The physicochemical characteristics of freeze-dried scutellarin-cyclodextrin tetracomponent complexes

In an effort to improve the solubility of the insoluble drug scutellarin, a novel complexation of scutellarin with β-cyclodextrin (β-CD) was studied. Tetracomponent freeze-dried complex was prepared with scutellarin, β-CD, Hydroxypropyl Methylcellulose (HPMC), and triethanolamine. To confirm complex formation, complex was characterized by Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction, and differential scanning calorimetry (DSC). Phase-solubility analysis suggested the soluble complexes having 1:1 stoichiometry. The β-CD solubilization of scutellarin could be improved significantly by combining water-soluble polymer and pH adjuster. Comparing the binary, ternary solid systems with tetrary systems, tetracomponent freeze-dried complex showed the best effect of solubilization. A maximal solubility of scutellarin (23.65 mg/ml) was achieved with tetracomponent freeze-dried complex, up to 148-fold increase over scutellarin solubility in water, and the solubility of scutellarin is 15.35 ug/ml (up to 6-fold) in simulated gastric fluid.     

Effects of grinding with microcrystalline cellulose and cyclodextrins on the ketoprofen physicochemical properties

Ground mixtures of ketoprofen (KETO) with native crystalline β-cyclodextrin, amorphous statistically substituted methyl-β-cyclodextrin, and microcrystalline cellulose were investigated for both solid phase characterization (differential scanning calorimetry (DSC) powder X-ray diffractometry, and infrared (IR) spectrometry) and dissolution properties (dispersed amount and rotating disk methods) to evaluate the role of the carrier on the performance of the final product. The effects of different grinding conditions, partial sample dehydration, and 1 year storage at room temperature were also investigated. The results pointed out the importance of the carrier nature on the efficiency of the cogrinding process. Both cyclodextrins were much more effective than was microcrystalline cellulose, even though no true inclusion complex formation occurred by mechanochemical activation. The best results were obtained from ground mixtures with methyl-β-cyclodextrin, which showed the best amorphizing and solubilizing power toward the drug and permitted an increase of approximately 100 times its intrinsic dissolution rate constant, in comparison with the approximate 10 times increase obtained from ground mixtures with β-cyclodextrin.     

The influence of diluent on the release of theophylline from hydrophilic matrix tablets

The role of β-cyclodextrin (β-CD) on the apparent solubility of theophylline was investigated by the solubility method. Binary systems of theophylline and β-CD were prepared using the dry co-grinding method. Their characterization was performed by differential scanning calorimetry (DSC). The dissolution rate of theophylline and theophylline/β-CD and dissolution studies of matrix tablets prepared from mixtures containing theophylline and ground theophylline were carried out. It can be concluded that β-CD is related to an increase in the apparent solubility and dissolution rate of the drug, promoting improvement on the release of theophylline from matrices manufactured with hydroxypropylmethylcellulose (HPMC). This can be attributed to the amorphous state and the increased wettability of the drug.     

Development of fast-dissolving tablets of flurbiprofen-cyclodextrin complexes

The present study was aimed at developing a tablet formulation based on an effective flurbiprofen-cyclodextrin system, able to allow a rapid and complete dissolution of this practically insoluble drug. Three different cyclodextrins were evaluated: the parent β-cyclodextrin (previously found to be the best partner for the drug among the natural cyclodextrins), and two amorphous, highly soluble β-cyclodextrin derivatives, i.e., methyl-β-cyclodextrin and hydroxyethyl-β-cyclodextrin. Equimolar drug-cyclodextrin binary systems prepared according to five different techniques (physical mixing, kneading, sealed-heating, coevaporation, and colyophilization) were characterized by Differential Scanning Calorimetry, x-ray powder diffractometry, infrared spectroscopy, and optical microscopy and evaluated for solubility and dissolution rate properties. The drug solubility improvement obtained by the different binary systems varied from a minimum of 2.5 times up to a maximum of 120 times, depending on both the cyclodextrin type and the system preparation method. Selected binary systems were used for preparation of direct compression tablets with reduced drug dosage (50 mg). Chitosan and spray-dried lactose, alone or in mixture, were used as excipients. All formulations containing drug-cyclodextrin systems gave a higher drug dissolved amount than the corresponding ones with drug alone (also at a dose of 100 mg); however, the drug dissolution behavior was strongly influenced by formulation factors. For example, for the same drug-cyclodextrin product the time to dissolve 50% drug varied from less than 5 minutes to more than 60 minutes, depending on the excipient used for tableting. In particular, only tablets containing the drug kneaded with methyl-β-cyclodextrin or colyophilized with β-cyclodextrin and spray-dried lactose as the only excipient satisfied the requirements of the Food and Drug Administration (FDA) for rapid dissolving tablets, allowing more than 85% drug to be dissolved within 30 minutes. Finally, it can be reasonably expected that the obtained drug dissolution rate improvement will result in an increase of its bioavailability, with the possibility of reducing drug dosage and side effects.     

Cyclodextrin complex osmotic tablet for glipizide delivery

Poorly soluble glipizide was selected as the model drug to prepare osmotic pump tablets (OPT) with proper accessorial material after it was made an inclusion complex by kneading method in order to increase solubility. Polyethylene glycol 4000 (PEG4000) and cellulose acetate (CA) were selected as the coating materials, and acetone-water (95:5) co-solvent was employed as the coating medium. The effects of the osmotic promoting agent, diameter of the drug-releasing orifice, coating composition, and coat weight on the drug release profile were investigated. The drug release profile of the optimal formulation was compared with a commercialized push-pull osmotic tablet. The results indicated that glipizide-cyclodextrin inclusion complex OPT had excellent zero-order release characteristics in vitro.     

Ofloxacin/beta-cyclodextrin complexation

Ofloxacin (OFX) is a fluorquinolone characterized by photochemical instability. With the goal to improve its photostability in aqueous solutions, the complexation of ofloxacin with β-cyclodextrin was investigated. The complexes showed a water solubility enhancement of approximately 2.6 times; nevertheless, the photodegradation of ofloxacin was not reduced. The complexes obtained were characterized by thermal and ¹H nuclear magnetic resonance (NMR) analysis, which revealed an interaction between ofloxacin and β-cyclodextrin. The last analysis indicated that only partial inclusion of the N-methylpiperazinyl moiety occurred, which can explain the fact that photostabilization was not improved. This partial inclusion phenomenon could be explained also by computer-aided molecular modeling.     

Cyclodextrin polyurethanes polymerized with multi-walled carbon nanotubes: Synthesis and characterization

Insoluble cyclodextrin polymers co-polymerized with multi-walled carbon nanotubes were synthesized by polymerizing β-cyclodextrin with acid-functionalized multi-walled carbon nanotubes and diisocyanate linkers; hexamethylene- and toluene-2,4-diisocyanate. The polymers are useful in removing some organic pollutants from water, and we now report the full characterization of these polymers using infrared spectroscopy (IR), Raman spectroscopy, scanning and transmission electron microscopy (SEM and TEM) and thermal techniques such as thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC).The polymers could be synthesized as either powders or amorphous solids. Results of the IR analysis showed the presence of functional groups such as CO, CC, CH and CO, indicating that polymerization indeed took place. Characterization of the polymers by scanning electron microscopy and BET analysis showed that these polymers had a spongy appearance indicating a hierarchical pore structure. Incorporation of small amounts (<5%) of multi-walled nanotubes (MWNTs) improved the thermal stability of the polymers. This observation was further confirmed by differential scanning calorimetry (DSC) measurements.     

Solubilization of the neutral and charged forms of 2,4,6-trichlorophenol by beta-cyclodextrin,methyl-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin in water

The solubilities of the neutral and charged forms of 2,4,6-trichlorophenol (TCP) in β-cyclodextrin (β-CD) and two of its most used derivatives: methyl-β-cyclodextrin (MCD) and hydroxypropyl-β-cyclodextrin (HPCD) solutions were investigated. The three cyclodextrins were found to form 1:1 inclusion complexes. Binding constants estimated from an enhancement solubility method revealed that the stability of the complexes was dependent on the polarity of the compound and on the cyclodextrin used.

In general, weaker binding constants were observed for TCP with β-CD than with HPCD or MCD. The solubilization efficiencies towards TCP can be ranked in the following order: MCD > HPCD > β-CD. For all cyclodextrins, the stability constant of neutral TCP (log K_ow=3.85) was larger than that of charged TCP (log K_ow=1.4).

A precipitation occurred in TCP/β-CD solution (around 10 g/l β-CD concentration) at pH 3. However, this phenomenon is not observed for TCP/β-CD solution at pH 8.8.     

Effect of hydroxypropyl-beta-cyclodextrin on the solubility of an antibacterial isoxazolyl-naphthoquinone

The complexation of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (I) with a highly soluble cyclodextrin, hydroxypropyl-β-cyclodextrin (HP-β-CD) was studied in aqueous media by solubility methods. I is an antibacterial and trypanocidal agent that is undergoing preclinical testing. Unfortunately, I exhibits low water solubility, and it is therefore difficult to prepare the solutions for biological tests. I inclusion took place with 1:1 stoichiometry. The stability constants of the I complexes calculated from the slope and the intercept of the phase solubility diagrams are larger in the less ionized form, whereas greater overall solubility is obtained in basic media.     

Celecoxib-cyclodextrin systems: characterization and evaluation of in vitro and in vivo advantage

Solid dispersions of Celecoxib were prepared with hydroxypropyl β cyclodextrin by various methods such as physical mixture, cogrinding, kneading, and coevaporation. The dispersions were characterized by differential scanning calorimetry (DSC), X-ray diffraction patterns, infrared spectroscopy, and nuclear magnetic resonance studies. The DSC thermograms of the dispersions indicated potential of heat-induced interaction between Celecoxib and cyclodextrin that could influence in vitro drug dissolution. The dispersions exhibited faster rates of dissolution compared to that of Celecoxib. The kneaded dispersion with the fastest in vitro dissolution rate when compressed into tablets showed a better release profile compared to the tablets of pure Celecoxib. In vivo studies revealed that the kneaded dispersion provided for quicker response and was more effective in inhibiting rat paw edema as compared to Celecoxib alone, thus confirming the advantage of improved pharmacological activity of Celecoxib when administered as a solid dispersion with cyclodextrin.     

The effect of 2-hydroxypropyl-beta-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.     

Drug-beta-cyclodextrin containing pellets prepared with a high-shear mixer

This work was aimed at investigating the preparation of β-cyclodextrin-microcrystalline cellulose pellets by means of a high-shear mixer, both in the absence or in the presence of ibuprofen as model drug. Drug loading of pellets was accomplished by means of two alternative techniques: 1) solution layering or 2) powder layering. The prepared pellets were characterised in terms of size distribution, shape factor, friability and dissolution rate. The interaction between ibuprofen and β-cyclodextrin was monitored by Differential Scanning Calorimetry (DSC). Micro Fourier Transform Infrared spectroscopy (MicroFTIR) was applied to determine the distribution of components within each pellet on a micro scale. Pellets with narrow size distribution and containing up to about 90% of BCD were prepared using water as binder. The process yield resulted around 84 and 63% for drug-free and medicate pellets respectively. Drug loaded pellets with favourable technological and biopharmaceutical characteristics can be obtained both by powder or solution layering techniques. The latter proved to be more suitable for producing pellets with high drug contents, reduced friability and high drug dissolution rates.     

Investigation of CdTex and Cd1-xZnxTe Schottky Barrier Diode Structure Based γ-Ray Detectors

Cadmium Telluride (CdTe) and Cadmium Zinc Telluride (CdZnTe) based detectors have been developed for hard X-ray and γ -ray detection. These semiconducting materials have high resistivity because of the wide bandgap and also have high photon absorption efficiency because of the large atomic number (Z_Cd = 48, Z_Te = 52). CdTe and CdZnTe substrates (7 mm × 9 mm × 0.5 mm) with different stoichiometry were taken for the fabrication of γ-ray detectors. The substrate was prepared by polishing the bulk crystals grown by the rotational Bridgman method. Crystals with maximum electrical resistivity were grown in this way. For fabrication of Schottky barrier diode structures, the Schottky contacts were made by electroless deposition for gold (Au) and thermal evaporation for Indium (In). The Au/CdTe/In and Au/CdZnTe/In Schottky barrier diodes were linked to the charge sensitive preamplifier by gold wires. Then, I-V measurement and detector efficiency like charge collection performance with energy resolutions were analyzed at room temperature by using ⁵⁷Co and ¹³⁷Cs gamma sources. The good energy resolutions of ⁵⁷Co (122 KeV) and ¹³⁷Cs (662 KeV) sources are obtained for both CdTe and CdZnTe diode detectors.     

Quantitative analysis of beta-blockers in pharmaceutical preparations by capillary electrophoresis

A simple capillary electrophoresis method was developed for the analysis of four β-blockers (atenolol, metoprolol, pindolol, and propranolol) in pharmaceutical preparations. The method was validated regarding accuracy, precision, linearity, and detection/quantification limits, and the obtained values were in accordance to those reported in the literature. The method was applied to the determination of the drugs in commercial tablet preparations and proved to be fast and reliable for the quantitative analysis of the β-blockers.     

Extrusion granulation and high shear granulation of different grades of lactose and highly dosed drugs: a comparative study

Formulations containing different lactose grades, paracetamol, and cimetidine were granulated by extrusion granulation and high shear granulation. Granules were evaluated for yield, friability, and compressibility. Tablets were prepared from those granules and evaluated for tensile strength, friability, disintegration time, and dissolution. The different lactose grades had an important effect on the extrusion granulation process. Particle size and morphology affected powder feeding and power consumption, but had only a minor influence on the granule and tablet properties obtained by extrusion granulation. In contrast, the lactose grades had a major influence on the granule properties obtained by high shear granulation. Addition of polyvinylpyrrolidone (PVP) was required to process pure paracetamol and cimetidine by high shear granulation, whereas it was feasible to granulate these drugs without PVP by extrusion granulation. Granules prepared by extrusion granulation exhibited a higher yield and a lower friability than those produced by high shear granulation. Paracetamol and cimetidine tablets compressed from granules prepared by extrusion granulation showed a higher tensile strength, lower friability, and lower disintegration time than those prepared from granules produced by high shear granulation. Paracetamol tablets obtained via extrusion granulation exhibited faster dissolution than those obtained via high shear granulation. For all lactose grades studied, extrusion granulation resulted in superior granule and tablet properties in comparison with those obtained by high shear granulation. These results indicate that extrusion granulation is more efficient than high shear granulation.     

Bimodal Size Distribution and Shape Anisotropy in Ball-Milled Nano-Sized α-Al2O3

-Al₂O₃ prepared by combustion technique was ball-billed in a planetary mill in toluene medium at 300 rpm in ZrO₂ pot with a ball to powder ratio 10:1 for 1, 5, 10, 15, and 20 hours. X-ray diffraction pattern from the milled materials showed super-Lorentzian peak shapes for -Al₂O₃ peak profiles. The super-Lorentzian peak shape has been attributed to the bimodal size distribution of the -Al₂O₃ particles. Rietveld analysis using two different phase fractions of -Al₂O₃ with different microstructural features yielded a low goodness-of-fit of the x-ray data indicating the suitability of the assumed model. The phase fraction of -Al₂O₃ particles with smaller size increases with the milling time. Further the particles shapes were observed to be cylindrical in this case with the cylinder axis along the crystallographic c-axis. The cylinder diameter and the length were obtained to be 86  and 140  respectively after 20 hrs of milling. The -Al₂O₃ particles of larger size are isotropic. It is, thus, proposed that milling induces bimodal size distribution in the initial hours of milling.     

Mechanical spectroscopy of thin layers of PPV polymer on Si substrates

The vibrating reed technique with electro“static” excitation and optical detection has been applied to investigate thin layers of poly-phenylene-vinylene, deposited by spin coating onto microfabricated Si cantilevers, during temperature cycling programs between 90 and 540 K at a rate of 1 K/min. From the vibration frequencies the Young’s modulus of the film can be estimated to be about 10 MPa at room temperature in the precursor phase (if prepared from a solution in toluene), which increases by conversion to the conjugate bonded polymer to about 50 MPa. The temperature dependence of internal friction reveals the processes of γ relaxations (crankshaft motion of side branches in the precursor) and β-relaxation (movements of a few monomer blocks in the polymer chain), as well as peaks indicating the structural transformations during conversion, and possibly a glass transition in the amorphous precursor phase. After conversion only the β-relaxation persists.     

络合法制备均匀γ-Fe2O3纳米颗粒@多层石墨烯复合材料研究

采用水热反应中的金属离子络合一步制备均匀超细磁性γ-Fe₂O₃纳米颗粒@多层石墨烯复合材料, 无需对石墨烯进行氧化处理。采用超声法制备多层石墨烯作为基片, 制备方法简单, 石墨烯表面的含氧官能团少。以FeCl₂为反应物, 以DMF(N, N二甲基甲酰胺)和水混合液作为溶剂, 其中DMF能起到络合金属离子的作用。实验研究了乙酸钠、反应温度及填充度对制备产物的影响。采用X射线衍射(XRD)、X射线光电子能谱(XPS)、扫描电子显微镜(SEM)、透射电子显微镜(TEM)对复合材料进行微结构分析, 采用振动样品磁强计(VSM)测试了复合材料的磁性能。研究结果表明: 利用亚铁离子与DMF形成的络合物与碳环的π-π吸附作用可以在多层石墨烯表面生成铁氧化物。通过控制亚铁离子的氧化速度和氧化铁的生长速度, 在多层石墨烯表面获得了尺寸小于10 nm的均匀γ-Fe₂O₃纳米颗粒, 复合材料具有良好的磁性能。     

γ-NaxCoO2粉体的聚丙烯酸钠凝胶法制备及其表征

本研究发展了一种用于制备氧化物热电材料γ-Na_xCoO₂粉体的化学合成方法——聚丙烯酸钠(PAAS)凝胶法。主要研究了PAAS/Co²⁺摩尔比、原料浓度和煅烧温度对产物相组成及微观形态的影响规律, 探讨了物相形成机制, 同时用该方法结合SPS制备了不同Na离子浓度的Na_xCoO₂多晶样品, 并对其热电性能进行了表征。结果表明, PAAS/Co²⁺摩尔比对产物相组成产生了显著影响, 随着PAAS/Co²⁺摩尔比的增加, 样品的相组成由Co₃O₄相向单相γ-Na_xCoO₂转变, 合适的PAAS/Co²⁺摩尔比为0.8~1.1。而反应原料浓度对产物相组成的影响存在一个临界值(0.025 mol/L), 大于临界值抑制单相形成, 小于临界值促进单相形成。煅烧温度的升高有助于γ-Na_xCoO₂单相的形成, 800℃煅烧得到γ-Na_xCoO₂单相, 晶粒形态呈片状, 平均厚度约200 nm, 片状方向的尺寸在1~4 μm之间。随着Na含量的增加, 样品的Seebeck系数增大, 电导率增加, 热导率降低, 最终导致ZT值大幅增加。     

The physicochemical characterization and in vitro/in vivo evaluation of natural surfactants-based emulsions as vehicles for diclofenac diethylamine

Two sugar-based emulsifiers, cetearyl alcohol & cetearyl glycoside and sorbitan stearate & sucrose cocoate, known as potential promoters of lamellar liquid crystals/gel phases, were investigated in order to formulate an optimal vehicle for amphiphilic drug—diclofenac diethylamine (DDA).

Physico-chemical characterization and study of vehicle's physical stability were performed. Then, the in vitro DDA liberation profile, dependent on the mode of drug incorporation to the system, and the in vivo, short-term effects of chosen samples on skin parameters were examined.

Droplets size distribution and rheological behavior indicated satisfying physical stability of both types of vehicles. Unexpectedly, the manner of DDA incorporation to the system had no significant influence on DDA release. In vivo study pointed to emulsion's favorable potential for skin hydration and barrier improvement, particularly in cetearyl glycoside-based vehicle.