α-氨基酸及其酯化物侧链对其β-环糊精复合物稳定常数的影响

为了探索α-氨基酸及其酯化物的侧链R基团对其与环糊精非共价复合物结合强度的影响,将一定摩尔比的β-环糊精(β-CD)分别与L型正缬氨酸(n-Val)、亮氨酸(Leu)、苯丙氨酸(Phe)、天冬氨酸(Asp)、天冬氨酸-4-苄酯(Asp-4-benzyl ester)和天冬氨酸-4-叔丁酯(Asp-4-t-butyl ester)在室温下混合,反应平衡后采用电喷雾电离质谱进行竞争反应检测,并以改进的质谱滴定结合曲线拟合法计算结合常数.结果表明,它们均可形成摩尔比为1∶1的非共价复合物.在2组竞争反应中,复合物的结合强度顺序分别为[β-CD∶Asp-4-benzyl ester+H]~+[β-CD∶Asp-4-t-butyl ester+H]~+[β-CD∶Asp+H]~+以及[β-CD∶Phe+H]~+[β-CD∶Leu+H]~+[β-CD∶n-Val+H]~+.质谱滴定曲线拟合法测得[β-CD∶n-Val+H]~+,[β-CD∶Asp+H]~+,[β-CD∶Asp-4-t-butyl ester+H]~+,[β-CD∶Asp-4-benzyl ester+H]~+,[β-CD∶Leu+H]~+和[β-CD∶Phe+H]~+的稳定常数(lgK_(st))分别为1.81,2.54,3.14,3.26,3.36和3.67,结合强度依次增强.竞争反应的定性分析结果与质谱滴定定量法测得结合强度结果的趋势一致.由于所选用的α-氨基酸及其酯化物客体的羧基端(—COOH)和氨基端(—NH_2)均相同,且都为亲水基团,仅有侧链R基团不同,因此在溶液中客体分子受疏水驱动与β-CD主体靠近并结合时,侧链R基团的疏水力和极性2个因素起重要作用.由于客体分子体积小,其碳端的羧基还可与β-CD大口或小口边缘的羟基形成氢键,使复合物更加稳定.     

Theoretical and experimental study of the inclusion complexes of ferulic acid with cyclodextrins

The inclusion complexation behaviour of ferulic acid (FA) with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated by UV–vis, fluorescence and ¹H NMR spectroscopy. Since the guest may exist in either anionic or neutral form, the experiments were performed at different pH values. The stoichiometry and association constants of the complexes were determined by nonlinear regression analysis. The phase-solubility studies indicated that the water solubility of FA was improved through complexation with β-CD and HP-β-CD. An increase in the antioxidant reactivity was observed when inclusion complexes that FA formed with CDs were studied. Based on the NMR data, the spatial configurations of FA/β-CD and FA/HP-β-CD complexes were proposed, which suggested that FA entered into the cavity of β-CD from the narrow side, with the lipophilic aromatic ring and ethylenic moieties inside the CD cavity, and the –COOH group was close to the wider rim and exposed outside the cavity. A theoretical study of the complexes using molecular modelling gives the results in good agreement with the NMR data.     

Study on the complexation of isoquercitrin with β-cyclodextrin and its derivatives by spectroscopy

The inclusion complexes of isoquercitrin (IQ) with cyclodextrins (CDs) including β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and dimethyl-β-cyclodextrin (DM-β-CD) have been investigated using the methods of steady-state fluorescence, UV-vis absorption and induced circular dichroism. The stoichiometric ratio of the three complexes was found to be 1:1 and the stability constants (K) were estimated from spectrofluorometric titrations, as well as the thermodynamic parameters. Maximum inclusion ability was measured in the case of DM-β-CD due to the increased hydrophobicity of the host cavity, followed by HP-β-CD and β-CD. The effect of pH on the complexation process was also quantitatively assessed. IQ exists in different molecular forms depending on pH and β-CDs were most suitable for inclusion of the neutral form of IQ. The phase-solubility diagrams obtained with β-CD, HP-β-CD and DM-β-CD were all classical A_L type. And DM-β-CD provided the best solubility enhancement, 12.3-fold increase compared to 2.8- and 7.5-fold increase for β-CD and HP-β-CD. The apparent stability constants obtained from the solubility data at 25 °C were comparable with those obtained from the fluorescence assays. Moreover, ¹H NMR was carried out, which revealed that the IQ favorably inserted into the inner cavity from the chromone part instead of the phenyl part, which was in agreement with molecular modeling studies.     

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 K_d1 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 K_d1 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. K_d1 for the Li⁺ complexes of β-CD is smaller than that of DM-β-CD due to its steric effect of the partial substituted -CH₃. The Kd1 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.     

Enrofloxacin inclusion complexes with cyclodextrins

Inclusion complexes using α-, β-, γ-, and hydroxypropyl-β-CD (HP-β-CD) were produced with the antibiotic enrofloxacin, with the aim of increasing its solubility by complexation. Phase solubility diagrams were obtained, to confirm the formation of inclusion complexes, and to determine the solubility enhancement and stability constant of each complex. Enrofloxacin inclusion in β-CD showed the highest value of the complex stability constant (35.56?mmol?L^?1), but the greatest increase in solubility was obtained using HP-β-CD reaching a 1258% increase over enrofloxacin solubility in the absence of CD. The order of highest enrofloxacin solubility achieved was: HP-β-CD?>?α-CD?>?γ-CD?>?β-CD. In addition, formation of complexes was confirmed by differential scanning calorimetry and thermogravimetry, applied to the complexes obtained by the kneading technique. The influence of citric acid, alone or as an adjunct of β-CD, on the solubility of enrofloxacin was also determined. A solution of 15?mmol?L^?1 citric acid dissolved 10?g?L^?1 of enrofloxacin, but a gradual increase in β-CD concentration in the presence of citric acid did not increase the degree of solubilization of enrofloxacin.     

抗抑郁化合物SIPI5838和环糊精分子非共价复合物的研究

报道了用电喷雾电离质谱(ESI-MS), 并结合紫外分光光度法及溶解度实验, 研究一种新型的具有自主知识产权的抗抑郁化合物SIPI5838与α-环糊精(CD)和β-环糊精(CD)分子生成的非共价复合物. 质谱测量结果表明, 在溶液中, SIPI5838分子可以与环糊精分子之间生成非共价复合物, 且两者之间的配比关系为1∶1. 这些非共价复合物的形成可以显著地提高这种抗抑郁化合物在水溶液中的溶解度, 使得它作为高效的口服或注射药物成为可能. 另外, 还用紫外分光光度法和溶解度实验对液相中非共价复合物的形成进行了辅助研究, 这些结果均显示了非共价复合物的生成. 根据溶解度实验结果, 计算了SIPI5838和两种环糊精分子在液相中的生成常数, 它们分别为SIPI5838-β-环糊精: 1.83×103 mol－1•L, SIPI5838-α-环糊精: 3.15×101 mol－1•L. 两种非共价复合物的稳定程度为β-环糊精-SIPI5838＞α-环糊精-SIPI5838.     

Investigation on the inclusion behaviour of baicalein with β-cyclodextrin and derivatives and their antioxidant ability study

The formation of the complexes of baicalein (Ba) with β-cyclodextrin (β-CD) and β-CD derivatives (HP-β-CD and Me-β-CD) was studied by UV–vis absorption spectroscopy, fluorescence method, nuclear magnetic resonance spectroscopy and phase-solubility measurement. The solid–inclusion complexes of Ba with CDs were synthesised by the co-precipitation method. The characterisations of the solid–inclusion complexes have been proved by infrared spectra and differential scanning calorimetry. Experimental conditions including the concentration of various CDs and media acidity were investigated in detail. The results suggested that the inclusion ratio of HP-β-CD with Ba was the highest among the three kinds of CDs. The binding constants (Ks) of the inclusion complexes were determined by fluorescence method and phase-solubility measurement. Kinetic studies of DPPH√ with Ba and CDs complexes were also done. The results indicated that the Ba/HP-β-CD complex was the most reactive form.     

A comparative study of inclusion complexes of flunarizine with alpha (α-CD) and beta-cyclodextrin (β-CD)

A detailed NMR (¹H, COSY, and ROESY) spectroscopic study of complexation of Flunarazine (FL) with α- and β-CD was carried out. ¹H NMR titration studies confirmed the formation of FL/α-CD and FL/β-CD complexes as evidenced by chemical shift variations of the proton resonances of both the CDs and FL. The stoichiometry of the complexes was determined to be 1:2 (FL/α-CD) and 1:1 (FL/β-CD) and overall binding constants were also calculated. It was confirmed with the help of ROESY spectral data that only one of the F-substituted aromatic ring and phenyl ring penetrate the α-CD cavity while both F-substituted aromatic rings as well as phenyl ring penetrates the β-CD cavity during complexation. The binding modes of FL/CD cavity interactions derived from ROESY experimental data show that the resulting complex of FL with β-CD possesses better induced fit interaction as compared to α-CD, which is responsible for the enhanced molecular stability with β-CD in comparison to α-CD. The mode of penetration of guest into the CD cavity and structures of the complexes has been established.     

Study on preparation and inclusion behavior of inclusion complexes between β-cyclodextrin derivatives with benzophenone

In the paper, the two chemically modified β-cyclodextrin derivatives of 4,4´-diaminodiphenyl ether-bridged-bis-β-cyclodextrins (ODA-bis-β-CD) and p-aminobenzenesulfonic acid-β-cyclodextrin (ABS-β-CD) were synthesized, and then these two β-cyclodextrin derivatives were respectively formed into inclusion complexes with benzophenone (BP) by co-precipitation method. The structure of the inclusion complexes were characterized by UV/vis spectroscopy, FT-IR spectroscopy, elemental analysis, ¹H NMR spectroscopy and XRD. Spectral titration was performed to study the inclusion behavior of the inclusion complexes. These experiments indicated that two inclusion complexes were formed at a stoichiometric ratio of 1:1 and the inclusion stability constants at different temperatures were calculated using the Benesi–Hildebrand (B–H) equation. The thermodynamic parameters (ΔG°, ΔH°, ΔS°) were obtained. As a result, it was found that the two chemically modified β-cyclodextrins containing BP were exothermic and spontaneous process (ΔG°?<?0), and the processes of inclusion complexation were mainly enthalpy driven with negative or minor negative entropic contribution.     

Complexation of hydroxytyrosol with β-cyclodextrins. An efficient photoprotection

The complexation of the potent olive oil antioxidant hydroxytyrosol (HT) with commercial β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous solutions has been studied for the first time. The 1:1 stoichiometries of the complexes were evidenced by Job’s plot and the association constants were determined by linear regressions from Scott’s method. The geometry of the HT/β-CD complex was elucidated by 2D-ROESY experiments, suggesting insertion of the catechol moiety with the hydroxyalkyl chain directed to the primary rim. The antioxidant activity of encapsulated HT was also evaluated by scavenging of the stable DPPH radical, observing an improvement of the scavenging activity upon increase of the cyclodextrin concentration. Complexation of HT with β-CD also provided a strong photoprotection of the polyphenolic compound upon irradiation with UV (λ=254 nm).     

Structural study of the inclusion compounds of thymol, carvacrol and eugenol in β-cyclodextrin by X-ray crystallography

The crystal structures of the inclusion compounds of thymol, carvacrol and eugenol, (components of essential oils of vegetable origin) in β-cyclodextrin have been determined. Thymol/β-CD crystallizes in the space group P1 containing two host molecules in its asymmetric unit whereas both carvacrol/β-CD and eugenol/β-CD complexes crystallize in the space group C2. In all three complexes two host molecules form head-to-head dimers their guest/host stoichiometry being: 1/2 (carvacrol/β-CD), 2/2 (thymol/β-CD) and 3/2 (eugenol/β-CD). In the cases of the thymol/β-CD and the carvacrol/β-CD complexes the β-CD dimers are arranged according to the channel packing mode. The accommodation of the geometrical isomer guests is performed solely by their hydrophobic groups revealing the leading role of the hydrophobic driving forces in the complexation process whereas the position of their hydroxyl group affects the stoichiometry of the formed dimeric complexes. In the case of the eugenol/β-CD dimeric complex one guest molecule is found lying between the β-CD groups in a sandwich fashion whereas the other two symmetry related guests protrude outwards the narrower rim of the hosts with only their hydrophobic allyl-chain located inside the hosts’ cavities. This arrangement prohibits the formation of a channel and the observed crystal packing is that of a Tetrad mode.     

Inclusion complexes of fluconazole with β-cyclodextrin: physicochemical characterization and in vitro evaluation of its formulation

Fluconazole (FZ) is a triazole antifungal drug administered orally or intravenously. It is employed for the treatment of mycotic infections. However, the efficacy of FZ is limited with its poor aqueous solubility and low dissolution rate. One of the important pharmaceutical advantages of cyclodextrins is to improve pharmacological efficacy of drugs due to increasing their aqueous solubility. The aim of present study was to prepare an inclusion complex of FZ and β-cyclodextrin (β-CD) to improve the physicochemical and biopharmaceutical properties of FZ. The effects of β-CD on the solubility of FZ were investigated according to the phase solubility technique. Complexes were prepared with 1:1 M ratio by different methods namely, freeze-drying, spray-drying, co-evaporation and kneading. For the characterization of FZ/β-CD complex, FZ amount, practical yield %, thermal, aqueous solubility, XRD, FT-IR and NMR (¹H and ¹³C) analysis were performed. In vitro dissolution from hard cellulose capsules containing FZ/β-CD complexes was compared to pure FZ and its commercial capsules and evaluated by f₁ (difference) and f₂ (similarity) factors. Paddle method defined in USP 31 together with high pressure liquid chromatographic method were used in in vitro dissolution experiments. It was found that solubility enhancement by FZ/β-CD complexes depends on the type of the preparation method. High release of active agent from hard cellulose capsules prepared with β-CD complexes compared to commercial capsules was attributed to the interactions between β-CD and active agent, high energetic amorphous state and inclusion complex formation.     

Inclusion complexes with cyclodextrin and usnic acid

Molecular inclusion complexes of usnic acid (UA) with β-cyclodextrin (β-CD) and 2-hydroxypropyl β-cyclodextrin (HP β-CD) were prepared by the co-precipitation method in the solid state in the molar ratio of 1:1. Structural complexes characterization was based on different methods, FTIR, ¹H NMR, XRD and DSC. Parallel to the complex by the above methods, corresponding physical mixtures of UA with cyclodextrins and complexing agents (β-CD, HP β-CD and UA) were analyzed. The results of DSC analysis showed that, at around 200 °C, the endothermal peak in the complexes with cyclodextrins originating from the UA melting has disappeared. Complex diffractogram patterns do not contain peaks characteristic for the pure UA. They are more appropriate to cyclodextrin diffractogram. This fact points to the molecular encapsulation of UA in the cyclodextrin cavity. Chemical shifts in ¹H NMR spectra after the inclusion of UA into the cyclodextrin cavity, especially H-3 protons (0.0012 and 0.0102 ppm in the β-CD and HP β-CD, respectively) and H-5 and H-6 (0.0134 ppm) and hydrogen from CH₃ (0.0073 ppm) HP β-CD also points to the formation of molecular inclusion complexes. The improved solubility of UA in water was achieved by molecular incapsulation. In the complex with β-CD the solubility is 0.3 mg/cm³, with HP β-CD 4.2 mg/cm³ while the uncomplexed UA solubility is 0.06 mg/cm³. The microbial activity of UA and both complexes was tested against eight bacteria and two fungi and during the test no reduced activity of UA in the complexes was observed.     

Preparation of β-cyclodextrin-polyaniline complex in supercritical CO2

A method is proposed to prepare β-cyclodextrin (β-CD)/polyaniline (PANI) inclusion complex. In this route, benzoyl peroxide (BPO, the oxidant) is first encapsulated into the cavity of β-CD. Aniline is then carried into the cavity of β-CD by supercritical (SC) CO₂, which polymerizes in situ to form inclusion complex. The product is characterized by FT-IR, UV-Vis, ¹H NMR and XRD techniques. The results suggest that the columnar inclusion complexes may be formed.     

In-situ thermal crosslinked PA66/β-cyclodextrin/PA66 nanofibrous membranes with high mechanical strength for removal of heavy metal ions by flow through adsorption

β-cyclodextrin (β-CD) based materials have been studied widely as adsorbents and filter membranes for removing pollutants in air or water applications. The present study aimed to develop a sandwich structure of eletrospun nanofibrous membrane based on β-cyclodextrin and PA66 to achieve the high mechanical strength and flow-through adsorption of heavy metal ions in water. The surface and cross section morphology of PA66/β-cyclodextrin/PA66 nanofibrous membranes (PA66/β-CD/PA66 NMs) were examined using scanning electron microscopy (SEM). The physicochemical and mechanical properties of PA66/β-CD/PA66 NMs were analyzed by differential scanning calorimetry (DSC), thermogravimetric (TG) analysis and universal testing machine. The diameter of β-CD and PA66 electrospun fibers are 300–400 nm and 20–40 nm respectively. PA66/β-CD/PA66 NMs show a loosely arranged fibers and layer by layer structure. The tensile strength increases remarkably for PA66/β-CD/PA66 NMs, from 1.33 MPa of β-CD NMs to 23.17 MPa and the Young's modulus increases from 34.8 MPa to 253.3 MPa. The mechanical behavior of PA66/β-CD/PA66 NMs is a typical brittle fracture, and its microcosmic fracture diagrams are also involved. TGA/DSC results confirm the thermal crosslinking reaction is effective and complete. On the basis of SEM, DSC, TG and mechanical behavior analysis results, the molecular mechanism of in situ thermal crosslinking reaction is discussed. Fe³⁺、Ni²⁺ were used to confirm the ability to absorb heavy metal ions of PA66/β-CD/PA66 NMs. In conclusion, PA66/β-CD/PA66 NMs could be a promising solution for removal of metal ions by flow-through adsorption.     

The detection of biomarkers in evaporite matrices using a portable Raman instrument under Alpine conditions

The binding of rhodamine 6G and hydroxy propyl β-cyclodextrin (Hβ-CD) was investigated measuring fluorescence and absorption at pH 7.0. The solid inclusion complex of Rh6G and Hβ-CD has been studied by Ultraviolet (UV) spectroscopy, Fluorimetry, Fourier Transform Infrared (FTIR), (1)H Nuclear Magnetic Resonance ((1)HNMR) and in the Scanning Electron Microscope (SEM). Association constant K(g) and K(e) were determined by the enhancement of the fluorescence of rhodamine 6G in the presence of Hβ-CD. Fluorescence of Rh6G is generally enhanced, in complexes of Rh6G and β-Cyclodextrin in aqueous solutions. The free energy change for the ground state (ΔG(g)) and for the excited state (ΔG(e)) have also been determined. The experimental results indicated that the inclusion process is an exothermic and spontaneous.     

Cyclodextrin-surfactant coassembly depends on the cyclodextrin ability to crystallize

Full equilibrium phase diagrams are presented for two ternary systems composed of the cationic surfactant dodecyltrimethylammonium bromide (DTAB), water (D(2)O), and a cyclodextrin, either β-cyclodextrin (β-CD) or (2-hydroypropyl)-β-cyclodextrin (2HPβCD). (2)H NMR, SAXS, WAXS, and visual examination were used to determine the phase boundaries and characterize the nature of the phases formed. Additionally, diffusion (1)H NMR was used to investigate parts of the diagrams. The water solubility of 2HPβCD is 80% (w/w), whereas it is only 1.85% (w/w) for β-CD. Solubility increases for both species upon complexation with DTAB; while the increase is minute for 2HPβCD, it is dramatic for β-CD. Both systems displayed an isotropic liquid solution (L(1)) one-phase region, the extension of which differs extensively between the two systems. Additionally, the DTAB:2HPβCD:water system also comprised a normal hexagonal (H(1)) area, which was not found for the DTAB:β-CD:water system. In the DTAB:β-CD:water system, on the other hand, we found cocrystallization of DTAB and β-CD. From this work we conclude that DTAB and CD molecules form 1:1 inclusion complexes with high affinities. Moreover, we observed indications of an association of 2HPβCD to DTAB micelles in the isotropic solution phase, which was not the case for β-CD and DTAB micelles. This is, to our knowledge, the first complete phase diagrams of surfactant-CD mixtures; as a novel feature it includes the observation of cocrystallization at high concentrations.     

Preparation and Spectroscopic Study of Different Stoichiometric Solid Supramolecular Inclusion Complexes of β-Cyclodextrin with Short Chain Aliphatic Amines

The solid Supramolecular complexes of β-cyclodextrin (β-CD) with ethylenediamine 1, diethylenetriamine 2 and triethylamine 3 were obtained and characterized using elemental analysis, powder X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, and 1H nuclear magnetic resonance spectroscopy. Based on the results of elemental analysis and 1H NMR, the guest-host stoichiometries of the three solid complexes were determined to be 5:2 for 1-β-CD, 1:1 for 2-β-CD, and 1:3 for 3-β-CD. The yields were relative to the molar volume ratio of guest toβ-CD cavity, and increased in the order: 1-β-CD<2-β-CD<3-β-CD. X-ray diffraction patterns of the inclusion complexes gave very good exhibitions not only in location of diffraction peaks but also in shape and diffraction intensity of the peaks due to the intermolecular complexations betweenβ-CD and the guests. The formation of host-guest inclusion complexes exhibited obviously enhanced phase change temperatures of the complexed guests such as 1 and 3. The H-5 protons located at the narrower rim inside the CD cavity experienced a higher shift upon inclusion while all other protons experienced lower shifts.     

Synthesis of a β-cyclodextrin derivate and its molecular recognition behavior on modified glassy carbon electrode by diazotization

A novel β-cyclodextrin (β-CD) derivative containing mono-phenylamino (MPA-β-CD) was newly synthesized by classical Mitsunobu reaction in good yield, and its structure has been confirmed by ¹H NMR, ¹³C NMR and electrospray ionization mass spectra. The compound MPA-β-CD was immobilized onto glassy carbon electrode (GCE) by diazotization, and with this modified electrode the binding behavior of MPA-β-CD for ferrocene (Fc) was investigated qualitatively, and the comparison of differential pulse voltammetry before and after immersion in ferrocene solution indicated that the MPA-β-CD immobilized GCE exhibited the molecular recognition behavior between β-CD and ferrocene.     

Preparation, characterization and pharmacodynamic activity of supramolecular and colloidal systems of rosuvastatin–cyclodextrin complexes

In the present study influence of nature of selected cyclodextrins (CDs) and of methods of preparation of drug–CD complexes on the oral bioavailability, in vitro dissolution studies and pharmacodynamic activity of a sparingly water soluble drug rosuvastatin (RVS) was investigated. Phase solubility studies were conducted to find the interaction of RVS with β-CD and its derivatives, which indicated the formation of 1:1 stoichiometric inclusion complex. The apparent stability constant (K_1:1) calculated from phase solubility diagram were in the rank order of β-CD < hydroxypropyl-β-cyclodextrin (HP-β-CD) < randomly methylated-β-cyclodextrin (RM-β-CD). Equimolar drug–CD solid complexes prepared by different methods were characterized by the Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). FTIR study demonstrated the presence of intermolecular hydrogen bonds and ordering of the molecule between RVS and CDs in inclusion complexes. DSC and XRD analysis confirmed formation of inclusion complex by freeze dried method with HP-β-CD and RM-β-CD. Aqueous solubility and dissolution studies indicated improved dissolution rates of prepared complexes in comparison with drug alone. Moreover, CD complexes demonstrated of significant improvement in reducing total cholesterol and triglycerides levels as compared to pure drug. However the in vivo results only partially agreed with those obtained from phase solubility studies.