Controlled drug release applications of the inclusion complex of peracetylated-β-cyclodextrin and water-soluble drugs formed in supercritical carbon dioxide

Supercritical carbon dioxide (scCO₂) processing was performed with mixtures of CO₂-soluble peracetylated-β-cyclodextrin (PAc-β-CD) heptakis(2,3,6-tri-O-acetyl)-β-cyclodextrin, and highly water-soluble drug molsidomine (MOL) to prepare inclusion complexes of MOL and PAc-β-CD. The MOL/PAc-β-CD inclusion complex was confirmed by differential scanning calorimetry, X-ray diffractometry, and ¹H NMR analyses. The complexes were further investigated for their potential use in controlled drug delivery applications. The in-vitro release of MOL from the peanut oil suspensions into aqueous phase was found to be significantly retarded by the complexation with PAc-β-CD, mainly due to the hydrophobic properties associated with the PAc-β-CD.     

环糊精衍生物对野黄芩素的增溶作用

采用相溶解度法考察了25℃时羟丙基-β-环糊精(HP-β-CD)、乙二胺-β-环糊精(en-β-CD)、二乙烯三胺-β-环糊精(dien-β-CD)对野黄芩素的增溶作用,得到野黄芩素在环糊精及其衍生物中的相溶解度曲线均为AL型,说明其与环糊精的包合比为1:1。结果表明3种环糊精主体化合物对野黄芩素的增溶作用大小为:en-β-CD>dien-β-CD>HP-β-CD。     

荧光光谱法研究山奈素与β-环糊精及其衍生物包合作用

采用荧光光谱法研究了β-环糊精(β-CD)、甲基-β-环糊精(M-β-CD)、羟丙基-β-环糊精(HP-β-CD)、磺丁基-β-环糊精(SBE-β-CD)与山奈素的包合特性.在固定山奈素浓度和改变环糊精及其衍生物浓度的情况下,山奈素荧光发射波长的变化以及荧光强度的增强表明了包合物的形成,用荧光双倒数法计算了环糊精及其衍...     

Inclusion Complexation of Phenoxyaliphatic Acid Derivatives of 3,3′-bis(indolyl)methanes with β-Cyclodextrin

The inclusion complexation behavior of phenoxyaliphatic acid derivatives of 3,3′-bis(indolyl)methane (BIMs 1–5) with β-cyclodextrin (β-CD) were investigated in both solution and solid state by means of UV-Visible, fluorescence spectroscopy, FT-IR and ¹H NMR techniques. The nature of the host–guest inclusion complex between BIMs and β-CD has been elucidated. The experimental results confirmed the existence of 1:1 inclusion complex of BIMs with β-CD. The binding constants describing the extent of formation of the complexes have been determined using Benesi-Hildebrand plots using UV-Vis and fluorescence spectroscopy. BIMs exhibited an affinity for β-CD. The spectral studies suggested the phenyl ring along with alkyl substitutions of BIMs is present inside of β-CD cavity.     

Encapsulation of nabumetone by means of -drug: (β-cyclodextrin)2:polyvinylpyrrolidone ternary complex formation

The aim of the present study was to investigate the effect of the presence of the water-soluble polymer polyvinylpyrrolidone (PVP) MW=24,000 g/mol, on the complexing of the anti-inflammatory drug nabumetone, with β-cyclodextrin (β-CD). The data show that the polymer interacts with the free nabumetone and with the nabumetone:β-CD inclusion complex, in both cases with a stoichiometry of 1:1. The interaction constants are 1.3×10⁴ M⁻¹ and 1.6×10⁴ M⁻¹, respectively.The presence of PVP, changes the drug:cyclodextrin interaction, a nabumetone:(β-CD)₂:PVP complex being formed.In addition, the presence of PVP, produces a strong increase in the global binding constant, β₂=(22.12±0.22)×10⁶ M⁻² at 1% PVP.In the ternary complex, the nabumetone is wrapped at both ends for the β-CD. In this complex the polymer seems to act as a bridge between both β-CD molecules that bind the nabumetone.     

Encapsulation of Labetalol, Pseudoephedrine in β-cyclodextrin Cavity: Spectral and Molecular Modeling Studies

The absorption and fluorescence spectra of labetalol and pseudoephedrine have been studied in different polarities of solvents and β-cyclodextrin (β-CD). The inclusion complexation with β-CD is investigated by UV-visible, steady state and time resolved fluorescence spectra and PM3 method. In protic solvents, the normal emission originates from a locally excited state and the longer wavelength emission is due to intramolecular charge transfer (TICT). Labetalol forms a 1:2 complex and pseudoephedrine forms 1:1 complex with β-CD. Nanosecond time-resolved studies indicated that both molecules show triexponential decay. Thermodynamic parameters (ΔG, ΔH, ΔS) and HOMO, LUMO orbital investigations confirm the stability of the inclusion complex. The geometry of the most stable complex shows that the aromatic ring is deeply self included inside the β-CD cavity and intermolecular hydrogen bonds were established between host and guest molecules. This suggests that hydrophobic effect and hydrogen bond play an important role in the inclusion process.     

诺氟沙星与环糊精的超分子体系

研究了诺氟沙星与β-环糊精(简称β-CD)及其两种衍生物羟丙基-β-环糊精(简称Hp-β-CD)、甲基-β-环糊精(简称Me-β-CD)形成的超分子体系.利用荧光光谱法测定了超分子体系的包结常数和包结比,及其热力学参数.诺氟沙星与3种环糊精均形成1∶1稳定的包合物,诺氟沙星与β-CD、Me-β-CD及Hp-β-CD作用...     

Azo-hydrazo Tautomerism and Inclusion Complexation of 1-phenylazo-2-naphthols with Various Solvents and β-cyclodextrin

Spectral characteristics of sudan I (SDI), sudan II (SDII) and mordant violet-5 (MV5) have been studied in various solvents and β-cyclodextrin (β-CD). The inclusion complex of the above molecules with β-CD was analyzed by UV-visible, fluorometry, and DFT methods. The solvent study shows that azo-hydrazo tautomer is present in these molecules. The increase in the fluorescence intensity and a large bathochromic shift in the S₁ state indicate these molecules forms 1:1 inclusion complex with β-CD.     

Conformational Analysis of the Inclusion Complex of 3-Hydroxy-2-Naphthalenecarboxylate Anion with Heptakis-(2,3,6-Tri-Omethyl)-β-Cyclodextrin by 2D 1Hnmr

Conformational analysis of the inclusion complex of heptakis-(2,3,6-tri-o-methyl)-β-cyclodextrin(TMβ-CD) with the 3-hydroxy-2-naphthalenecarboxylate anion in D₂O was undertaken by ID and 2D ¹HNMR measurements. the results show that the naphthyl group of 3-hydroxy-2-naphthalenecarboxylate anion inserts lengthwise into the TMβ-CD cavity from the 6-OCH₃ side with an angle of the molecular axis.     

Hydroxypropyl-β-Cyclodextrin Enhanced Determination for the Vitamin B<Subscript>12</Subscript> by Fluorescence Quenching Method

A novel fluorescence quenching method for the determination of Vitamin B₁₂(VB₁₂) had been developed. It was based on that the fluorescence intensity of erythrosine sodium(ES) could be enhanced by Hydroxypropyl-β-cyclodextrin(HP-β-CD) due to the formation of inclusion complex (HP-β-CD-ES), while the fluorescence intensity of HP-β-CD-ES was diminished after adding VB₁₂ into the system, and there was a linear relationship between the fluorescence quenching value of the system (ΔF) and the concentration of VB₁₂(c). The mechanism of the determination of VB₁₂was discussed. The results showed that under the optimal conditions, the linear range of calibration curve for the determination of VB₁₂ was 0.0∼2.1 × 10⁻⁵ mol/L, and the detection limit was 1.8×10⁻⁷ mol/ L. It could be satisfactorily applied to the determination of VB₁₂ in injections.     

β-环糊精衍生物对α-苯丙酸包结作用的研究

用紫外光谱法研究了系列β-环糊精衍生物(羟丙基-β-环糊精、羟乙基-β-环糊精和甲基-β-环糊精)对α-苯丙酸的包结作用,考察了不同β-环糊精衍生物对不同存在状态的α-苯丙酸的包结行为。结果说明,α-苯丙酸与β-环糊精衍生物形成的包合物的包合比为1∶1,三种主体环糊精的包结能力强弱顺序为:羟乙基-β-环糊精羟丙基-β-环糊精甲基-β-环糊精。羟丙基-β-环糊精适合包结分子状态的α-苯丙酸,而不易包结离子状态的α-苯丙酸。     

β-cyclodextrin Sensitized Spectrofluorimetry for the Determination of Abiraterone Acetate and Abiraterone

A novel spectrofluorimetric method to determine abiraterone acetate and its active metabolite, abiraterone was developed, based on the fact that fluorescence intensity of abiraterone acetate and abiraterone could be enhanced in β-cyclodextrin (β-CD) due to the formation of the inclusion complex. The inclusion interaction of β-CD and abiraterone acetate and the β-cyclodextrin sensitized spectrofluorimetry was examined. The various factors influencing fluorescence were discussed in details. The results showed that under the optimized conditions, the linear range of calibration curve for the determination of biraterone acetate and abiraterone was 0.20?~?6.0 μg/mL, and the detection limit (LOD) was 6.8 (r?=?0.997) or 6.6 ng/mL (r?=?0.996), respectively. No interference was observed from common co-existing substances or pharmaceutical excipient. The method was successfully applied to the analysis of abiraterone acetate in pharmaceutical formulation and abiraterone in human serum/urine.     

荧光光谱法研究β-环糊精衍生物对氟比洛芬的包结作用

采用荧光光谱法研究了β-CD衍生物对氟比洛芬的包结作用。实验考察了β-CD衍生物种类及其浓度、乙醇含量、离子强度及pH等因素对包结作用的影响。实验结果表明:随β-CD衍生物浓度的增大,荧光强度逐渐增强,其中HP-β-CD的增强效果最明显,即表明HP-β-CD对氟比洛芬的包结作用最强。1/(F-F0)对1/[CD]所作的双倒数曲线为直线,说明氟比洛芬与环糊精形成1∶1的包合物。随离子强度增大,包合作用增强;溶液中乙醇比例和pH越大,HP-β-CD与氟比洛芬包结物的包合作用越弱。     

连翘酯苷/β-环糊精包合物稳定性研究

用饱和溶液法制备了β-环糊精与连翘酯苷的包合物,荧光光谱法对包合物进行了表征。测定了包合物的形成常数及其在293-328K范围内的热力学参数△G、△H、△S。实验表明：包合过程是一个放热过程。连翘酯苷经β-环糊精包合后提高了稳定性,具有一定程度的抗氧化、抗光解性。     

Supramolecular Study on the Interaction Between Ofloxacin and Methyl β-Cyclodextrin by Fluorescence Spectroscopy and its Analytical Application

The supramolecular interaction of ofloxacin (Oflo) and methyl β-cyclodextrin (Mβ-CD) has been examined by UV–vis, IR and fluorescence spectroscopy. The formation of inclusion complex has been confirmed based on the changes of the spectral properties. The results showed that Mβ-CD reacted with Oflo to form an inclusion complex. The Oflo and Mβ-CD complex formed a host-guest complex in 1:1 stoichiometry and inclusion constant (K?=?7.8?×?10^?3 L mol^?1) was ascertained by the typical double reciprocal plots. Furthermore, the thermodynamic parameters (?H°, ?S° and ?G°) associated with the inclusion process were also determined. In addition, solid inclusion complex was synthesized. Based on the significant enhancement of the fluorescence intensity of Oflo produced through complex formation, a simple, accurate, rapid and highly sensitive spectrofluorometric method for the determination of Oflo in pharmaceutical formulation was developed. The measurement of relative fluorescence intensity was carried out at 497 nm with excitation at 296 nm. The factors affecting the inclusion complex formation were studied and optimized. Under the optimum reaction conditions, linear relationships with good correlation coefficients (0.9995) were in the concentration range of 50–350 ng/mL for spectrofluorimetry. The limit of detection (LOD) was 11.5 ng/mL. The proposed method was successfully applied to the analysis of Oflo in pharmaceutical preparation.     

光谱法研究环糊精与艾地苯醌的超分子作用

用荧光光谱法研究了药物艾地苯醌与β-环糊精在溶液中的超分子复合作用,发现在加入β-环糊精后其荧光强度显著增强;Benesi-Hildebrand曲线显示在溶液中它们之间以1∶1的方式结合,包合常数K为412mol/L;紫外滴定实验显示出艾地苯醌的去质子化常数在加入β-CD后与本身的pKa基本一致,说明超分子复合物中艾地苯醌分子中的—OH基团存在于环糊精空腔外面。核磁测试显示在加入β-CD后艾地苯醌的C-11的化学位移向高场移动,而C-11上的氢位移则向低场移动,表明芳环上的甲氧基进入了环糊精的空腔。     

Excimer Emission in Norepinephrine and Epinephrine Drugs with α- and β-Cyclodextrins: Spectral and Molecular Modeling Studies

The inclusion complexation behavior of norepinephrine (NORE) and epinephrine (EPIN) with native cyclodextrins (α-CD and β-CD) were investigated by UV-visible, fluorimetry, time-resolved fluorescence, SEM, TEM, FT-IR, ¹H NMR, DSC, powder XRD and PM3 methods. Single emission was observed in aqueous solution where as dual emission (excimer) noticed in the CD solutions. Both drugs form 1:1 drug-CD complexes in lower CD concentrations and 1:2 CD-drug₂ complexes in the higher CD concentrations. Time-resolved fluorescence studies indicated that both drugs showed single exponential decay in water and biexponential decay in CD. Nano-sized self-aggregated particles of drug-CD were found by TEM studies. Molecular modeling studies indicated that aliphatic chain part of the drug was entrapped in the CD cavity. Thermodynamic parameters and binding affinity of complex formation of the CD were determined according to PM3 method. The PM3 results were in good agreement with the experimental results.     

Inclusion of menadione with cyclodextrins studied by calorimetry and spectroscopic methods

Complex formation of menadione with α‐, hydroxypropyl α‐, β‐, hydroxypropyl‐β‐, methyl‐β‐ and hydroxypropyl‐γ cyclodextrins in aqueous solution at 298.15 K was studied by using isothermal titration calorimetry, ¹H NMR, and UV–vis spectrophotometry. The experimental data indicated the partial insertion of menadione into macrocyclic cavity upon formation of two alternative types of 1:1 inclusion complexes, whose thermodynamic parameters (K, Δ_cG⁰, Δ_cH⁰, and Δ_cS⁰) were calculated. The influence of host size on the complex formation process was analyzed. β‐Cyclodextrin and its hydroxypropylated and methylated derivatives were found more effective binders towards menadione than α‐ and γ‐cyclodextrins. Copyright © 2007 John Wiley & Sons, Ltd.     

Interaction between titanium dioxide nanoparticles and human serum albumin revealed by fluorescence spectroscopy in the absence of photoactivation

Titanium dioxide (TiO₂) nanoparticles (NPs) are widely used as an important kind of biomaterials. The interaction between TiO₂ (P25) at 20 nm in diameter and human serum albumin (HSA) was studied by fluorescence spectroscopy in this work. Under the simulative physiological conditions, fluorescence data revealed the presence of a single class of binding site on HSA and its binding constants (K_a) were 2.18±0.04×10⁴, 0.87±0.05×10⁴, 0.68±0.06×10⁴ M⁻¹ at 298, 304 and 310 K, respectively. In addition, according to the Van’t Hoff equation, the thermodynamic functions standard enthalpy (ΔH⁰) and standard entropy (ΔS⁰) for the reaction were calculated to be −75.18±0.15 kJ mol⁻¹ and −170.11±0.38 J mol⁻¹ K⁻¹. These results indicated that TiO₂ NPs bond to HSA mainly by van der Waals force and hydrogen bonding formation in low dielectric media, and the electrostatic interactions cannot be excluded. Furthermore, the effects of common ions on the binding constant of TiO₂ NPs-HSA complex were discussed.     

Intramolecular Charge Transfer Effects on Flutamide Drug

Spectral characteristics of flutamide drug have been studied in various solvents and β-cyclodextrin (β-CD). The inclusion complex of flutamide with β-CD is analysed by UV-visible, fluorimetry, FT-IR, 1H NMR, SEM, DSC and AM1 methods. In all solvents, flutamide exhibits a dual fluorescence. The longer wavelength emission (A band ∼380 nm) is due to intramolecular charge transfer state (ICT) and the shorter wavelength emission (B band ∼285 nm) originates from a locally excited state. In β-CD, the increase in the fluorescence intensity of ‘A’ band indicates ICT emission enhanced in the β-CD medium. β-CD studies shows isopropyl group is present in the interior part of the β-CD cavity whereas amino and CF₃ groups are present in the outside of the β-CD cavity. A mechanism is proposed to explain the 1:1 inclusion process.