Inclusion complex of tamibarotene with hydroxypropyl-β-cyclodextrin: Preparation,characterization, in-vitro and in-vivo evaluation

The goal of this study was to improve the solubility and oral bioavailability of tamibarotene by complexing it with hydroxypropyl-β-cyclodextrin(HP-β-CD).The inclusion complex of tamibarotene with hydroxypropyl-β-cyclodextrin(Am80-HP-β-CD)was prepared through a freeze-drying method at the mole ratio of 1:1(Am80:HP-β-CD).Fourier transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC)indicated the formation of Am80-HP-β-CD.In vitro dissolution studies showed that the solubility and dissolution percentage of Am80-HP-β-CD was improved substantially compared to Am80.An improved dissolution with approximately 97%drug release in 3 min was observed,in comparison with Am80 with approximately 60% release in 45 min.In vivo studies indicated that the AUC0-∞ has increased 2.79 times and the Cmax 4.37 times after the formation of inclusion complex.The decrease of tmaxindicated the Am80-HP-β-CD inclusion complex can be absorbed into blood faster.In short,the solubility and bio-availability of Am80 has notably increased with the complexation of HP-β-CD.Therefore,using the inclusion technique is a promising method to improve the solubility of insoluble drugs.

Enhancement of norfloxacin solubility via inclusion complexation with β-cyclodextrin and its derivative hydroxypropyl-β-cyclodextrin

The objectives of the study were to investigate the effects of β-cyclodextrin(βCD) and hydroxypropyl-β-cyclodextrin(HPβCD) on the solubility and dissolution rate of norfloxacin prepared using three different methods, at drug to cyclodextrin weight ratios of 1:1, 1:2, 1:4 and 1:8. All the methods increased the solubility and dissolution rate of norfloxacin via inclusion complexation with βCD and HPβCD. Norfloxacin was converted from crystalline to amorphous form through inclusion complexation. Solvent evaporation method was the most effective method in terms of norfloxacin solubilisation, while inclusion complex of HPβCD has higher solubility than βCD complex when prepared using the same procedure.

A stepwise optimization strategy to formulate in situ gelling formulations comprising fluconazole-hydroxypropyl-beta-cyclodextrin complex loaded niosomal vesicles and Eudragit nanoparticles for enhanced antifungal activity and prolonged ocular delivery

Fungal keratitis and endopthalmitis are serious eye diseases.Fluconazole(FL)is indicated for their treatment,but suffers from poor topical ocular availability.This study was intended to improve and prolong its ocular availability.FL niosomal vesicles were prepared using span 60.Also,polymeric nanoparticles were prepared using cationic Eudragit RS100 and Eudragit RL100.The investigated particles had adequate entrapment efficiency(EE%),nanoscale particle size and high zeta potential.Subsequently,formulations were optimized using full factorial design.FL-HP-β-CD complex was encapsulated in selected Eudragit nanoprticles(FL-CD-ERS1)and niosmal vesicles.The niosomes were further coated with cationic and bioadhesive chitosan(FL-CD-Nios-ch).EE%for FL-CD-ERS1 and FL-CD-Niosch formulations were 76.4%and 61.7%;particle sizes were 151.1 and 392 nm;also,they exhibited satisfactory zeta potential+40.1 and+28.5 m V.In situ gels were prepared by poloxamer P407,HPMC and chitosan and evaluated for gelling capacity,rheological behavior and gelling temperature.To increase the precorneal residence time,free drug and selected nano-formulations were incorporated in the selected in situ gel.Release study revealed sustained release within 24 h.Permeation through excised rabbits corneas demonstrated enhanced drug flux and large AUC0-6 h in comparison to plain drug.Corneal permeation of selected formulations labeled with Rhodamine B was visualized by Confocal laser microscopy.Histopathological study and in vivo tolerance test evidenced safety.In vivo susceptibility test using Candida albicans depicted enhanced growth inhibition and sustained effect.In this study the adopted stepwise optimization strategy combined cylodextrin complexation,drug nano-encapsulation and loading within thermosenstive in situ gel.Finally,the developed innovated formulations displayed boosted corneal permeation,enhanced antifungal activity and prolonged action.

Synthesis of Hydroxypropyl-β-cyclodextrin Bonded Silica-gel and its Application to Resolution

In order to set up a simple and effective method for resolution of optical isomers, hydroxypropyl-β-cyclodextrin was bonded to silica-gel, which can be used for preparation of thin-layer chromatography plates. Resolution of clenbuterol and propranolol were investigated on these thin-layer chromatography plates using different combinations of solvent systems at ambient temperature. The best simultaneous resolution was achieved in solvent system of acetonitrilen-butanol （50：50, v/v）. Rst values of resolution of clenbuterol hydrochloride and propranolol hydrochloride are 3.6 and 4.3, respectively. The spots of different enantiomers are separated clearly. The results showed that hydroxypropyl-β-cyclodextrin bonded silica-gel could be successful in resolution of chiral adrenergic drugs. The study offers a direct, rapid and reliable method for separation of this kind of optically active compounds.

Preparation and Evaluation of Insulin-loaded Nanoparticles based on Hydroxypropyl-β-cyclodextrin Modified Carboxymethyl Chitosan for Oral Delivery

Novel insulin-loaded nanoparticles based on hydroxypropyl-β-cyclodextrin modified carboxymethyl chitosan（CMC-HP-β-CD） were prepared to improve the oral bioavailability of insulin. The CMC-HP-β-CD was characterized by FT-IR spectroscopy and 1H-NMR spectra. The insulin-loaded nanoparticles were prepared through crosslinking with calcium ions, and the morphology and size of the prepared nanoparticles were characterized by transmission electron microscopy（TEM） and dynamic light scattering（DLS）. Cumulative release in vitro study was performed respectively in simulated gastric medium fluid（SGF, p H=1.2）, simulated intestinal fluid（SIF, p H=6.8） and simulated colonic fluid（SCF, p H=7.4）. The encapsulation efficiency of insulin was up to 87.14 ± 4.32% through high-performance liquid chromatography（HPLC）. Statistics indicated that only 15% of the encapsulated insulin was released from the CMC-HP-β-CD nanoparticles in 36 h in SGF, and about 50% of the insulin could be released from the nanoparticles in SIF, whereas more than 80% was released in SCF. In addition, the solution containing insulin nanoparticles could effectively reduce the blood glucose level of diabetic mice. The cytotoxicity test showed that the samples had no cytotoxicity. CMC-HP-β-CD nanoparticles are promising candidates as potential carriers in oral insulin delivery systems.

Strong Inclusion Complexation Using Hydroxypropyl-β-Cyclodextrin as Host Molecule

Inclusion complexes of nitro-compounds using β-cyclodextrin and hydroxypropyl-β-cyclodextrin as host molecule have been studied by cyclic voltammetric method. The inclusion constants of the corresponding complexes have been determined. Strong inclusion complexation by hydroxypropyl-β-cyclodextrin has been verified

Preparation of Forsythiaside-hydroxypropyl-β-cyclodextrin Inclusion Complex and Its Characters

To overcome the chemical instability of forsythiaside,the forsythiaside-hydroxypropyl-β-cyclodextrin inclusion complex was prepared by triturating. The inclusion complex was found having a varied UV spectrum and melt temperature point. Inclusion complex has a higher stability to UV light and temperature over forythiaside itself. Pharmacological evidence showed that inclusion complex has little effect on pharmacokinetics by chicken intravenous injection. This study is favorable for developing preparations for forsythiaside and its clinical application.

6-O-(Hydroxypropyltrimethylammonia)-β-cyclodextrin with Low Degree of Substitution: Convenient Preparation and its Application as a Chiral Selector in Capillary Electrophoresis

A cationic cyclodextrin derivative 6-O-（hydroxypropyltrimethylammonia）-β-cyclodextrin （GTA-β-CD） with low degree of substitution was prepared through a convenient method in solid phase. The product could be used as a valuable chiral selector in the capillary electrophoresis （CE） separation of some acidic drug enantiomers such as naproxen, ofloxacin, ibuprofen and warfarin.

The protective effect of cyclodextrin on the color quality and stability of Cabernet Sauvignon red wine

The impact of cyclodextrins(CDs)on wine quality and stability remains largely unknown.This study systematically assessed the protective effect of the post-fermentation addition of CDs on color stability of red wine from the viewpoints of color characteristics,copigmentation and phenolic profiles.The grey relational analysis(GRA)and principal component analysis(PCA)methods were employed to dissect the key effective determinants related to color quality.The addition of CDs induced a significant hyperchromic effect of 8.19-25.40%,a significant bathochromic effect and an enhancement of the color intensity.Furthermore,the evolution of anthocyanin forms and the content of monomeric anthocyanins revealed that β-CD is a superior favorable cofactor during wine aging,but for long-term aging,2-HP-β-CD and 2-HP-γ-CD are more beneficial in promoting the formation of polymerized anthocyanins and color stability.This work provides an important reference for the use of CDs to enhance the color quality and stability of red wines.

Solubility Enhancement of Domperidone Fast Disintegrating Tablet Using Hydroxypropyl-<i>β</i>-Cyclodextrin by Inclusion Complexation Technique

Domperidone Maleate (DOM), an antiemetic drug, has been used in treatment of adults and children. It has low aqueous solubility and hence low bioavailability. In present study, an attempt has been made to enhance the solubility of DOM by inclusion complexation with Hydroxypropyl-β-Cyclodextrin (HP-β-CD) using kneading technique and formulation of fast disintegrating tablets by using Sodium Starch Glycolate as superdisintegrant. Solubility analysis of DOM in different concentrations of HP-β-CD was carried out. Design of experiment (DOE) is done by using MINITAB 15.1 software to find out the variable for dissolution and disintegration time. HP-β-CD and SSG were identified as the variable for disintegration time and dissolution. For optimization of the concentration of HP-β-CD and SSG, two factors at two levels design through central composite design (CCD) were used which gave 13 formulations. All formulations are evaluated for characteristics such as weight variation, hardness, friability, disintegration time and dissolution of drug. Solubility of DOM increases linearly with increase in concentration of HP-β-CD. The optimum concentration of HP-β-CD is found to be in 1:2 molar ratios and SSG of 7%. The In-Vitro dissolution studies of optimized formulation and market sample were carried out in USP type II apparatus at different time intervals of 5, 10, 15 and 30 minutes at 50 rpm in 0.1 N HCl. The dissolution and disintegration time of optimized formulation is found better than market sample.

Determination of Chlorobenzene by Hydroxypropyl-β- Cyclodextrin Sensitized Fluorescence Quenching Method with Neutral Red as a Fluorescence Probe

The fluorescence quenching of inclusion complex of neutral red （NR） and hydroxypropyl-β-cyclodextrin （HP-β-CD） carried by chlorobenzene was investigated. The fluorescence intensity of NR increased due to the formed inclusion complex of HP-β-CD and NR. But the fluorescence intensity of NR-HP-β-CD diminished when chlorobenzene was added, and there was a linear relationship between the fluorescence quenching value of the system （△IF = IF, NR-HP-β-CD - IF, CB-NB-NR-HP-β-CD） and the concentration of chlorobenzene. Based on this, a novel fluorescence quenching method for the determination of chlorobenzene with NR as a fluorescence probe has been developed. Under the optimal conditions, the linear range of calibration curve for the determination of chlorobenzene was 5.0 × 10^-8 - 8.0 × 10^-6 mol/L and the detection limit was 1.0 × 10^-8 mol/L. It has been applied to determination ofchlorobenzene in synthetic waste water samples with satisfactory results.

Lyophilization Process of Hydroxypropyl Tetrahydropyrantriol Liposomes

[Objectives]To enhance the skin permeability of hydroxypropyl tetrahydropyrantriol and provide a reference for the subsequent prevention or treatment of skin aging.[Methods]The lyophilization process of hydroxypropyl tetrahydropyrantriol liposomes was investigated using a single factor method,and a quality evaluation system was established based on the appearance,particle size,PDI,and re-dispersibility of the lyophilized samples.[Results]The lyophilization process of hydroxypropyl tetrahydropyrantriol liposomes was determined by single factor experiments.The pre-freezing period was 16 h at-80℃,the total drying time was 36 h,and the addition of 10%mannitol-sucrose was used as the lyoprotectant.[Conclusions]The product prepared by the lyophilization method exhibits a fluffy and full appearance,with minimal shrinkage and collapse.The volume remains consistent before and after lyophilization,and the re-dispersibility is satisfactory.The re-dissolution process is rapid,and the particle size and polydispersity index(PDI)remain largely unchanged before and after lyophilization.

Adsorption of Phenanthrene in Soil to Biochar Modified by β-Cyclodextrin

In this study, the adsorption effect of β-cyclodextrin modified biochar (BC) on phenanthrene (PHE) in contaminated soil was investigated, aiming to provide an efficient and environmentally friendly remediation strategy for Polycyclic Aromatic Hydrocarbons (PAHs) contaminated soil. Through kinetic and isotherm analysis, β-CDBC-CA showed excellent phenanthrene adsorption performance, and the adsorption effect increased with the increase of time and was affected by temperature. The results show that β-CDBC-CA can not only effectively adsorb phenanthrene in soil, but also serve as a surfactant to help desorption phenanthrene adsorbed by soil organic matter and improve the efficiency of microbial degradation. The experimental data showed that the Elovich model could describe the adsorption behavior of β-CDBC-CA on phenanthrene well, while Langmuir and Freundlich models performed better in fitting parameters, revealing the adsorption mechanism of phenanthrene in contaminated soil by β-cyclodextrin-modified biochar. In addition, temperature has a significant effect on the adsorption capacity of β-CDBC-CA, and its application in soil remediation can be optimized by adjusting temperature. This study not only provides new materials and technical means for soil remediation but also provides important data support for an in-depth understanding of the environmental behavior of PAHs. By citing relevant research results, this study further improves the control and understanding of environmental risks of PAHs, which is of great significance for the protection of ecological environment and human health.

Synthesis and Characterization of β-Cyclodextrin Modified Biochar Environmental Remediation Materials

In this paper, biochar (BC) was used as raw material, activated by deionizing aqueous solution, NaCl solution, CA solution and HCl solution respectively. Epichlorohydrin (EPI) was used as crosslinking agent, and β-cyclodextrin (β-CD) was used to modify biochar (BC). The prepared modified biochar materials were labeled with β-CDBC, β-CDBC-Na, β-CDBC-CA and β-CDBC-H, respectively. The infrared spectrum, X-ray diffractometer, scanning electron microscope and specific surface area of the four modified materials were tested. The results showed that the C-O stretching vibration peak at 1020 cm−1 of the modified materials was slightly offset compared with that of biochar. The characteristic absorption peaks of XRD pattern decrease obviously at 2θ = 26.7˚ and 29.5˚. It can be obviously observed on the electron microscope image that the surface is loaded or formed clathrates, and BET data and graphs also show that the specific surface area of the modified biochar is larger. Therefore, β-cyclodextrin successfully modified biochar and formed clathrates on the surface of biochar or was loaded in the pore structure of biochar, especially β-CDBC-CA achieved better modification effect. Because biochar and β-cyclodextrin raw materials are cheap, easy to prepare and green, and less prone to secondary pollution, it has a good advantage in environmental governance.

Separation Properties of a New Polysiloxane-Anchored β-Cyclodextrin Derivative as Gas Chromatography Stationary Phase

A new capillary gas chromatography stationary phase, monokis (2,6 di O benzyl 3 O propyl (3’)) hexakis(2,6 di O benzyl 3 O methyl) β CD bonded polysiloxane, was synthesized. It exhibited separation abilities to disubstituted benzene isomers and some chiral solutes. It was also found that the polarity of CD derivatives can be lowered both by chemically bonding it to polysiloxane and by diluting it in polysiloxane. The separation abilities of the polysiloxane anchored CDs (SP CD) are higher than that of the unbonded CDs (S CD) and the diluted S CD at lower column temperature. Hydrosilylation reaction is one of the best methods to lower the operating temperature of CDs.

VOLTAMMETRIC BEHAVIOR OF ASCORBIC ACID AT α-CYCLODEXTRIN INCORPORATED CARBON NANOTUBES-COATED ELECTRODE

制备了α -环糊精掺杂纳米碳管涂层电极并应用于抗坏血酸的电催化氧化 ,结果表明 ,氧化电位降低了 2 80mV ,电流响应明显增加。我们首次结合两种物质的特性 :纳米碳管的导电性及催化性能、α -环糊精的分子认知能力 ,对电极表面进行修饰。实验了抗坏血酸与α -环糊精超分子络合物的特性。差示脉冲技术用于定量分析抗坏血酸 ,线性范围为 2 .5× 10 -6～ 1.0× 10

Synthesis and Characterization of Peralkylated β-Cyclodextrins Used as Gas Chromatographic Stationary Phasest

Six peralkylated β- cyclodec\xtrins used as capillary gas chromatographic stationary phases were prepared and characterized by differential by differential scannning calorimetry(DSC) and pyrolysis gas chromatography (PyGC). The DSC profiles illustrated that the peralkylated β-cyclodextrins synthesized possess the supercoooled state and the glass state below their melting point The PYGC results showed that the long-chain alkylated β-cyclodextrins are more thermostable than the short-chain. one All ofthese peralkylated β-cyclodextrins are suitable for use as capillary column gas chromatographic stationary phases,which can easily be coatal on the fused silica capilary columns and have nice chromatographic retention behaviour. For example, the capillary colunns coated with these materials can excellently separate three methylphenol isomers and six dimehylphenol isomers.

Investigation on Non-covalent Complexes of Cyclodextrins with Li＋ in Gas Phase by Mass Spectrometry

To investigate the non-covalent interaction between cyclodextrins （CD） and lithium ion, a stoichiometry of α-CD, β-CD, heptakis（2,6-di-O-methyl）-β-CD （DM-β-CD）, or heptakis（2,3,6-tri-O-methyl）-β-CD （TM-β-CD） was mixed with lithium salt, respectively, and then incubated at room temperature for 10 min to reach the equilibrium. In posi- tive mode, the electrospray ionization mass spectrometry （ESI-MS） results demonstrated that lithium ion can conjugate to α-, β-, DM-β- or TM-β-CD and form 1：1 stoichiometric non-covalent complexes. The binding of the complexes was further confirmed by collision- induced dissociation. The dissociation constants Kdl of four complexes （Li＋α-CD, Li＋β- CD, Li＋DM-β-CD, and Li＋TM-β-CD） were determined by mass spectrometric titration. The results showed Kdl were 18.7, 26.7, 33.6, 30.5 μmol/L for the complexes of Li＋ with α-CD, β-CD, DM-β-CD, and TM-β-CD, respectively. Kdl for the Li＋ complexes of/3-CD is smaller than that of DM-β-CD due to its steric effect of the partial substituted -CH3. The Kdl for the Li＋ complexes of DM-β-CD is nearly in agreement with that of TM-β-CD, indicating Li＋ is more likely to locate in the small rim of DM-β-CD＇s hydrophobic cavity. The DFT results showed through electrostatic interaction, one Li＋ can strongly conjugate to four neighboring oxygen atoms. For the （α-CD＋Li）＋ complex, one Li＋ may also situate the small rim of α-CD＇s hydrophobic cavity to form a non-specific host-guest complex.

APM3 Molecular Orbital Study on the Conformational Equilibrium of Cyclohexane upon α-Cyclodextrin Inclusion Complexation

用PM3分子轨道方法研究了α -环糊精的包合作用对环己烷构象平衡的影响。发现α -环糊精的包合作用可以改变环己烷的构象平衡。计算结果表明 ,虽然环己烷的椅式构象比船式构象稳定 1 8.5kJ·mol-1,但在α-环糊精的包合物中 ,船式环己烷包合物比椅式环己烷包合物稳定4.4kJ·mol-1。因此 ,超分子体系中客体分子的构象平衡不能简单地从其游离态的构象平衡外推得到 。

Effects of β-cyclodextrins on the enzymatical hydrolysis of chiral dichlorprop methyl ester

The effect of β-cyclodextrins(β-CDs) on the enzymatical hydrolysis of chiral dichlorprop methyl ester (DCPPM) was studied. Four kinds of β-cyclodextrins(β-cyclodextrin, Partly methylated-CD(PM-β-CD), hydroxypropyl-cyclodextrin(HP-β-CD) and carboxymethyl-cyclodextrin(CM-β-CD)) were used. Compared with 100% DCPPM in the absence of β-cyclodextrins, the activity of lipase decreased with the increase of β-cyclodextrin and PM-β-cyclodextrin. However, CM-β-cyclodextrin stimulated the lipase activity. The inhibition effect of β-cyclodextrin and PM-β-cyclodextrin on the hydrolysis of DCPPM is affected by many factors other than degree of the methylation blocking the active site of lipase. UV-Vis and Fourier transform infrared(FTIR) spectroscopy studies of the complexation of aqueous DCPPM with β-CDs provide fresh insight into the molecular structure of the complex and explain the effects of β-CDs on enzymatical hydrolysis of chiral DCPPM. Data showed that inclusion complexes had formed by complexation of the CM-β-CD with DCPPM and the solubility of DCPPM was increased in water, which leaded to the increased lipase activity.