenedioxythiophene (see Figure), and their reaction in water to give conjugated polymers are presented here (see also cover).

An Overview of Host-Guest Chemistry and its Application to Nonsteroidal Anti-Inflammatory Drugs

The concept of host-guest chemistry has opened the way to the construction of supramolecular (inclusion) complexes with physicochemical properties superior to those of the guest molecule. Several types of host molecules have been synthesised, including crown ethers, cryptands, spherands, carcerands and cyclodextrins. All are able to act as ‘artificial receptors’ and at least partially enclose guest molecules such as cations and drugs. Cyclodextrins are chemically stable, water soluble oligosaccharide hosts derived enzymatically from starch. Because their interiors are relatively lipophilic and their exteriors hydrophilic, cyclodextrins can complex hydrophobic guests to form inclusion complexes in aqueous solution. Of the 3 types of cyclodextrins (α, β and γ), β-cyclodextrin is the best studied. Among the potential advantages of using host-guest complexes in oral drug delivery are enhanced rate and extent of drug (guest) dissolution, and thus improved bioavailability, of poorly soluble drugs. The piroxicam-β-cyclodextrin inclusion complex typifies this: the complex increases the rate of dissolution and absorption of the original piroxicam molecule. Host-guest complexes, for example piroxicam-β-cyclodextrin, provide a means to overcome inherent physicochemical difficulties with numerous chemical and medicinal agents. The future looks likely to bring many more opportunities for host-guest chemistry to play a part in our everyday lives.

Modification of the Physicochemical Properties of Minocycline Hydrochloride Ointment with Cyclodextrines for Optimum Treatment of Bedsore.

Modification to find the best physicochemical properties of minocycline hydrochloride ointment for optimum treatment of bedsore was investigated by coformulating various types of cyclodextrins (CyD) in the ointment base. It was found that the drug release rate from the ointment base was modified according to the preparation method of ointment base and the type of CyD admixed. The physicochemical properties, such as viscosity, elution volume, water absorption of ointment base were also modified by those factors. The mechanism of physicochemical modification with CyD was explained by the structural change of ointment base and the change of surface tension of emulsifying agent solution with the CyD. The stability of ointment was investigated by confirming the reproducibility of drug release rate after storage at ambient and cooled temperature conditions. In conclusion, a fused mixed ointment with beta-CyD was found to be preferable for treatment of bedsore, because of the improved drug release rate, lowered viscosity and increased elution volume of the resultant ointment.

Enantioseparation Of Aromatic Dipeptides Using Carboxymethyl-β-Cyclodextrin Polymer As Chiral Selector By Capillary Electrophoresis

ABSTRACT Chiral separation of peptides is of interest because of the different biological activity of enantiomers. In this report, several underivatized dipeptides with benzene moieties were optically resolved by employing carboxymethyl-β-cyclodextrin polymer(CM-β-CD polymer) as chiral selector. The effects of different cyclodextrin types, selector concentration, buffer pH, and organic additive were examined. Selector concentration and buffer pH played significant roles in resolution. Enantioseparation was found to be negatively influenced by adding the organic additive into running buffer and even completely lost at the organic additive content of 16%. It was also noted that the dipeptides with short chain in the vicinity of the second chiral carbon atom showed better chiral resolution by using CM-β-CD polymer than by using either carboxyethyl-β-CD or succinylated-β-CD. Simultaneous chiral separation of a mixture of DL-Ala-DL-Phe and DL-Leu-DL-Phe was also obtained using 27 mg/ml CM-β-CD polymer in the running buffer at pH5.12.

Enantiomeric and Isomeric Separation of Pesticides by Cyclodextrin-Modified Micellar Electrokinetic Chromatography

Abstract Cyclodextrin-modified micellar electrokinetic chromatography was applied successfully to the enantiomeric and isomeric separation of 7 commonly used pesticides (propiconazole, bioallethrin, fenpropathrin, phenothrin, bitertanol, triadimenol, and dimethomorph). Commercially available surfactants used alone or in combination with cyclodextrins were evaluated for separation of the enantiomers/isomers of the 7 pesticides. The enan-tiomers/isomers of the pesticides used in this study were baseline resolved with resolutions of ≥1.5. The resolution was found to depend on the type of surfactant and cyclodextrin employed in the running buffer. In the case of propiconazole and dimethomorph, baseline resolution was also achieved by adding sodium cholate (a chiral surfactant) alone to the running buffer. Analysis of fortified water samples yielded recoveries ranging from 45 to 89% and method detection limits ranging from 0.18 to 2.1 ppb. The reported capillary electrophoresis methods are simple, rapid, and reproducible.

Rapid development of the enantiomeric separation of β-blockers by capillary electrophoresis using an experimental design approach

A rapid method for determining the separation conditions for chiral resolution of eleven β-blocking drug substances by capillary electrophoresis is described, using an experimental design approach. An acidic phosphate–triethanolamine buffer and an uncoated fused-silica capillary were used for all experiments. Several modified cyclodextrins were applied as chiral selectors: sulfobutyl ether β-cyclodextrin (SBE-βCD), dimethyl β-cyclodextrin (DM-βCD), carboxymethyl β-cyclodextrin (CM-βCD), and hydroxypropyl β-cyclodextrin (HP-βCD). Two different fractional factorial experimental designs were applied: (1) a design examining four factors at three levels (3 4–2) and (2) one examining three factors at two levels (2 3–1). The factors studied were: type of cyclodextrin, cyclodextrin concentration, pH of the background electrolyte and percentage of organic modifier. Enough resolution for the separation of the enantiomers and even for their quantification was reached. The same scheme is proposed when a fast chiral separation method needs to be developed for other drug families.

Enantiomeric separation of atropine in Scopolia extract and Scopolia Rhizome by capillary electrophoresis using cyclodextrins as chiral selectors

We separated the enantiomers of atropine, a main ingredient of Scopolia extract and Scopolia Rhizome, by capillary electrophoresis. The best conditions for chiral separation were investigated based on the concentration and type of cyclodextrin (CD) used, the pH, the concentration of the electrolyte solution and the capillary temperature. Good resolution of d- and l-hyoscyamine (atropine) was achieved in 100 m M phosphate buffer (pH 2.5) containing 30 m M trimethyl-β-cyclodextrin (TM-β-CD) as the chiral selector. The calibration curves showed good linearity in the range of 10–200 μg/ml ( r≥0.99) for d-hyoscyamine, l-hyoscyamine and scopolamine. We could analyze atropine from the samples of crude drugs and pharmaceutical preparations according to the procedures described in The Japanese Pharmacopoeia (Thirteenth Edition).

Determination of formation constants of cyclodextrin inclusion complexes using affinity capillary electrophoresis

The present study describes the application of the method of affinity capillary electrophoresis (ACE) to investigate interactions between five types of cyclodextrins (CD) and model drugs. While the drugs were injected as sample solution, the effect of different CD types and concentrations in the run buffer was studied. Mathematical models were developed to evaluate the inclusion complex formation constants and the mobilities of the complexes. Further stoichiometric constants were determined, and different models for interpretation of these results were suggested. It was evident that size and hydrophobicity of drugs have a stronger influence on the formation of inclusion complexes than the charge of drugs. β-CD and its derivatives show the strongest interactions with drugs. The handling of the described technique as well as the mathematical description are very simple. The evaluation of the different mathematical models yielded similar results. The use of a nonlinear equation enables an improved fit to experimental data. The present results demonstrate that ACE is valuable as a rapid screening method to characterize inclusion complexes between drugs and CDs. ©1999 John Wiley & Sons, Inc. J Micro Sep 11: 215–222, 1999

Cyclodextrins as diethylstilbestrol carrier system: characterization of diethylstilbestrol-cyclodextrins complexes.

The in vitro formation of DES-cyclodextrins inclusion complexes was characterized using lipoxygenase as enzymatic system. DES-cyclodextrins complexes were obtained in aqueous solution. The addition of cyclodextrins to the reaction medium had an inhibitory effect on DES oxidation by lipoxygenase due to the drug's complexation into the cyclodextrin cavity. This inhibitory effect depends on the complexation constant between DES and the cyclodextrins type used. In this case, beta-, 2-hydroxypropyl-beta- and gamma-cyclodextrins have similar complexation constants and therefore produce the same inhibitory effect. Moreover, depending on the type of cyclodextrins used, the solubility of DES can be enhanced up to 956 times, while the lipoxygenase activity remains constant. These results suggest that the system described may be used as a controlled-release delivery system for DES, since it may diminish the local and systemic adverse side effects caused by high concentrations of the drug.

Evaluation of the enantioselective possibilities of sulfated cyclodextrins for the separation of aspartyl di- and tripeptides in capillary electrophoresis

Highly sulfated α-, β- and γ-cyclodextrins were used to investigate the simultaneous separation of isomeric α- and β-aspartyl containing di- and tripeptides as well as their enantiomers in capillary electrophoresis. Separation of the enantiomers was accomplished with the different sulfated cyclodextrin types under acidic conditions (pH 2–3). In some cases, comigration of diastereomerically related isomers or epimers resulted in incomplete separations. The results obtained with the highly sulfated cyclodextrins, having an average degree of substitution 12, were compared to those obtained with sulfated cyclodextrins with degree of substitution 4.

Study of cytokinin separation using capillary electrophoresis with cyclodextrin additives

The separation of a set of 10 cytokinins by capillary electrophoresis was investigated. The influence of various cyclodextrin derivatives (α-, β-, γ-, hydroxypropyl-β- and dimethyl-β-cyclodextrins) in the background electrolyte on the migration characteristics of the compounds investigated was studied. The relationship between the structures of single cytokinins and the type of cyclodextrin used was evaluated. A set of all 10 cytokinins was successfully separated in 100 mmol l −1 phosphate–Tris buffer (pH 2.5) as a background electrolyte under different experimental conditions e.g., with addition of 25 mmol l −1 γ-cyclodextrin.

Determination of the enantiomeric purity of (−) terbutaline by capillary electrophoresis using cyclodextrins as chiral selectors in a polyethylene glycol gel

A method was developed for determination of the enantiomeric purity of the therapeutic-pharmacological active (−)-enantiomer of terbutaline using cyclodextrins as a chiral selector dissolved in a removable liquid polyethylene glycol gel by use of capillary electrophoresis. The effect of temperature, type and concentration of polyethylene glycol and cyclodextrins was studied on the resolution between the two enantiomers. Best results were obtained with 10 mM hydroxyethyl- β-cyclodextrin dissolved in a 10% polyethylene glycol-2000 solution at 15°C. Under these conditions, an impurity of 0.1% (distomer/eutomer) can be readily detected.