Inclusion of acaricides by complexation withβ-cyclodextrin

Many synthetic pesticides (herbicides, insecticides, fungicides etc.) can be complexed with cyclodextrins. The inclusion complexes of acaricides such as Fenson, Chlorfenson and Genite were prepared. The formation of inclusion complexes was established by UV and X-ray diffraction techniques. The host-to-guest ratio was determined by UV spectral and GLC methods.This paper is dedicated to Professor A.B. Kulkarni on his 75th birthday.     

Investigation of monoterpenes complexation with hydroxypropyl-β-cyclodextrin

In this study, we investigated the inclusion complexation of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and eight monoterpenes (eucalyptol, geraniol, limonene, linalool, α-pinene, β-pinene, pulegone, and thymol) in aqueous solution and solid state. The formation constants (K _f) of inclusion complexes were determined using fluorescence spectroscopy and static headspace gas chromatography. The results indicated the formation of 1:1 inclusion complexes between HP-β-CD and all studied guests. A linear relationship was found between K _f values and the hydrophobic character of the monoterpenes expressed as logP. Solid complexes were prepared by the freeze-drying method in a 1:1 (HP-β-CD:monoterpene) molar ratio. Physicochemical characterization of solid inclusion complexes was carried out using Fourier transform infrared spectroscopy and differential scanning calorimetry. Finally, the encapsulation efficiency (EE%) of HP-β-CD was determined using HPLC analysis. Noticeable difference in the EE% was observed between monoterpene hydrocarbons and oxygenated monoterpenes. These results suggested that complexation with HP-β-CD could be a promising strategy to enlarge the application of monoterpenes in cosmetic, pharmaceutical and food industries.     

Studies on methylatedβ-cyclodextrins and C60 inclusion complexes

Solid, water-soluble inclusion complexes: DMCD/C₆₀ (1:1) and DMCD/C₆₀ (2:1) can be obtained by kneading. Their formation has been confirmed by UV-vis spectroscopy, X-ray diffraction and DSC studies. UV-vis studies also reveal the transformation between the two complexes in aqueous solution. TMCD has also been studied as the host of an inclusion complex with C₆₀.     

The effect of phosphate buffer solutions on uniconazole complexation with hydroxypropyl-β-cyclodextrin and methyl-β-cyclodextrin

The inclusion complexes of uniconazole [(E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-lyl)-1-penten-3-ol, UCZ] with two cyclodextrin derivatives, hydroxypropyl-β-cyclodextrin (HP-β-CD) and methylated-β-cyclodextrin (Me-β-CD), were prepared and characterized by ¹H NMR and FT-IR. The phase solubility of UCZ and HP-β-CD, UCZ and Me-β-CD, which displays the ability of CDs complexation and solubilization, was studied in aqueous solutions and phosphate buffer solutions (PBS) with different property pH values (6.2, 7.2, 8.0). The solubility results indicated that the pH of PBS showed more enhancement on the interaction of HP-β-CD and UCZ than Me-β-CD with the increasing pH value, and the optimal pH value for complexation of UCZ and HP-β-CD, UCZ and Me-β-CD was at 8.0 and at 7.2, respectively. These were also determined by UCZ release behavior and dissolution studies of the complexes in solid state.     

Molecular inclusion complexation of tolbutamide with permethyl-β-cyclodextrin

The formation of a stable inclusion complex between tolbutamide and permethyl- cyclodextrin was systematically studied. It shows that permethyl--CD forms a 1 : 1 complex with tolbutamide. Its molecular structure was elucidated by physicochemical methods including IR and high field NMR analysis. The influence of pennethyl--cyclodextrin on the hypoglycemic effect of tolbutamide was evaluated by measuring the blood glucose level. The reduction in plasma glucose was significantly greater when the rabbits were treated with the complex than with tolbutamide alone. The enhancement of the bioavailability of tolbutamide by permethyl--cyclodextrin is likely attributed to the molecular inclusion effect.     

Theoretical am1 studies of inclusion complexes of α- and β-cyclodextrins with methylated benzoic acids and phenol,and γ-cyclodextrin with buckminsterfullerene

Semiempirical AM1 calculations have been performed on the inclusion complexes of - and -cyclodextrin with benzoic acid and phenol and -cyclodextrin with methylated benzoic acids in the head first and tail first positions. The results show that -cyclodextrin complexes with phenol and benzoic acid guests in the head first position are more stable than in the tail first position, while -cyclodextrin complexes with the same guests prefer the tail first position. The preferred orientation for -cyclodextrin with methylated benzoic acids is determined by the position of the methyl substituent(s). In general, para-methyl benzoic acid derivatives prefer the tail first position. -cyclodextrin forms a slightly unstable 1:1 complex with C₆₀ (3.4 kcal/mol), but two -cyclodextrins provide enough stabilization by about 10 kcal/mol to cage-in the C₆₀.     

Electrochemical study of indapamide and its complexation with ��-cyclodextrin

Electrochemical oxidation of indapamide has been investigated at glassy carbon electrode using cyclic and differential pulse voltammetry (DPV). Indapamide exhibited two well resolved signals which attributed to the oxidation of indoline ring and benzamide moiety in phosphate buffers in the pH range of 2.7?C10.1. The oxidation processes have been shown to be irreversible and diffusion controlled. The formation of an inclusion complex of indapamide with ??-cyclodextrin (??-CD) has been investigated by cyclic, differential pulse voltammetry as well as UV?CVis spectrophotometry. The stability constant of the complex was determined to be 6199 and 2717 M^?1 using differential pulse voltammetry and UV?CVis spectrophotometry, respectively.     

Electron transfer reactions associated with ethyl viologen-β-cyclodextrin complexation: equilibrium and kinetic aspects

Formation of the complex of ethyl viologen in its cationic (Ev^+?) and neutral (Ev^°) forms with β-cyclodextrin (β-CD) was investigated by means of voltammetric technique in buffer solution of pH 7.00. The number of βCD (n or m) per viologen species (Ev^+?) or (Ev^°), bonding equilibrium constants as well as bonding rate constants was calculated. The calculated values of $K_{\text{eq}}^{(1)}$ and $K_{\text{eq}}^{ ( 2)}$ (pertaining to the bonding of Ev^+? and Ev^° with βCD) are 13.6 M^–n and 2.1 × 10³ M^?m , respectively, whereas the calculated values of n and m are 0.54 and 1.25, respectively. The bimolecular rate constant for the Ev^°?βCD inclusion complex formation is 3.03 × 10³ M^?1s^?1. These results are supported by the simulation of the experimental cyclic voltammograms. This study also highlights the significance of the proposed electrochemical method as compared to earlier studies on viologen-Cyclodextrin systems.     

Binding of vitamin A byβ-cyclodextrin and heptakis(2,6-O-dimethyl)-β-cyclodextrin

Inclusion complexation of all-trans-retinol, retinal and retinoic acid with -cyclodextrin (-CD) and heptakis(2,6-O-dimethyl)--cyclodextrin (DM--CD) were investigated by means of UV-vis spectroscopy. The association constants (K _a) obtained for vitamin A with DM--CD is greater than with -CD. On the other hand, for the same host compoundK _a values of retinol, retinal and retinoic acid are very close to each other.     

Inclusion complexation of 4,4′-dihydroxybenzophenone and 4-hydroxybenzophenone with α- and β-cyclodextrins

The inclusion complexation behaviours of 4,4′-dihydroxybenzophenone (DHBP) and 4-hydroxybenzophenone (HBP) with α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) were investigated using UV–visible fluorescence, time-resolved fluorescence, molecular modelling, scanning electron microscopy (SEM), FTIR, differential scanning calorimeter, X-ray diffraction, ¹H NMR and molecular modelling techniques. In both molecules, biexponential decay was observed in water, whereas triexponential decay was observed in the CD medium. The DSC thermogram of the DHBP/α-CD and DHBP/β-CD inclusion complex nanomaterials shows the endothermic peak at 60.8, 101.9, 119.6 and 112.8°C. The upfield chemical shift observed for HBP protons reveal that the phenyl ring (without hydroxyl substitution) entered the CD cavity and the hydroxyl group of HBP is exposed outside the CD cavity. The SEM image of DHBP appears as needle-shaped crystals on the micrometre scale, whereas the irregular bar shape was observed for HBP. Transmission electron microscopy images show that both guest molecules formed nano vesicles with α-CD and formed nano rods with β-CD.     

Release control of fragrances by complexation with β-cyclodextrin and its derivatives

The release control of fragrances, benzyl acetate (BA), citral (CR), linalool (LL), citronellol (CL) and linalyl acetate (LA), was conducted using β-cyclodextrin (β-CyD), 2-hydroxypropyl-β-CyD (HP-β-CyD) and 2,6-di-O-methyl β-CyD (DM-β-CyD). The release rate of the fragrances from 30% ethanol/water solution was significantly suppressed by the complexation with these CyDs, and the suppressing effect increased in the order of β-CyD?<?HP-β-CyD?<?DM-β-CyD. The concentration-dependent change of the release rate was quantitatively analyzed to obtain the stability constant (Kc) of the fragrance-CyD complexes. These Kc values were in good agreement with those determined by the solubility method. The results suggest that the release of fragrances can be prolonged by the complexation with β-CyDs and their effects can be controlled by choosing appropriate CyD derivatives with higher Kc values and by setting proper concentrations of the host molecules.     

On the complexation of Trolox with methyl-β-cyclodextrin: characterization, molecular modelling and photostabilizing properties

Exposure to UV radiations could reduce the efficiency of some antioxidants like Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a water-soluble vitamin E analogue largely employed in cosmetic products. Accordingly, in this paper we examined the possibility of increasing the stability of Trolox towards UVB irradiation by its complexation with methyl-β-cyclodextrin. Formation of the inclusion complex was confirmed by solubility diagrams, differential scanning calorimetry (DSC), and diffusion study through hydrophilic membrane. The stability constants and docking results suggested that the complexation phenomenon was related to the pH of the medium. The photodegradation studies were carried out in different topical formulations (gel, O/W emulsion, and W/O/W emulsion) containing Trolox free or complexed with methyl-β-cyclodextrin. Results showed that in all the cases Trolox degraded following pseudo-zero order kinetics. Moreover, the host molecule increased Trolox photostability also in the presence of TiO₂, a physical sunscreen well-known as photocatalyzer.     

Thermodynamics of complexation of tauro- and glyco-conjugated bile salts with two modified ��-cyclodextrins

The interaction between two modified ??-cyclodextrins and bile salts, common for rat, dog and man, was studied using isothermal titration calorimetry. The structural differences in the interaction were investigated by ¹³C NMR. The two modified ??-cyclodextrins were chosen because of their frequent use as oral excipients in drug formulation and in marketed products. All the investigated bile salts had an affinity for the ??-cyclodextrins, although there were large variations in the stability constants. The variations in the enthalpic and entropic contributions to the overall Gibbs free energy revealed differences in the binding mode to the investigated bile salts, i.e. the bile salts with a hydroxyl group at C12 interacted differently than bile salts without this hydroxyl group. These observations were supported by ¹³C NMR, which suggested binding to the D-ring of the steroid structure for bile salts with a hydroxyl group at C12 and to the C-ring for the bile salts without this hydroxyl group. The type of substitution of ??-cyclodextrin had significant effects on the thermodynamics of the interaction where especially the entropic changed were affected.     

Liposome solubilization induced by complexation with dimeric β-cyclodextrin

Dimeric β-cyclodextrins (β-CD) were prepared from the reaction of native β-CD with epichlorohydrin under basic conditions, and the effects on the diacetylene (DA) and polydiacetylene (PDA) liposomes have been investigated. Vesicular DA was solubilized in the presence of dimeric β-CD with the consequent inhibition of polymerization. The result is attributed to the formation of a complex between dimeric β-CD and DA liposomes, and it is clearly differentiated from that of monomeric β-CD. Furthermore, the ordered supramolecular structure of PDA was perturbed by the dimeric β-CD, which was detected from the visible color change. Finally, the morphological characteristics and size of PDA in the absence and presence of dimeric β-CD were examined using transmission electron microscopy and dynamic light scattering The results show fused structure of size more than 200 nm along with the deformation of the vesicles, and they represent a novel phenomenon of liposome structure induced by complexation with dimeric β-CD. The evaluated physicochemical characteristics can be applied to the development of carbohydrate-based detergents.     

Enhanced water-solubility of albendazole by hydroxypropyl-β-cyclodextrin complexation

The inclusion complexation of methyl (5-(propylthio)-1H-benzimidazol-2-yl) carbamate, albendazole (ABZ) with 2-hydroxypropyl--cyclodextrin (HPCD) in water was investigated with a view to improving the low aqueous solubility of the drug. The combination of albendazole and HPCD in a molar ratio of 1/10 resulted in a significant increase in the aqeous solublity of the drug, up to 3500 times. Albendazole/HPCD complexes could be recommended as a parenterally administered formulation because of its good solubility properties and the safety of the cyclodextrin used.     

Study of complexation of gliclazide with β-cyclodextrin in solution by nmr techniques

The study of complexation between GL and -CD in liquid medium has been carried out by phase-solubility,¹H and¹³C NMR studies. A formation complex is observed from the phase solubility diagram, being the average association constant of 1094 M^–1, The NMR studies revealed the preferent complexation of the aliphatic moiety of GL. The aromatic moiety is also entrapped, but in minor extent, by the CD molecules.     

Inclusion complexes of sulfanilamide with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin

Sulfanilamide belongs to the group of drugs that have a bacteriostatic effect on different pathogenic microorganisms. This activity originates from the competitive antagonism with p-aminobenzoic acid, which is an integral part of folic acid. The safe use of sulfanilamide is limited due to poor solubility in the aqueous medium. Therefore, the aim of this paper is the synthesis of sulfanilamide, as well as preparing and structural characterization of its inclusion complexes with cyclodextrins. The crude sulfanilamide was obtained in the synthesis between acetanilide and chlorosulfonic acid according to the standard procedure. The synthesized sulfanilamide was recrystallized from water in order to obtain the satisfactory purity of the substance. Sufanilamide was complexed with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin by the co-precipitation method. A molecular encapsulation of sulfanilamide was confirmed by using FTIR, ¹H-NMR, XRD and DSC methods. Phase-solubility techniques were used to assess the formation of the inclusion complex between sulfanilamide and cyclodextrins. The photostability of sulfanilamide and its inclusion complexes was estimated by UVB irradiation in a photochemical reactor by applying the UV–Vis method. Based on the UV–Vis analysis, sulfanilamide:2-hydroxypropyl-β-cyclodextrin complex was presented as more photostable than sulfanilamide:β-cyclodextrin complex and sulfanilamide. The obtained results enable the potential use of these inclusion complexes for the preparation of oral formulations due to the enhanced solubility of sulfanilamide.     

Inclusion complexes of 5-flucytosine with β-cyclodextrin and hydroxypropyl-β-cyclodextrin: characterization in aqueous solution and in solid state

Complexation between 5-flucytosine (5-FC), a cytosine analogue with in vitro antifungal and antiyeast activity, and β-cyclodextrins (β-cyclodextrin and hydroxypropyl-β-cyclodextrin) was studied in solution and in solid states. Complexation in solution was evaluated using solubility studies, UV–vis and ¹H-NMR. In the solid state, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), FT-IR and X-ray diffraction studies were used. UV–vis, FT-IR and ¹H-NMR spectroscopy studies showed that the complex formed occurs by complexation of piridinique base analogue into inner cavity. DSC studies showed the existence of a complex of 5-FC with β-CDs. X-ray studies confirmed the DSC results of the complex existence. Solubility studies showed that the complexed drug is forty times more soluble than free 5-FC, indicating the obtained systems as future, promising drug carriers.