Preparation and characterization of Mentha x villosa Hudson oil–β-cyclodextrin complex

Inclusion complex between the essential oil of Mentha x villosa Hudson and β-cyclodextrin, with a 1:9 mass/mass oil–β-cyclodextrin ratio was prepared by co-precipitation and kneading methods in a hydroethanolic medium. The GC/MS analysis showed a total volatile content of 99.5% in the Mentha x villosa oil. The characterization of the complex involved the analysis of the original essential oil, the surface and the total extracted oils. Among 28 detected compounds in the original essential oil, 13 are monoterpenes and 10 sesquiterpenes, furthermore, piperitenone-oxide is the major component (35.4%). 12 compounds were totally and 11 partially complexed, 3 have been adsorbed only on the surface of the β-CD and 2 have not been detected neither in the surface oil nor in the complexed oil. A 13.6% encapsulation efficiency was observed, while the total oil and volatiles retention was 15 and 77%, respectively. Non-parametric statistic analysis of the data showed that the profile of the volatiles were not significantly different comparing the original oil and the complexed oil (p>0.04). The results of thermogravimetry-mass spectrometry and XRD analysis have proven the inclusion complex formation between the essential oil and cyclodextrin.     

Application of combined thermoanalytical techniques in the investigation of cyclodextrin inclusion complexes

Citronellol and citronellyl acetate have been entrapped with α-, β- and γ-cyclodextrin (CD). Evolved gas detection and TG-MS coupling was applied to prove the actual inclusion complex formation between monoterpens and CDs. The terpene content was determined by UV-VIS specrophotometry and RP-HPLC and the effect of storage time on the terpene content was also investigated. The α- and γ-cyclodextrin inclusion complexes showed higher thermal stabilities vs. dynamic heating compared to the β-CD complexes. On the contray, the retention of guest using β-cyclodextrin even after 10 years of storage was much more pronounced. Experimental data other than 1:1 complex compositions are assumed. Molecular modeling experiments also suggested multiple complex compositions.     

Solid-state characterization and dissolution properties of ezetimibe–cyclodextrins inclusion complexes

The objectives of this research were to prepare and characterize inclusion complex of Ezetimibe (EZE) with cyclodextrins (β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HPβ-CD)) and to study the effect of complexation on the dissolution rate of EZE, a water insoluble drug. Phase solubility curve was classified as A _P -type for both cyclodextrins, indicating the 2:1 stoichiometric ratio for β-CD–EZE and HPβ-CD – EZE inclusion complexes. The inclusion complexes in the molar ratio of 2:1 (β-CD–EZE and HPβ-CD–EZE) were prepared by various methods such as kneading, coevaporation and physical mixing. The molecular behaviors of drug in all samples were characterized by fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies. The results of these studies indicated that complex prepared by kneading and coevaporation methods showed inclusion of the EZE molecule into the cyclodextrins cavities. The highest improvement in in-vitro dissolution profiles was observed in complex prepared with hydroxypropyl-β-cyclodextrin using co-evaporation method. Mean dissolution time and similarity factor indicated significant difference between the release profiles of EZE from complexes and physical mixtures and from pure EZE.     

Study on the Association Phenomenon of Cyclodextrin to Porphyrin J-aggregates by NMR Spectroscopy

The nuclear magnetic resonance (NMR) spectroscopy demonstrated that the inclusion complexes of meso-tetrakis- (p-sulfonatophenyl) porphyrin (TPPS) with β-, Hydroxypropyl-β- and Methyl-β-cyclodextrin (β-, HP-β- and Me-β-CD) are formed, which resulted in the dissociation of TPPS J-aggregates efficiently under certain acidity. There are no significant differences in binding affinities and basic complexation mechanisms between TPPS and β-cyclodextrin (β-CD) or hydroxypropyl-β-cyclodextrin (HP-β-CD), i.e. porphyrin is included through the wide side of the cavity of β-CD or HP-β-CD. Alternatively, porphyrin is included through the narrow side of the Me-β-CD cavity.     

Investigation of the Hydrocortisone-<Emphasis Type="Italic">β</Emphasis>-Cyclodextrin Complex by Phase Solubility Method: Some Theoretical and Practical Considerations

Phase solubility diagrams (PSDs) and molecular mechanical (MM) modeling were used to study the complexation of hydrocortisone (HCor) with β-cyclodextrin (β-CD). The phase solubility profile of HCor with β-CD was classified as the B_s-type. PSDs revealed a six-fold increase in HCor water solubility upon addition of 7 mmol⋅dm⁻³ β-CD concentration (solubility in 7 mmol⋅dm⁻³ of β-CD/solubility in water). The thermodynamic study shows the complexation process is exothermic, with a ΔH value of −5.28 kJ⋅mol⁻¹. MM calculations were used to predict the optimal stoichiometry of the complex formed as well as the possible orientations of HCor inside the β-CD cavity. The complexes prepared were analyzed through chemical analysis, which provides evidence for the 1:1 complexation of HCor/β-CD. Electronic Supplementary Material The online version of this article () contains supplementary material, which is available to authorized users.     

Thermal analysis and gas chromatography coupled mass spectrometry analyses of hydroxypropyl-β-cyclodextrin inclusion complex containing Lippia gracilis essential oil

Inclusion complexation with cyclodextrins is an effective way to improve stability and turn liquid materials into re-dispersible and easy-to-handle powders. In the present work, the complexation of L. gracilis essential oil, already recognized as a potent larvicide material, with hydroxylpropyl-β-cyclodextrin was performed using slurry and paste procedures and the complexes obtained were evaluated. The gas chromatography coupled to mass spectrometry (GC/MS) analysis showed a total volatile content of 99.24% in the L. gracilis oil. The characterization of the complex involved the analysis of the original essential oil, the surface, and the total extracted oils. The major components in L. gracilis essential oil were identified as carvacrol (23.52%), p-cymene (15.82%), γ-terpinene (14.17%), and thymol (7.27%). GC/MS results showed significant differences between the original oil, the slurry, and paste complexation. Thermal characterization indicates the occurrence of complexation, mainly in paste complexes, which presents a TG–DTA peak at 230–275 °C, probably related to oil loss.     

Interaction of Valdecoxib with β-cyclodextrin: Experimental and Molecular Modeling Studies

This study aimed to investigate the effect of β-cyclodextrin on aqueous solubility and dissolution rate of valdecoxib and also to get an insight of molecular interactions involved in formation of valdecoxib‐β-cyclodextrin inclusion complex. Phase solubility analysis indicated complex with possible stoichiometry of 1:1 and a stability constant of 234.01 M⁻¹. Thermodynamic studies in water indicated exothermic nature of inclusion complexation.␣Valdecoxib‐β-cyclodextrin complexes (1:1 M) were prepared by kneading method, solution method and␣freeze–drying method. The complex was characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (P-XRD), Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance␣(¹H-NMR) spectroscopy. Molecular modeling was used to help establish the mode of interaction of β-cyclodextrin with valdecoxib. ¹H-NMR analysis suggested that the unsubstituted phenyl ring of valdecoxib display favorable interaction with the hydrophobic cavity of β-cyclodextrin, which was confirmed by molecular dynamic simulations. An inclusion complex model has been established for explaining the observed enhancement of solubility of valdecoxib in water by β-cyclodextrin. Dissolution studies in water showed that the valdecoxib in freeze-dried complex dissolved much faster than the uncomplexed drug and physical mixture. This improvement in dissolution rate is attributed to the increased solubility and wettability due to encapsulation along with decreased crystallanity caused by complex formation, which is evident by DSC and P-XRD studies.     

Encapsulation of Satureja montana essential oil in β-cyclodextrin

Inclusion complexes between the Satureja montana essential oil and β-cyclodextrin were prepared by co-precipitation method with the four oil to β-cyclodextrin ratios of 5:95, 10:90, 15:85 and 20:80 (w/w) in order to determine the effect of the ratio on the inclusion efficiency of β-cyclodextrin for encapsulating oil volatiles. The characterization of the complex involved the analysis of the initial essential oil, the surface and the total extracted oils. The retention of essential oil volatiles reached a maximum of 93.15 % at the oil to β-cyclodextrin ratio of 15:85. Though, the maximum inclusion efficiency of β-cyclodextrin was achieved at the ratio of 20:80. The qualitative and quantitative composition of the volatiles in the total oil extracts was similar to the starting oil which is confirmed the high inhibition zone as antifungal and high antioxidant properties after encapsulation to β-cyclodextrin. This justifies the use of β-cyclodextrin as complexion agent for S. montana essential oil in the food and pharmaceutical industries.     

A new sprout inhibitor of potato tuber based on carvone/β-cyclodextrin inclusion compound

A monoterpene, D-carvone or (4S)-(+)-carvone, present in the essential oil of caraway seeds (Carum carvi L.), acts as a sprouting inhibitor agent for potato tubers in storage. The aim of the present study was to investigate the possibility of using carvone/β-cyclodextrin inclusion compound as a sprout inhibitor agent for potato tubers. A Raman study of the interactions between β-cyclodextrin (β-CD) and included carvone molecule in solid state is also reported; the results confirm the synthesis of inclusion compound at pilot scale level.     

Thermoanalytical Studies on Complexes of Furosemide with β-Cyclodextrin Derivatives

Solid formulas obtained between furosemide and two β-cyclodextrin derivatives (HP-β-CD and RAMEB) were prepared by different methods and in various ratios (1:1 and 1:2). The inclusion complex formation between the drug and the β-CDs of 1:1 ratio was evaluated by mean of thermal analysis (DSC, TG and EGD). Supplementary techniques, such as X-ray diffraction, were also applied to interpret the results of the thermal study of physically mixed and kneaded products. Both studies demonstrated the formation of inclusion complexes in all samples except the physical mix samples; formation of true inclusion complexes was then possible only when the components were in melted form. The complexation increased the solubility and the rate of dissolution of the drug. RAMEB was found to be a better complexing agent than HP-β-CD; in both ratios it can be selected as a vehicle in furosemide tablet preparations. This revised version was published online in August 2006 with corrections to the Cover Date.     

Inclusion complexation of diclofenac with natural and modified cyclodextrins explored through phase solubility, 1H-NMR and molecular modeling studies

Guest–host interactions were examined for neutral diclofenac (Diclo) and Diclofenac sodium (Diclo sodium) with each of the cyclodextrin (CD) derivatives: α-CD, β-CD, γ-CD and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), all in 0.05 M aqueous phosphate buffer solution adjusted to 0.2 M ionic strength with NaCl at 20 °C, and with β-CD at different pHs and temperatures. The pH solubility profiles were measured to obtain the acid–base ionization constants (pK _as) for Diclo in the presence and absence of β-CD. Phase solubility diagrams (PSDs) were also measured and analyzed through rigorous procedures to obtain estimates of the complex formation constants for Diclo/CD and Diclo sodium/CD complexation in aqueous solutions. The results indicate that both Diclo and Diclo sodium form soluble 1:1 complexes with α-, β-, and HP-β-CD. In contrast, Diclo forms soluble 1:1 Diclo/γ-CD complexes, while Diclo sodium forms 1:1 and 2:1 Diclo/γ-CD, but the 1:1 complex saturates at 5.8 mM γ-CD with a solubility product constant (pK _sp = 5.5). Therefore, though overall complex stabilities were found to follow the decreasing order: γ-CD > HP-β-CD > β-CD > α-CD, some complex precipitation problems may be faced with aqueous formulations of Diclo sodium with γ-CD, where the overall concentration of the latter exceeds 5.8 mM γ-CD. Both ¹H-NMR spectroscopic and molecular mechanical modeling (MM⁺) studies of Diclo/β-CD indicate the possible formation of soluble isomeric 1:1 complexes in water.     

Enantioselective extraction of terbutaline enantiomers with <Emphasis Type="Italic">β</Emphasis>-cyclodextrin derivatives as hydrophilic selectors

Hydrophilic β-cyclodextrin (β-CD) and its derivatives are not soluble in organic liquids but they are highly soluble in water and can interact with enantiomers selectively to form diastereomeric complexes which enable their use as chiral selectors in chiral solvent extraction. In this paper, terbutaline enantiomers were extracted by hydrophilic β-CD derivatives in an aqueous/organic biphasic solvent system with racemic terbutaline in the organic phase and β-CD in the aqueous phase. Five β-CD derivatives, namely: methyl-β-cyclodextrin (Me-β-CD), hydroxyethyl-β-cyclodextrin (HE-β-CD), 2-hydroxyethyl-β-cyclodextrin (2-HE-β-CD), (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) and (4-sulfobutylether)-β-cyclodextrin (SBE-β-CD) were used as hydrophilic selectors, respectively. Process variables affecting extraction efficiency were investigated, namely influence of the type of organic solvents and β-CD derivatives, concentrations of selectors and terbutaline enantiomers, pH, and temperature. Experimental results show that the efficiency of extraction depends, often strongly, on process variables. All five β-CD derivatives studied preferentially extract the more biologically active (R)-terbutaline from the organic phase; HP-β-CD has the strongest recognition ability. The maximum enantioselectivity (α) of 1.42 was achieved under optimal conditions: pH 7.0 and temperature of 5°C. Utilization of the extraction method for separation of terbutaline enantiomers is expected to be cheap and easy to scale up to commercial scale.     

Composition of essential oils from <Emphasis Type="Italic">Salvia anatolica</Emphasis>, a new species endemic from Turkey

The component composition of essential oils produced by steam distillation from flower heads, leaves, and stems of Salvia anatolica (Lamiaceae), a recently described new species endemic from Turkey, was studied by GC/FID and GC/MS. A total of 127 volatile components representing 96% of the oil was identified in essential oil from flower heads and leaves. It was found that the principal oil components of flower heads and leaves were α-pinene (10.9%), β-pinene (6.7%), α-copaene (6.3%), heptacosane (6.2%), and hexadecanoic acid (5.0%). A total of 109 volatile compounds representing 87.9% of the oil was characterized in essential oil isolated from stems. The principal oil components of stems were identified as hexadecanoic acid (27.2%), tetradecanoic acid (15.2%), dodecanoic acid (5.5%), and α-copaene (5.0%). __________ Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 552–555, November–December, 2007.     

Study on Inclusion Complex Formation of <Emphasis Type="Italic">m</Emphasis>-Aminobenzoic Acid with Native and Substituted <Emphasis Type="Italic">β</Emphasis>-Cyclodextrins

The complex formation of native and substituted β-cyclodextrins with m-aminobenzoic acid in water was characterized by calorimetry, ¹H NMR and UV spectroscopic studies. These studies showed that β-, hydroxypropyl-β- and methyl-β-cyclodextrins form 1:1 inclusion complexes with m-aminobenzoic acid. The thermodynamic properties of complex formation (K,Δ_c G ^o,Δ_c H ^o,Δ_c S ^o) were calculated. It was found that the processes of complexation are mainly favorable entropically. Introduction of hydroxypropyl- and methyl-substituents into the β-CD molecule results in negligible enhancement of stability of the complexes formed. The structure of these substituents has no influence on the stability constant values. The insertion of the carboxylic group of m-aminobenzoic acid into the cyclodextrin cavity was confirmed by ¹H NMR data.     

Supramolecular complex formation of β-cyclodextrin polymer with substituted salicylic acid or 3-hydroxy-2-naphthoic acid and their electrorheological behaviors

According to the chemical design, electrorheological properties of supramolecular complex from β-cyclodextrin polymer (β -CDP) were discussed. Six supramolecular complexes of β-cyclodextrin polymer with substituted salicylic acid and 3-hydroxy-2-naphthoic acid were synthesized by the solid-phase self-assembly method, and their component and structure were characterized by NMR, FT-IR, UV-vis and the fluorescence analysis. Then the electrorheological properties of their suspensions in silicone oil were investigated under DC electric fields. It was found that the yield stresses of these supramolecular complex ER fluids were 7.3–9.8 kPa at 4 kV/mm in DC electric field, which were enhanced by 34%–72% compared with that of pure β-CDP. Among them, that of β-CDP/3-hydroxy-2-naphthoic acid ER fluid was the highest. It was also found that the ER effect of supramolecular complexes can be controlled by changing different guests. When the substituted group is at phenyl ring, ER behavior can be slightly adjusted by the different substituted groups, their number as well as their position at phenyl ring. This can be proved by the measurement of dielectric properties.     

11-Aminoundecanoic acid, Cyclodextrins (α, β) and Cucurbit[n]urils (n = 6, 7) as Building Blocks for Supramolecular Assemblies: A Thermodynamic Study

The formation of 1:1 complexes of α-, β-cyclodextrin, cucurbit[6]uril, and cucurbit[7]uril with 11-aminoundecanoic acid have been studied using calorimetric titrations. The influence of solvent composition (aqueous formic acid) upon the complex stability and the values of the reaction enthalpies and entropies has been studied in the case of α-cyclodextrin (α-CD). With increasing concentration of formic acid the values of the reaction enthalpy decrease and of the reaction entropy increase. All ligands examined form 1:1 complexes with 11-aminoundecanoic acid under the experimental conditions. However, it is also possible to study the formation of 2:1 complexes (ligand:aminocarboxylic acid ratio). Even the formation of mixed 1:1:1 complexes with two different ligands (ligand(1):ligand(2):aminocarboxylic acid ratio) can be measured.     

Host–Guest Interaction Study of Resveratrol With Natural and Modified Cyclodextrins

The aim of this work is to increase the stability and water solubility of resveratrol by complexation with different cyclodextrins. Furthermore, physical–chemical properties of each inclusion compound were investigated. Complexes of resveratrol with cyclodextrins both native (α, β, γ) and modified (2-hydroxypropyl-β-cyclodextrin, dimethyl-β-cyclodextrin) were obtained by using the suspension method. An inclusion complex with β-cyclodextrin was also prepared by using the microwave. Solid state characterization of the products was carried out using Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (DRX); solution studies were performed by UV–Vis spectrophotometry and ¹H-NMR spectroscopy. Phase solubility profiles with all cyclodextrins employed were classified as A_N type, indicating the formation of 1:1 stoichiometric inclusion complexes. Stability constants (K _c) from the phase solubility diagrams were calculated. Stability studies in the solid state and in solution were performed; the photodegradation by UV–Vis spectrophotometry was monitored. The isomerization rate trans to cis, in ethanol solution, decreased with inclusion. The dissolution studies revealed that resveratrol dissolution rate was improved by the formation of inclusion complexes.     

Chromatographic Retention of Epigallocatechin Gallate on Oligo-β-Cyclodextrin Coupled Sepharose Media Investigated Using NMR

The retention of epigallocatechin gallate (EGCG) on oligo-β-cyclodextrin (oligo-β-CD) bonded agarose chromatographic media was investigated. NMR spectroscopy in solution showed that the EGCG immerses into the β-CD cavity. The association constant calculated by NMR titration was used to estimate a retention factor which accurately reflected chromatographic behaviour. This correlation suggests that oligo-β-CD forms inclusion complexes with EGCG via the same mechanism as monomeric β-CD. Revised: 14 March and 25 April 2006     

Sulphamethizole-Cyclodextrin-Hydroxy Propylmethyl Cellulose Multicomponent Complexes

The effect of cyclodextrin complexation of sulphamethizole (SM) was studied. Two systems were prepared with two cyclodextrin derivatives, β-cyclodextrin (BCD) and hydroxypropyl-β-cyclodextrin (HPBCD): binary complexes and multicomponent systems (cyclodextrins and a hydroxylpropylmethyl cellulose K4M). Inclusion complexes were prepared by freeze-drying and characterized by thermal analysis (DSC) and X-ray diffractometry. The presence of the polymer in the solution increases the effect of cyclodextrins – specially BCD – on the solubility of SM. In solid state, binary inclusion complexes enhance the dissolution behaviour of SM but, from the multi-component complexes, the polymer controls the release of the drug. This revised version was published online in August 2006 with corrections to the Cover Date.     

Experimental Analysis of Complex Formation of Niflumic Acid with β-Cyclodextrins

Complex formation of niflumic acid with β-, hydroxypropyl-β- and methyl-β-cyclodextrins in aqueous solution (pH 7.4) were studied by calorimetry of solution, ¹H NMR spectroscopy and solubility method. The enhancement of niflumic acid solubility in the presence of hydroxypropyl-β-cyclodextrin was detected. This effect is explained on the basis of ¹H NMR data confirming the inclusion of hydrophobic trifluoromethylphenyl residue of niflumic acid molecule into the macrocyclic cavity. The thermodynamic parameters of 1:1 binding were derived from the data of␣calorimetry and solubility measurements. It was obtained, that complex formation of niflumic acid with β-cyclodextrin and both its derivatives is enthalpy driven. Substitutes surrounding the macrocyclic cavity slightly influence the thermodynamics of complex formation resulting in decrease of stability of the complexes formed.