Inclusion complexes of fluorofenidone with β-cyclodextrin and hydroxypropyl-β-cyclodextrin

Background: Fluorofenidone is a novel antifibrotic drug and its aqueous solubility is low. Aim: This study was to prepare and characterize inclusion complexes of fluorofenidone (AKF-PD) with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Method: The AKF-PD/cyclodextrins (CDs) inclusion complexes were prepared by coprecipitation and freeze-drying, respectively. The solubility enhancement of AKF-PD was evaluated by phase solubility method. Inclusion complexation in solid phase was studied by X-ray diffraction (XRD) and differential thermal analysis (DTA). The dissolution profiles of AKF-PD/CDs inclusion complexes were investigated and compared with those of their physical mixtures and AKF-PD alone. Results: The phase solubility diagrams of AKF-PD with β-CD and HP-β-CD were of A_L-types, and the solubility of AKF-PD could be increased by 51.5% for β-CD at 0.014 M and 794.0% for HP-β-CD at 0.254 M. The results from XRD and DTA suggested that AKF-PD could form inclusion complex with β-CD or HP-β-CD. The dissolution rate of AKF-PD from the inclusion complexes was much more rapid than AKF-PD alone. Conclusions: The formulation of AKF-PD/CDs inclusion complexes showed superior performance in improving dissolution properties of AKF-PD.     

The Solubilities of Esters of 4-Hydroxybenzoic Acid,Determined Separately and Together,in Aqueous Solutions of 2-Hydroxypropyl-β-cyclodextrin

Abstract

The solubilities of four esters of 4-hydroxybenzoic acid have been investigated singly and together in water and in aqueous solutions of 2-hydroxypropyl-β-cyclodextrin (HPCD). Values obtained for the solubilities of methyl (MP), ethyl (EP), propyl (PP), and butyl (BP) esters in water agreed welt with literature values, when determined separately. When measured together the solubilities of the methyl and butyl esters increased slightly, that of the ethyl ester decreased slightly, and the solubility of the propyl ester decreased by approximately 50%. Association constants for complexes of esters and HPCD determined separately in water agreed well with literature values, declining from methyl to ethyl and then increasing through propyl to butyl. When the association constants were determined for the esters together in solutions of HPCD the same pattern was noted, but the large decreases in association constants may indicate some other process in addition to competition between the esters for the HPCD molecules.     

The Effect of 2-Hydroxypropyl-β-cyclodextrin on In Vitro Drug Release of Steroids from Suppository Bases

The effects of 2-hydroxypropyl-β-cyclodextrin (HPCD) on drug solubility and drug release from suppository bases were studied for dexamethasone (DX), dexamethasone acetate (DXA), hydrocortisone (HC), hydrocortisone acetate (HCA), and prednisolone acetate (PNA). It was found that HPCD significantly increased the aqueous solubility of all five steroids, and the increased drug solubility significantly influenced the drug release from the polyethylene glycol (PEG) base but not from the cocoa butter base.     

Preparation and stability of iodine/α-cyclodextrin inclusion complex

Abstract

Inclusion complexes of iodine and α-cyclodextrin were prepared using the coprecipitation method. The complexes obtained were characterized in their solid state using differential scanning calorimetry and in their liquid phase using spectrophotometry, titrimetry and electrochemistry assays. The inclusion and preparation yields were determined. The 1:1 stoichiometry ratio of the inclusion compound was estimated on the basis of the inclusion yield. After optimization of the parameters of the laboratory assays, a scale-up experiment for the complex preparation was carried out. Stability studies showed that, after 16 months preservation, the inclusion complex remained quite stable and suitable for industrial scale-up according to a number of conditions.     

The Influence of 2-Hydroxypropyl-β-Cyclodextrin on Diffusion Rates and Transdermal Delivery of Hydrocortisone

Abstract

The influence of 2-hydroxypropyl-β-cyclodextrin (HPβCD) on the permeability of hydrocortisone through semi-permeable cellophane membrane and hairless mouse skin was investigated. When the hydrocortisone concentration was kept constant and the HPβCD concentration in an aqueous vehicle was gradually increased the flux through the semi-permeable membrane was increased until all hydrocortisone had dissolved, after that the flux decreased with increasing HPβCD concentration. A maximum flux was obtained when just enough HPβCD was used to dissolve all the drug in the aqueous vehicle.     

Inclusion complexation of 2-aminopyrimidines with β-cyclodextrin,physico-chemical and nuclear magnetic spectroscopic studies

Inclusion complexation of 2-aminopyrimidines with β-cyclodextrin was studied in the solid state by infrared spectroscopy (IR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The aminopyrimidine-β-CD complexes were also investigated in a solution by nuclear magnetic resonance spectral techniques (¹H-NMR and ¹³C-NMR). Qualitative modifications in the position and number of peaks or bands obtained from spectral methods as well as thermal analysis indicated the inclusion.     

Enhancement of dissolution rate and bioavailability of sulfamethoxazole by complexation with β-cyclodextrin

The purpose of this study was to improve the solubility and dissolution rate of sulfamethoxazole (SMZ) with inclusion compound of β-cyclodextrin (β-CD). The interaction between SMZ and β-CD in solution was studied by the phase-solubility method. The phase-solubility studies revealed the formation of inclusion complexes with poor solubility with an inclusion complex of 1:1 molar ratio and a stability constant of 122.3?M(-1). The solid complexes of SMZ with β-CD were prepared by using kneading and coprecipitation methods. The physical mixture of these chemicals was also prepared for comparison. Inclusion complexation was confirmed by the results from the studies of infrared spectoroscopy (IR) and differential scanning calorimetry (DSC). The effect of water-soluble polymers i.e., polyethylene glycol 20000 and non-ionic surfactants i.e., polysorbate 20 on the complexation of SMZ with β-CD was also investigated by the same methods. The rates of release of the active material from the complexes were determined from dissolution studies using USP XXII paddle method. The formulation, that provided delivery of active material near to the target value in six healthy volunteers and in vivo tests, clearly revealed that the bioavailability of active material was found to be enhanced by preparing ternary mixtures.     

Host–guest inclusion system of mangiferin with β-cyclodextrin and its derivatives

The characterization, inclusion complexation behavior and binding ability of the inclusion complexes of mangiferin (MGF) with β-cyclodextrin and its derivatives (hydroxypropyl-β-cyclodextrin (HPβCD), sulfobutyl ether β-cyclodextrin (SBEβCD) and mono (6-ethylene-diamino-6-deoxy)-β-cyclodextrin (ENβCD)) were investigated in both solution and solid state by means of PL spectroscopy, ¹H and 2D NMR, XRD, TG and DSC. The results showed that the water solubility and thermal stability of MGF were significantly increased in the inclusion complex with cyclodextrins. The MGF/CDs complexes will be potentially useful for the design of a novel formulation of mangiferin for herbal medicine.     

Dissolution enhancement of cefdinir with hydroxypropyl-β-cyclodextrin

The solid state properties and dissolution behavior of binary systems of cefdinir (CEF) with hydroxypropyl-β-cyclodextrin (HP-β-CD) were investigated. CEF-HP-β-CD interaction in the solution state was studied by phase-solubility analysis and demonstrates the ability of HP-β-CD to complex with CEF giving A_L type profile with 65.28?±?1.3?M^?1 stability constant. The freeze drying technique was adopted to prepare binary systems of CEF with HP-β-CD in 1:1 molar ratio. The solid inclusion was characterized by fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRD), and scanning electron microscopy (SEM). Aqueous solubility of CEF-HP-β-CD inclusion complex was 2.36-fold of pure CEF. The dissolution profiles of inclusion complexes were determined and compared with those of CEF alone and their physical mixtures. The dissolution rate of inclusion complex was superior than the CEF alone. These approaches indicated that CEF was able to form an inclusion complex with HP-β-CD, and the inclusion compounds exhibited different spectroscopic features and properties.     

Activity Interaction Coefficients of Si in Cu-Ti-Si Melts at 1550℃

Activitibs of Si in binary Cu-Si and ternary Cu-Ti-Si melts were measured at 1 550℃ by using a method of chemical equilIbrium between gas and liquid. The activity interaction coefficients of Si in the melts have been determined from the experimental data (lny = -5.69. s = 6.69. P2: = -26.22. E; =-43.96) and activity interaction coefficients of Ti in binary Cu-Ti melt at 1550℃ has been estimated from Sommer's data based on the regular solution model (lny =-1 .10. : = 2.95.p:=-2.10).     

Characterization and In Vivo Evaluation of an Inclusion Complex of Oridonin and 2-hydroxypropyl-β-cyclodextrin

Oridonin, a diterpenoid, is a sparingly soluble compound and its aqueous solubility can't meet the requirement of clinical intravenous administration. This study was, accordingly, to prepare an inclusion complex of oridonin and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) by lyophilization to improve its apparent solubility. The solubility enhancement of oridonin was evaluated by phase solubility method, and the phase solubility curve displayed a typical A_L-type, indicating the formation of 1:1 inclusion complex. The formation of inclusion complex was confirmed by DSC, XRD, FTIR, and NMR, and thereby two possible inclusion modes were inferred. In vivo studies demonstrated that HP-β-CD had no significant effect on the plasma pharmacokinetic behaviors of oridonin following i.v. administration to rats, but the inclusion complex tended to decrease the distribution of oridonin in heart, spleen, and kidney and increase that in lung in mice, compared to that of free drug.     

Thermochemical processing with hydrogen of super-α2 alloy

Thermochemical processing (TCP) with hydrogen, including hydrogenation, intermediate heat treatment and dehydrogenation, of super-₂, a type of Ti₃Al-based titanium aluminide alloy, was carried out in order to examine the microstructural variations in the alloy. It is shown that a number of microstructural changes, such as the amount, morphology and distribution of different phases in the alloy, can be brought about by TCP. Acicular or Widmanstatten ₂ was found to form in the retained B2 matrix under TCP with an intermediate heat treatment of furnace cooling from high temperature, instead of mainly equiaxed ₂ under the normal treatment. The precipitation in the microstructures for alloys undergoing TCP with the intermediate -solution heat treatment followed by ageing while dehydrogenating was found to be more regular in morphology and homogeneous in distribution. Both the amount of primary ₂ and the size of the primary grains in the microstructure could be controlled by suitable TCP. Some of the reasons leading to the microstructural variations caused by TCP are discussed.     

Interaction of Water with GeCl4 , SnCl4 , and AsCl3

The interaction of water with GeCl₄, SnCl₄, and AsCl₃ was studied by IR spectroscopy. The results demonstrate that these chlorides contain molecular water in monomeric form. At water concentrations above 10^–2 mol/l, GeCl₄ also contains H₃O⁺ ions. The mechanisms of GeCl₄ and AsCl₃ hydrolysis were studied over a wide range of water concentrations.     

Synthesis of α-Mo_2C by Carburization of α-MoO_3 Nanowires and Its Electrocatalytic Activity towards Tri-iodide Reduction for Dye-Sensitized Solar Cells

Nanowire-shaped α-Mo O3 was synthesized on a large scale by hydrothermal route.Nanocrystalline α-Mo2 C phase was obtained by the carburization of α-Mo O3 nanowires with urea as a carbon source precursor.The phase purity and crystalline size of the synthesized materials were ascertained by using powder X-ray diffraction.The shape and morphology of synthesized materials were characterized by field-emission scanning electron microscopy(FE-SEM) and high resolution transmission electron microscopy(HR-TEM).The electrocatalytic activity of α-Mo2 C for I-/I3-redox couple was investigated by the cyclic voltammetry.The synthesized α-Mo2 C was subsequently applied as counter electrode in dye-sensitized solar cells to replace the expensive platinum.     

Interactions between preservatives and 2-hydroxypropyl-β-cyclodextrin

Abstract

The interactions between several commonly used preservatives, i.e. benzalkonium chloride, chlorhexidine gluconate, chlorobutanol, methylparaben and propylparaben, and 2-hydroxypropyl-β-cyclodextrin were investigated. The interactions were shown to be twofold. Firstly, the preservative molecules can displace the drug molecules from the cyclodextrin cavity, thus, reducing the solubilizing effects of the cyclodextrin. Secondly, the antimicrobial activity of the preservatives were reduced by formation of preservative-cyclodextrin inclusion complexes. The magnitude of the interactions were dependent on the degree of complexation.     

Enhanced solubility and dissolution rate of amiodarone by complexation with β-cyclodextrin through different methods

The aim of this work was to investigate the inclusion complexation between amiodarone (AMD), a practically water insoluble anti arrhythmic agent, and β-cyclodextrin (βCD) in order to improve the solubility and the dissolution rate of the drug, in an attempt to enhance its bioavailability. The complexation was done through different methods: physical mixture (PM), coevaporated (CV), freeze-drying (FD) and spray-drying (SD). The data analysis indicated that the complexes produced by freeze-drying and spray-drying techniques resulted in amorphous samples (data obtained by DSC and XRPD), and showed a possible chemical interaction between OH-βCD group and AMD tertiary amine (visualized by FT-IR). Also, they presented higher thermal stability (demonstrated by TG) and the improvement of the drug dissolution rate.     

Interaction of furans and thiophenes with Cu (II) — exchanged ZSM-5 and Y zeolites

The formation of radicals on furan and thiophene and their methyl derivatives of CuZSM-5 and on CuY zeolites was studied by EPR technique. In some cases, stable monomer radicals of furans and thiophenes were observed on CuZSM-5, whereas the dimeric radicals were observed mainly on CuY. The channel structure of the zeolite seemed to affect the formation of radical species.     

Low Temperature Synthesis of TiO2 Nanoparticles with High Photocatalytic Activity and Photoelectrochemical Properties through Sol–Gel Method

In the present work TiO₂ nanoparticles were prepared by sol–gel method and both small-sized nanoparticles and proper crystals were delivered by simultaneous use of surfactant, which was applied for the purpose of size reduction of nanoparticles, and acid ions that were used so that the formation of crystalline structures occurs appropriately. Photocatalytic activity of samples was measured by degrading RO dye, and photoelectrochemical properties were assayed using anodic photocurrent responses under Xe lamp light irradiation. The synthesized nanoparticles exhibit great photoelectrochemical and photocatalytic activity compared to that of commercial photocatalyst, Degussa P-25, which demonstrates that the method can be applied in the synthesis of other semiconductor oxides nanoparticles.     

Solubility and dissolution rate improvement of the inclusion complex of apigenin with 2-hydroxypropyl-β-cyclodextrin prepared using the liquid antisolvent precipitation and solvent removal combination methods

Apigenin (AP) has many pharmacological activities. AP has poor solubility in some solvents. AP is insoluble in water and slightly soluble in ethanol (1.93?mg/ml). It has limited application and exploitation. Therefore, the liquid antisolvent precipitation (LAP) method was applied to improve the solubility of AP in ethanol by changing its crystal form or producing ultra-fine particles. Then, the inclusion complex of AP with 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) is prepared using the solvent removal method. The effects of various experimental parameters on the solubility of AP in ethanol were investigated through the single factor design. Under the optimum conditions, the AP–ethanol solution of 6.19?mg/ml was obtained. The inclusion complex of AP with HP-β-CD was obtained by the solvent removal method. The load efficiency (LE) and drug encapsulation efficiency (EE) of the inclusion complex of AP with HP-β-CD were 13.98%±0.14% and 97.86%±1.07%, respectively. SEM, FTIR, ¹HNMR, XRD, DSC and TG were used to analyze the characteristics of the inclusion complex of AP with HP-β-CD. These results showed that the inclusion complex has significantly different characteristics with AP. In addition, the dissolution rate and solubility of the inclusion complex were approximately 15.24 and 68.7 times higher than AP in artificial gastric juice, and was separately 10.4 times and 40.05 times higher than AP in artificial intestinal juice. The bioavailability of inclusion complex increased 3.97 times compared with AP.