Inclusion complex of usnic acid with β-cyclodextrin: characterization and nanoencapsulation into liposomes

In this study β-cyclodextrin (β-CD) was used to improve usnic acid (UA) solubility and the inclusion complex (UA:β-CD) was incorporated into liposomes in order to produce a targeted drug delivery system for exploiting the antimycobacterial activity of UA. A phase-solubility assay of UA in β-CD at pH 7.4 was performed. An apparent stability constant of K_1:1 = 234.5 M^?1 and a complexation efficiency of 0.005 was calculated. In the presence of 16 mM of β-CD the solubility of UA (7.3 μg/mL) increased more than 5-fold. The UA:β-CD complex was prepared using the freeze-drying technique and characterized through infrared and ¹HNMR spectroscopy, X-ray diffraction and thermal analyses. The UA:β-CD inclusion complex presented IR spectral modifications when compared with UA and β-CD spectra. ¹HNMR spectrum of UA:β-CD inclusion complex showed significant chemical shifts in proton H5 located inside the cavity of β-CD (Δδ = 0.127 ppm), suggesting that phenyl ring moiety of UA would be expected to be included within the β-CD cavity, interacting with the H-5 proton. A change in UA from its crystalline to amorphous form was observed on X-ray, suggesting the formation of a drug inclusion complex. DSC analysis showed the disappearance of the UA fusion peak UA:βCD complex. No differences between the antimicrobial activity of free UA and UA:βCD were found, supporting the hypothesis that the complexation with cyclodextrin did not interfere with drug activity. Liposomes containing UA:βCD were prepared using hydration of a thin lipid film method with subsequent sonication. Formulations of liposomes containing UA:βCD exhibited a drug encapsulation efficiency of 99.5% and remained stable for four months in a suspension form. Interestingly, the encapsulation of UA:βCD into the liposomes resulted in a modulation of in vitro kinetics of release of UA. Indeed, liposomes containing UA:β-CD presented a more prolonged release profile of free usnic acid compared to usnic acid-loaded liposomes.     

Inclusion complexes of cyclodextrins with 4-amino-1,8-naphthalimides (part 2)

Fluorescence spectroscopy was used to characterize inclusion compounds between 4-amino-1,8-naphthalimides (ANI) derivatives and different cyclodextrins (CDs). The ANI derivatives employed were N-(12-aminododecyl)-4-amino-1,8-naphthalimide (mono-C₁₂ANI) and N,N′-(1,12-dodecanediyl)bis-4-amino-1,8-naphthalimide (bis-C₁₂ANI). The CDs used here were α-CD, β-CD, γ-CD, HP-α-CD, HP-β-CD and HP-γ-CD. The presence of CDs resulted in pronounced blue-shifts in the emission spectra of the ANI derivatives, with increases in emission intensity. This behavior was parallel to that observed for the dyes in apolar solvents, indicating that inclusion complexes were formed between the ANI and the CDs. Mono-C₁₂ANI formed inclusion complexes of 1:1 stoichiometry with all the CDs studied. Complexes with the larger CDs (HP-β-CD, HP-γ-CD and γ-CD) were formed by inclusion of the chromophoric ANI ring system, whereas the smaller CDs (α-CD, HP-α-CD and β-CD) formed complexes with mono-C₁₂ANI by inclusion of the dodecyl chain. Bis-C₁₂ANI formed inclusion complexes of 1:2 stoichiometry with HP-β-CD, HP-γ-CD and γ-CD, but did not form inclusion complexes with α-CD, HP-α-CD and β-CD. The data were treated in the case of the large CDs using a Benesi-Hildebrand like equation, giving the following equilibrium constants: mono-C₁₂ANI:HP-β-CD (K ₁₁ = 50 M^?1), mono-C₁₂ANI:HP-γ-CD (K ₁₁ = 180 M^?1), bis-C₁₂ANI:HP-β-CD (K ₁₂ = 146 M^?2), bis-C₁₂ANI:HP-γ-CD (K ₁₂ = 280 M^?2).     

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

Complexation between sulconazole (SULC), an imidazole derivative with in vitro antifungal and antiyeast activity, and β-cyclodextrins (β-CD and HP-β-CD) was studied in solution and in solid states. Complexation in solution was evaluated using solubility studies and nuclear magnetic resonance spectroscopy (¹H-NMR). In the solid state, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and RX diffraction studies were used. Solubility studies suggested the existence of inclusion complex between SULC and β-CD or HP-β-CD. ¹H-NMR spectroscopy studies showed that the complex formed occurs by complexation of imidazole ring into inner cavity. DSC studies showed the existence of a complex of SULC with β-CD. The TGA and RX studies confirmed the DSC results of the complex. Solubility of SULC in solid complexes was studied by the dissolution method and it was found to be much more soluble than the uncomplexed drug.     

NMR studies of interactions of new CB2 cannabinoid receptor ligands with cyclodextrins hosts. Correlation with micellar electrokinetic chromatography and reversed phase high performance liquid chromatography

Three selective CB₂ cannabinoid receptor ligands have recently been discovered to be promising anti-inflammatory agents but their low water solubility hinder their per os administration. The popularity of the cyclodextrins, from a pharmaceutical standpoint lies on their ability to interact with poorly water-soluble drugs and improve their solubility. Herein, three experimental approaches for calculating the stability constant of complexes between the selective CB₂ ligands and either the β-CD or the HP-β-CD, were tested: nuclear magnetic resonance, micellar electrokinetic chromatography and high performance liquid chromatography in reversed phase. In NMR studies the calculated K values were relatively high and were between 1486 and 3571 M^?1 with β-CD. With HP-β-CD they were between 1203 and 2650 M^?1. Concerning the two others techniques the K values were found lower. In MECK studies with β-CD they were between 308 and 792 M^?1 and with HP-β-CD between 124 and 764 M^?1. Finally in RP-HPLC studies with β-CD, they were between 539 and 1144 M^?1 and with HP-β-CD between 196 and 396 M^?1. These calculated constants suggest that a complexation phenomenon occurs. A model for inclusion of one of the CB₂ ligands in the β-CD was then proposed from molecular modeling studies.     

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.     

Complexation of ebastine with β-cyclodextrin derivatives

Complexation of ebastine (EB) with hydroxypropyl and methyl-β-cyclodextrin (HP-β-CD and Me-β-CD) was studied in aqueous solutions and in the solid state. The formation of inclusion complexes in aqueous solutions was analysed by the solubility method. The assays were designed using low CD concentrations compared with the solubility of these derivatives in order to avoid non-inclusion phenomena and to obtain a linear increase in EB solubility as a function of CD concentration. The values of complexation efficiency for HP-β-CD and Me-β-CD were 1.9 × 10^?2 and 2.1 × 10^?2, respectively. It seems that the non polar character of the methyl moiety slightly favoured complexation. In relation to solid state complexation, 1:1 EB:CD systems were prepared by kneading, and by heating a drug-CD mixture at 90 ºC. They were analysed using X ray diffraction analysis by comparison with their respective physical mixtures. A complex with a characteristic diffraction pattern similar to that of the channel structure of β-CD was formed with Me-β-CD in 1:1 melted and 1:2 EB:CD kneaded systems. Complexation with HP-β-CD was not clearly evidenced because only a slight reduction of drug crystallinity was detected. Finally, the loading of EB in two β-CD polymers cross-linked with epichlorohydrin yielded 7.3 and 7.7 mg of EB/g polymer respectively.     

Thermodynamic study of inclusion complexes of zaleplon with natural and modified cyclodextrins

The thermodynamics and stoichiometry of zaleplon (ZAL) complexation with different cyclodextrin derivatives [β-CD, hydroxypropyl-β-cyclodextrin (HP-β-CD), randomly methylated-β-cyclodextrin (RAMEB), sulphobutylether-β-cyclodextrin (SBE-β-CD)] in aqueous solution was studied by spectrofluorimetry and ¹H NMR spectroscopy in order to obtain a more general understanding of the driving forces behind the inclusion phenomena. Job’s plot derived from the NMR spectral data and statistical analysis of spectrofluorimetric titration data confirmed the formation of equimolar complexes in all systems tested, excluding the possibility of higher order complex formation. Furthermore, thermodynamic parameters obtained by both techniques gave similar and negative values of ΔG° for all complexes, indicating spontaneous inclusion of drug into CDs. From a thermodynamic point of view, two types of inclusions were determined. One is enthalpy driven ZAL complexation with β-CD, HP-β-CD and RAMEB, while the other is entropy driven complexation observed in the case of SBE-β-CD. The mechanisms behind each type of inclusion were discussed in detail.     

Effect of hydroxypropyl-β-cyclodextrin complexation on the aqueous solubility, structure, thermal stability, antioxidant activity, and tyrosinase inhibition of paeonol

The objective of this paper is to study the effect of hydroxypropyl-β-cyclodextrin (HP-β-CD) complexation on the aqueous solubility, structure, thermal stability, antioxidant activity, and tyrosinase inhibition of paeonol (PAE). The inclusion complex (PAE-HP-β-CD complex) of HP-β-CD and PAE was prepared by a freeze-drying method. Phase solubility tests showed that the stability constant of the inclusion complex was about 33.8?M^?1 at 25?°C. The experimental results of proton nuclear magnetic resonance (H-NMR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) suggested that PAE was included by HP-β-CD to form the PAE-HP-β-CD complex. Furthermore, the thermogravimetric analysis (TGA) results showed that the thermal stability of PAE was improved when it was complexed with HP-β-CD. Comparing the antioxidant activity of PAE with that of the PAE-HP-β-CD complex at the same concentration revealed that the complex of PAE with HP-β-CD was better able to eliminate radical. Furthermore, the experimental results revealed that the formation of a complex with HP-β-CD increased the water solubility of PAE, improving its apparent inhibitive activity of tyrosinase.     

Study on the inclusion interaction of ethyl violet with cyclodextrins by MWNTs/Nafion modified glassy carbon electrode

The interactions of ethyl violet (EV) with cyclodextrins (CDs) were investigated by Multi-wall carbon nanotubes/Nafion composite film modified glassy carbon electrode (MWNTs/Nafion/GCE). It was found that the MWNTs/Nafion composite film can effectively catalyze the electrode reaction of EV. The variation of the electrochemical behavior of EV upon the addition of CDs indicated the formation of the inclusion complexes of EV with β-CD, heptakis (2,3,6-tri-O-methyl)-β-CD (TM-β-CD), heptakis (2,6-di-O-methyl)-β-CD (DM-β-CD), hydroxypropyl-β-CD (HP-β-CD), and carboxymethyl-β-CD (CM-β-CD). The stoichiometry ratios of EV and the above five CDs were found to be 1:1. The inclusion ability obeyed the order: CM-β-CD > HP-β-CD > TM-β-CD > DM-β-CD > β-CD. The results showed that the modified β-CDs exhibited stronger binding ability than native β-CD, especially the charged CM-β-CD, which implied that the inclusion capacity depends on not only size matching and hydrophobicity but also electrostatic interaction. ¹HNMR spectra and molecule mechanics calculations suggested that EV was included into the cavity of β-CD from the wider side.     

Naproxen: Hydroxypropyl-β-Cyclodextrin:Polyvinylpyrrolidone Ternary Complex Formation

The aim of the present study was to investigate the effect of the presence of thewater-soluble polymer polyvinylpyrrolidone (PVP) MW = 24000 g/mol, on thecomplexation of the phototoxic anti-inflammatory drug naproxen, in its sodiumsalt form, with hydroxypropil-β-cyclodextrin (HP-β-CD). The datashown that the polymer interacts with the free naproxen and with thenaproxen:HP-β-CD inclusion complex. The presence of different proportions of PVP, in the 0–1%(w/w) rangesystematically increased the K_app of the naproxen:HP-β-CD inclusioncomplex formation. The cause of this increase is that the polymer interactswith the HP-β-CD with a binding constant of K₂ = 29000 ± 53 M^-1; and with the naproxen:HP-β-CD inclusion complex, to givea ternary complex naproxen:HP-β-CD:PVP. The binding constant of thisprocess was K₃ = 5350 ± 1 M^-1. NMR data revealed that in the ternary system, PVP is outside of the cyclodextrin, and therefore must be wholly or partially recovering the naproxen:HP-β-CD inclusion complex.     

Enhancement inhibition efficiency of PBTCA depending on the inclusion complex with hydroxypropyl-β-cyclodextrin

For the first time, hydroxypropyl-β-cyclodextrin (HP-β-CD) has been brought in to include 2-phosphonobutane-1,2,4-tricarboxylic acid (PBTCA) in order to enhance inhibition efficiency of PBTCA, which leads a new approach to study oil–gas field corrosion inhibition in the process of acid treatment. Based on the host–guest inclusion reaction, the inclusion complex of PBTCA with HP-β-CD has been prepared in the laboratory. UV–Vis absorption spectrum was applied to study the inclusion behavior of PBTCA with HP-β-CD. The results revealed that PBTCA with HP-β-CD can form a 1:1 stoichiometry inclusion complex. The 1:1 inclusion complex synthesized by using lyophilization was further characterized by Fourier transform infrared spectroscopy. Besides, inhibition effect of the inclusion complex on the corrosion inhibition of Q235 carbon steel has been investigated in 0.1 M sulfuric acid (H₂SO₄) solution using potentiodynamic polarization, electrochemical impedance spectroscopy techniques and scanning electron microscopy (SEM). It was found that the presence of the inclusion complex better achieved the anti-corrosion property in aggressive medium than was the case with alone PBTCA and the highest inhibition efficiency of the inclusion complex over 90 % was obtained, which are suggestive of the active effect of the inclusion complex for improving inhibition efficiency of PBTCA. Meanwhile, the results obtained from SEM further showed that the inclusion complex acts as a more efficient corrosion inhibitor for Q235 carbon steel in H₂SO₄ medium.     

Comparison between 2-hydroxypropyl-��-cyclodextrin and 2-hydroxypropyl-��-cyclodextrin for inclusion complex formation with danazol

Complexation in solution between danazol and two different cyclodextrins [2-hydroxypropyl-??-cyclodextrin (HP-??-CD) and 2-hydroxypropyl-??-cyclodextrin (HP-??-CD)] was studied using phase solubility analysis, and one- and two-dimensional ¹H-NMR. The increase of danazol solubility in the aqueous cyclodextrin solutions showed a linear relationship (A_L profile). The apparent stability constant, K _1:1, of each complex was calculated and found to be 51.7 × 10³ and 7.3 × 10³ M^?1 for danazol?CHP-??-CD and danazol?CHP-??-CD, respectively. ¹H-NMR spectroscopic analysis of varying ratios of danazol and the different cyclodextrins in a mixture of EtOD?CD₂O confirmed the 1:1 stoichiometry. Cross-peaks, from 2D ROESY ¹H-NMR spectra, between protons of danazol and H3?? and H5??of cyclodextrins, which stay inside the cyclodextrin cavity, proved the formation of an inclusion complex between danazol and the cyclodextrins. For HP-??-CD, the inclusion complex is formed by entrance of the isooxazole and the A rings of danazol in the cyclodextrin cavity. For HP-??-CD, two different inclusion structures may exist simultaneously in solution: one with the isooxazole and A ring in the cavity and the other with the C and D ring inside the cavity. DLS showed that self-aggregation of the CD??s was absent in the danazol HP-??-CD system up to a CD concentration of 10% and in the danazol HP-??-CD system up to a CD concentration of 5%.     

Guest–Host Interactions between Crown-Containing 2-Styrylbenzothiazole and HP-β-CD

The inclusion complexes of the trans-isomer of2-[2-(6,7,9,10,12,13,15,16-octahydro-5,8,11,14,17-pentaoxa-benzocyclopentadecen-2-yl)-vinyl]-benzothiazole(CSB) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) were investigatedby electronic absorption and fluorescence spectroscopies in aqueous solution. Theaddition of HP-β-CD has very little effect on the absorption spectra of CSB.A 17-nm blue shift and pronounced fluorescence enhancements in the emissionspectrum of CSB were observed. 1:1 and 1:2 stoichiometries were found forcomplexes of CSB with HP-β-CD, and formation constants of the complexesand other thermodynamic parameters were estimated from fluorescence measurements.In the case of the 1:1 CSB: HP-β-CD complex, the formation constant was equalto 3,802 at 293 K, the complexation reaction was exothermic (Δ H⁰ = -9.2 ±1.1 kJ mol^-1) and presented a positive entropy value (Δ S⁰ = 37.3 ± 3.8 Jmol^-1 K^-1). A molecular structure was proposed for the CSB:HP-beta;-CDinclusion complex.     

Photoinduced protonation and mechanical motion in the cyclodextrin cavity: Synthesis,structure and spectral properties of 4-(2-napthyl)pyridine and their pseudorotaxane complexes

The spontaneous and photoinduced protonation of 4-(2-naphthyl)pyridine (1) in solutions and in complexes with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) were studied by absorption and fluorescence spectroscopy. The structure and stability of the complexes (log K = 1.5–2.3) of 1, its protonated form 2, and quaternized derivative, 1-methyl-4-(2-naphthyl)pyridinium perchlorate (3), with β-CD and HP-β-CD were studied by ¹H NMR. It was shown that irrespective of the solution pH, compound 1 resides in the cyclodextrin cavity. HP-β-CD better binds the neutral form of 1 than β-CD, while naphthylpyridinium salts have approximately equal binding affinity to both cyclodextrins. The structures of salt 3 and pseudorotaxane complex 1@β-CD were determined by X-ray diffraction analysis. According to spectral data, pK_a of 1 in water is 5.12, which promotes protonation of nitrogen both in the ground state and in the excited state. As a consequence, the fluorescence spectrum exhibits only the protonated form with a lifetime of 15 ns. The addition of HP-β-CD to a solution of 1 results in inclusion complex 1@HP-β-CD; simultaneously pK_a of 1 decreases to 4.62 and non-protonated form fluorescence (NFF) of 1 with a lifetime of 1.25 ns appears. Thus, the residence of 1 in the HP-β-CD cavity hampers its protonation in the excited state. From comparison of the initial regions of fluorescence of 1 in solution and in the HP-β-CD complex after pulse excitation, a mechanism for appearance of short-lived NFF of 1 was proposed. Quantum chemical simulation of the protonation and complexation of 1 in the presence of water was performed. On the basis of results, reversible photoinduced mechanical motion of 1 in the HP-β-CD cavity was suggested.     

Host–guest system of 4-nerolidylcatechol in 2-hydroxypropyl-β-cyclodextrin: preparation, characterization and molecular modeling

The interaction of 4-nerolidylcatechol (4-NRC), a potent antioxidant agent, and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated by the solubility method using Fourier transform infrared (FTIR) methods in addition to UV–Vis, ¹H-nuclear magnetic resonance (NMR) spectroscopy and molecular modeling. The inclusion complexes were prepared using grinding, kneading and freeze-drying methods. According to phase solubility studies in water a B_S-type diagram was found, displaying a stoichiometry complexation of 2:1 (drug:host) and stability constant of 6494 ± 837 M^?1. Stoichiometry was established by the UV spectrophotometer using Job’s plot method and, also confirmed by molecular modeling. Data from ¹H-NMR, and FTIR, experiments also provided formation evidence of an inclusion complex between 4-NRC and HP-β-CD. 4-NRC complexation indeed led to higher drug solubility and stability which could probably be useful to improve its biological properties and make it available to oral administration and topical formulations.     

Minoxidil–2-hydroxypropyl-β-cyclodextrin inclusion complexes: characterization and in vivo evaluation of an aqueous solution for hair growth in rats

Minoxidil dissolved in organic solvents is commonly used in the treatment of androgenic alopecia because it is hydrophobic and poorly soluble in water. The aim of this investigation was to develop an aqueous minoxidil solution without addition of organic solvents. To this end, minoxidil was encapsulated in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to form a minoxidil–HP-β-CD inclusion complex with aqueous solubility higher than that of pure minoxidil. Minoxidil–HP-β-CD inclusion complexes were prepared using a freeze-drying method from minoxidil and HP-β-CD at a molar ratio of 1:1. Complex formation was confirmed by nuclear magnetic resonance, thermogravimetric analysis, and thin layer chromatography. The structure of the complex was determined using two-dimensional rotating frame overhauser effect spectroscopy. Minoxidil–HP-β-CD inclusion complexes were dissolved in water to form a homogeneous aqueous solution, and its effect on the hair cycle of mice was evaluated in vivo. The results support the feasibility of using HP-β-CD to prepare an aqueous minoxidil solution to replace organic solvent-based solutions.     

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.     

Thermodynamic approach for studying both the retention and complexation mechanisms with hydroxy-propyl-beta-cyclodextrin of a phenoxy-propionic acid herbicide series

The retention and complexation mechanisms of a herbicide series were studied from a chromatographic approach using a novel column called “Nautilus^®”. The effects of water fraction and the hydroxy-propyl-β-cyclodextrin (HP-β-CD) concentration in the mobile phase were analysed in relation to the column temperature. Two retention models of phenoxy-propionic acid (PPA) derivatives were investigated. It was shown that the retention mechanism was led by free PPA herbicide for low HP-β-CD concentrations and by the PPA/HP-β-CD complex for the highest ones. In addition, an enthalpy-entropy compensation study revealed that both the solute retention and complexation mechanisms were independent of the number of chlorine atoms in the structure. Also the thermodynamic results showed that (1) the retention process depended on the water fraction (X) in the mobile phase and (2) the PPA/HP-β-CD complexation mechanism was shown to be entropically controlled.     

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.     

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.