冰片β-环糊精包合物的理化性质考察

目的考察冰片β 环糊精的理化性能。 方法采用薄层析、热重和差热分析、X 射线粉末衍射及红外光谱法对包合物进行理化鉴别 ,采用气相色谱法考察了包合物中冰片的溶解度和体外溶出度。结果薄层析图谱显示 ,冰片被 β 环糊精包合前后的主成分没有发生变化 ,包合物的热重和差热分析曲线、X 射线粉末衍射图谱及红外光谱与冰片、冰片 β 环糊精混合物的图谱具有显著性差异。包合物中冰片在 0 1mol/L盐酸溶液、pH6 6和 pH7 5磷酸盐缓冲液中的溶解度及体外溶出速率均有显著提高。结论冰片被β 环糊精包合后呈现出新的物相特征 ,与冰片相比其理化性质有显著的改变     

肉桂油β-环糊精包合物的理化性质

目的 :考察肉桂油 β 环糊精的理化性能。 方法 :采用薄层层析、X 射线粉末衍射及红外光谱法对包合物进行理化鉴别 ,采用高效液相色谱法考察包合物中桂皮醛的溶解度和体外溶出度。结果 :薄层层析图谱显示 ,肉桂油被 β 环糊精包合前后的主成分没有发生变化 ,包合物的X 射线粉末衍射图谱及红外光谱与肉桂油、肉桂油 β 环糊精混合物的图谱差异具有显著性。包合物中桂皮醛在 0 .1mol·L-1盐酸溶液、pH6 .6和 pH7.5磷酸盐缓冲液中的溶解度及体外溶出速率均有显著提高。结论 :肉桂油被 β 环糊精包合后呈现出新的物相特征 ,与肉桂油相比其理化性质有较显著的改变。     

Preparation & characterization of solid inclusion complex of cefpodoxime proxetil with beta-cyclodextrin

Cefpodoxime proxetil (CPDX-PR) is an oral cephalosporin antibiotic with poor aqueous solubility and bioavailability. Effect of beta-cyclodextrin on aqueous solubility and dissolution rate of cefpodoxime proxetil was evaluated by the formation of solid inclusion complexes in 1:2 molar ratio of drug: cyclodextrin. Phase solubility study was carried out whereby a typical B's type curve was obtained thus, indicating a 1:2 stoichiometric ratio for optimum complex formation. Solid inclusion complexes in 1:2 molar ratios were prepared by using methods such as physical mixture, solvent evaporation and freeze drying. Prepared complexes were characterized by fourier transform infrared spectroscopy (FT-IR) differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and scanning electron microscopy (SEM). Results of in vitro studies appraised of an increased solubility and dissolution rate of cefpodoxime proxetil on complexation with beta- cyclodextrin (P < 0.05) as compared to CPDX-PR alone. Amongst the complexes prepared by different methods, the complex prepared by freeze drying showed the highest dissolution rate (P< 0.01). The in vitro antimicrobial activity of cefpodoxime proxetil and its freeze dried complex (1:2) was studied against both antibiotic-susceptible and antibiotic-resistant clinical isolates of Neisseria gonorrhoeae. The freeze dried complex (1:2) inhibited all penicillin-susceptible strains and penicillinase-producing strains at 0.015 microg/ml concentration. Chromosomally resistant strains which were not responsive to penicillin were inhibited by the complex at 0.125 microg/ml concentration. The study revealed that complexation of cefpodoxime proxetil with beta-cyclodextrin effectively enhanced the aqueous solubility and in vitro antibacterial activity.     

Preparation and study the 1:2 inclusion complex of carvedilol with beta-cyclodextrin

An inclusion complex of beta-cyclodextrin with carvedilol was prepared by using a convenient new method of microwave irradiation. Phase-solubility studies demonstrated the ability of beta-cyclodextrins to complex with carvedilol and increase drug solubility. The structure of inclusion complex was determined by fluorescence spectroscopy and 1H NMR, 13C NMR measurements in solution. The solid inclusion was characterised by infrared spectroscopy, differential scanning calorimetry (DSC) and element analysis. These experimental results confirmed the existence of 1:2 inclusion complex of carvedilol with beta-cyclodextrin, the formation constant of complex was determined by the fluorescence method. Molecular modeling predicted the energy-minimized structure of the complex.     

Spectrophotometric and electrochemical study of the inclusion complex between beta-cyclodextrin and furnidipine

Inclusion complexation between furnidipine (2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-tetrahydrofurfuryl 5-methyl diester), a calcium-channel antagonist, and beta-cyclodextrin (beta-CyD) was studied in aqueous solution by using both spectrophotometric and electrochemical measurements. The phase solubility profile was classified as A(L)-type, indicating the formation of 1:1 stoichiometric inclusion complex of furnidipine with beta-CyD. Based on the spectrophotometric absorbance's variations, a formation constant value, K(f), of 156 M(-1) was determined. Electrochemical measurements using chronocoulometric experiments were used for the determination of the diffusion coefficients. In absence of beta-CyD, a diffusion coefficient value of 4.32 x 10(-6) cm2 s(-1) was obtained for furnidipine. The addition of beta-CyD produced a decrease of 30% for the diffusion coefficient. Formation of inclusion complexes of furnidipine with beta-CyD was proved to increase more than three times the solubility of furnidipine.     

WB852-β环糊精包合物的研究

环糊精(cyclodextrin,CD)的发现已近百年,其基础和应用方面的研究至今仍相当活跃,由于环糊精优良的理化性质和生物学特性,可使不稳定的药物包含于环糊精分子内,因此在某种程度上切断药物分子与周围化学环境的联系,而提高药物的稳定性。本文就抗癌抗炎新药WB_(852)~((2,3))的环糊精包合物进行研究,以期提高其化学稳定性。     

卡马西平β-环糊精包合物的制备及其包合作用的考察

目的为提高卡马西平的溶解性,采用饱和水溶液法制备卡马西平β-环糊精包合物并对其工艺和包合作用进行研究。方法以包封率、收率、载药量为指标,采用综合评分法,通过正交设计优选最佳包合工艺。采用连续递变浓度法测定包合比,绘制不同温度下的相溶解度曲线,测定包合常数和热力学参数。结果最佳包合工艺为包合温度80℃,卡马西平与β-环糊精物质的量比为1∶1,包合时间为1 h。所测定的包合物的包封率为93%,收率为98.6%,载药量为16%。相溶解度曲线为AL型,于25、35、45和55℃下包合常数分别为499.8、673.2、916.9和1 240.8 L·mol-1,吉布斯自由能(ΔG)分别为-15.4、-16.7、-18.0和-19.4 k J·mol-1,焓变(ΔH)为24.7 k J·mol-1,熵变(ΔS)为134.3 J·mol-1·K-1。结论所制备的卡马西平β-环糊精包合物,溶解性显著提高,包合过程是自发进行的熵驱动下的吸热反应。     

Allylthiosulfinate: beta-cyclodextrin inclusion complex: preparation, characterization and microbiological activity

An allylthiosulfinate: beta-cyclodextrin inclusion complex was synthesized and characterized using X-ray crystallography, IR spectroscopy, thermal analysis and nuclear magnetic resonance. The microbiological activity of the complex was tested on available fungi (Candida albicans ATCC 10231, Aspergillus niger ATCC 16404) and bacteria (Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027). In small concentrations, the complex inhibited the growth of the microorganisms tested. The most susceptible microorganism was Candida albicans ATCC 10231, and the least susceptible Pseudomonas aeruginosa ATCC 9027.     

Preparation and characterization of inclusion complexes of prazosin hydrochloride with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin

The slightly water-soluble drug prazosin hydrochloride (PRH) and its inclusion with either beta-cyclodextrin (betaCD) or hydroxypropyl-beta-cyclodextrin (HPbetaCD) were investigated. The phase solubility profiles of PRH with betaCD and HPbetaCD were classified as B(s)- and A(L)-types, respectively. Stability constants with 1:1 molar ratio were calculated from the phase solubility diagrams and the solubility of PRH could be enhanced by 27.6% for betaCD and 226.4% for HPbetaCD, respectively. Binary systems of PRH with betaCD or HPbetaCD prepared by various methods were characterized by differential scanning calorimetry and Fourier transformation-infrared spectroscopy. It could be concluded that PRH could form inclusion complex with either betaCD or HPbetaCD. The dissolution profiles of inclusion complexes were determined and compared with those of PRH alone and their physical mixtures. The dissolution rate of PRH was increased by betaCD and HPbetaCD inclusion complexation remarkably. Both the preparation technique and nature of the carriers played important roles in the dissolution performance of the systems. All the systems with HPbetaCD showed better performance than the corresponding ones with betaCD.     

Phase solubility and inclusion complex of itraconazole with beta-cyclodextrin using supercritical carbon dioxide

Phase-solubility techniques were used to assess the formation of inclusion complex between itraconazole and beta-cyclodextrin. The stability constant and free energies of transfer of itraconazole from aqueous solution to the cavity of beta-cyclodextrin were calculated. Itraconazole solubility in supercritical carbon dioxide (SC CO(2)) was measured at different temperatures and pressures. Drug formulations of itraconazole were prepared by complexation of the drug into beta-cyclodextrin using SC CO(2). Effects of temperature and pressure on inclusion yield of the prepared complexes were studied. The solvent-free inclusion complexes obtained from this method were characterized by UV spectroscopy, differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy and compared to those obtained from physical mixing and coprecipitation methods. Results showed that beta-cyclodextrin significantly improved solubility of itraconazole in aqueous solutions. The free energies of transfer of itraconazole from aqueous solution to the cavity of beta-cyclodextrin increased negatively with increasing beta-cyclodextrin concentration. Higher inclusion yields were obtained in the SC CO(2) method compared to physical mixing and coprecipitation methods. Both temperature and pressure had significant effects on itraconazole solubility in SC CO(2) and the inclusion yield of the complex prepared by SC CO(2) method.     

Anticryptosporidial activity of furan derivative G1 and its inclusion complex with beta-cyclodextrin

The capacity of beta-cyclodextrin (betaCD) to form a complex with a new furanic derivative, G1, was investigated. Interactions of the drug and betaCD in solution and in the solid state were studied using phase solubility techniques, thermal methods, X-ray, and IR spectroscopy. Preparation of a kneaded mix of G1/betaCD increased both the aqueous solubility and the dissolution rate of the furan derivative. The anticryptosporidial efficacies of the drug and of the inclusion complex were evaluated using a suckling murine model. Oral administration of G1 considerably decreased the intensity of the infection, but betaCD showed similar anticryptosporidial activity to that of the betaCD-G1 complex and higher activity than G1 alone.     

Availability of NSAIDH beta-cyclodextrin inclusion complexes

The diffusion of a series of non steroidal antiinflammatory drugs through a silicone rubber membrane has been studied from suspensions both of the free and beta-cyclodextrin complexes forms at different pH values of the medium. Higher diffusion rates of the complexed forms as compared with the free ones and a rate-limiting effect of the apparent stability constant in the diffusion of the complexes were observed.     

Study on the inclusion complex between beta-cyclodextrin and celecoxib by spectrofluorimetry and its analytical application

The supramolecular interaction of celecoxib (chemically 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzene sulfonamide) and beta-cyclodextrin (beta-CD) has been studied by spectrofluorimetry. The results showed that beta-CD reacted with celecoxib to form an inclusion complex. 1:1 stoichiometry for beta-CD-celecoxib complex was established and its association constant at different temperatures was calculated by applying a non-linear regression method to the change in the fluorescence of celecoxib that brought about by the presence of beta-CD. The thermodynamic parameters (DeltaH degrees, DeltaS degrees and DeltaG degrees) associated with the inclusion process were also determined. Based on the significant enhancement of the fluorescence intensity of celecoxib produced through complex formation, a simple, rapid and highly sensitive spectrofluorimetric method for the determination of celecoxib in aqueous solution in the presence of beta-CD was developed. The measurement of relative fluorescence intensity was carried out at 390 nm with excitation at 270 nm. A linear relationship between the fluorescence intensity and celecoxib concentration was obtained in the range of 0.1-4.0 microg ml-1, with a correlation coefficient of 0.9996. The detection limit was 7.29 ng ml-1 and the relative standard deviation was 1.28%. The method was successfully applied to the determination of celecoxib in pharmaceutical preparations.     

氟比洛芬羟丙基-β-环糊精包合物的研制

目的：制备氟比洛芬羟丙基-β-环糊精包合物。方法：采用溶液搅拌法制备氟比洛芬羟丙基-β-环糊精包合物，利用正交试验设计优化包合物的制备工艺，采用相溶解度法测定包合物的组成比例和包合稳定常数，采用差示扫描量热法和X_射线衍射法对包合物进行鉴定。结果：通过正交试验筛选的最优处方为氟比洛芬与羟丙基-β-环糊精的投料摩尔比为1：2，包合温度60℃，包合时间6h。结论：氟比洛芬与羟丙基-β-环糊精可形成稳定的包合物。     

氧氟沙星包合物的制备、表征及其包合机制的分析

目的：研究氧氟沙星与环糊精（包括β-环糊精和羟丙基β-环糊精）包合物的制备过程,包合物的结构表征以及包合机制。方法：采用超声法制备包合物,并采用各种不同的方法对形成的包合物进行表征和识别,包括荧光光谱法、紫外-可见分光光度法和核磁共振法等。荧光光谱法计算包合常数（K）以及包合比（n）,同时研究室温条件下不同浓度的环糊精及其衍生物以及不同的酸碱度对包合作用的影响,核磁共振法用于研究包合机制。结果：溶液中不同的pH对氧氟沙星的存在形式影响不同;不同pH条件下,环糊精对氧氟沙星具有不同的包合能力,其中β-环糊精（β-CD）在中性条件下更容易与氧氟沙星进行包合,其包合常数为1 300;而羟丙基β-环糊精（HP-β-CD）更容易在酸性性条件下与氧氟沙星进行包合,其包合常数为1 640。在研究的浓度范围内,环糊精分子与氧氟沙星分子是按1：1形成包合物的。结论：氧氟沙星与环糊精在实验条件下形成了稳定的包合物,氧氟沙星分子是从环糊精及其衍生物的大口端包合进入到空腔内。     

A preliminary study of beta-cyclodextrin/metoprolol tartrate inclusion complex for potential enantiomeric separation

The inclusion complex formation between Metoprolol tartarata (MeT) and β-cyclodextrin (β-CD) has been investigated using hyperchromic shift at λ_max 274.4 nm of MeT. Different parameters such as stirring time, solvent composition (aqueous and aqueous/methanol solutions with methanol content up to 50%), pH values 4.0 and 8.0 were established for optimal inclusion complex formation and confirmed two stoichiometric compositions 1:1 and 1:2. Preliminary data on usage of MeT/β-CD complex in reversed-phase HPLC indicate the potential application of this complex as a kind of pre-column derivatization for enantiomeric separation of β₁-blockers.     

Preparation and characterization of inclusion complexes of a cationic beta-cyclodextrin polymer with butylparaben or triclosan

The preparation of a cationic β-cyclodextrin polymer (CPβCD) and its complexes with butylparaben and triclosan were reported in this paper. FT-IR and 2D ¹H–¹H gCOSY NMR spectra confirmed that the antibiotics could be included inside of the lipophilic cavities of CPβCD. The formation of complexation of CPβCD with the antibiotics significantly improved the water solubility. The solubility of the antibiotics linearly increased with the concentration of CPβCD, and the values of the association constant K_1:1 of the butylparapben/CPβCD and triclosan/CPβCD complexes were 3800 and 3082 M⁻¹, respectively. The results also suggested that it was easier for butylparaben, which had relative smaller molecular size, to form the complexes with CPβCD than triclosan. Due to the targeting effect after the complexation with CPβCD, the antimicrobial activity of butylparaben can be significantly improved. Meanwhile, this improvement effect was not obvious for triclosan.     

Stability of diclofenac sodium in the inclusion complex with beta-cyclodextrin in the solid state

The aim of this study was to characterize the thermal stability of diclofenac sodium both alone and in the inclusion complex with beta-cyclodextrin in the solid state, by determination of the number of the products of its decomposition, which were identified by GC-MS. The molar ratio of diclofenac sodium in the inclusion complex with beta-cyclodextrin was 1:1. The decomposition of diclofenac sodium both alone and in inclusion complex with beta-cyclodextrin occurred according to the first-order reaction. The HPLC of the samples thermostated at 80 degrees C gave five products of decomposition, which were identified by GC-MS. Diclofenac sodium in the inclusion complex with beta-cyclodextrin was more thermally stable. Thermal decomposition of diclofenac sodium leads to formation of five products, of which 4-chloro-10H-9-acridinone had not been reported previously in the literature.     

In-vitro evaluation of cinnarizine as a competing agent to beta-cyclodextrin inclusion complexes: effect of cinnarizine on the membrane permeation rate of progesterone from its beta-cyclodextrin inclusion complex

The use of competing agents is considered a powerful tool for the development of a drug-delivery system with drug/cyclodextrin inclusion complexes. However, there are very few studies examining this issue. To explain this phenomenon, it was thought that a competing agent with a sufficiently high stability constant had not yet been reported. In this study, cinnarizine (CN), which has a high stability constant with beta-cyclodextrin (beta-CD) and unique solubility characteristics, was selected, and its ability as a competing agent was examined in a membrane permeability study. The permeability study showed that the permeation rates of the drugs flurbiprofen, progesterone, and spironolactone decreased with their stability constants with the addition of beta-CD. In one of the drugs, progesterone (Pro), the decrease was restored by the addition of CN. The amount of CN added was a 1:1 molar ratio to the amount of Pro. However, no similar action was induced with the addition of DL-phenylalanine (Phe) in the permeation study at the 1:5 (Pro:Phe) molar ratio. These finding indicate that CN acts as a competing agent, and its action is much stronger than that of Phe.     

马蔺子素-羟丙基-β-环糊精包合物的制备、鉴定及包合作用

目的制备和鉴定马蔺子素-羟丙基-β-环糊精包合物，并考察马蔺子素与HP-β-CD之间的包合作用及构成摩尔质量比。方法通过冷冻干燥法制备马蔺子素-羟丙基-β-环糊精包合物，采用摩尔梯度法和连续递变法考察了包合物中主客分子之间的包合摩尔比；采用X射线衍射(XRD)和差示扫描量热法(DSC)对包合物进行了鉴定。结果主客分子摩尔梯度和反应热力学结果显示，25 ℃,35 ℃和45 ℃下HP-β-CD与马蔺子素包合摩尔质量比为2∶1，此时具有最大的增溶特性和较大的结合常数，其冻干粉经鉴别已形成包合物。结论马蔺子素包合物能显著增大药物的溶解度和稳定性。