Nanocrystalline Suspensions Research Articles

Photodecarbonylation of 1,3-Dithiophenyl Propanone: Using Nanocrystals to Overcome the Filtering Effect of Highly Absorbing Trace Impurities

Irradiation of crystalline 2,4-dimethyl-2,4-di(thiophen-3-yl)pentan-3-one (1) resulted in photodecarbonylation and radical combination to give 2 with >99% selectivity. However, extended irradiation led to no more than ca. 8% conversion due to highly absorbing unidentified trace impurities that act as filters. We report here a simple procedure to improve the reaction efficiency by taking advantage of nanocrystalline suspensions prepared by the reprecipitation method, which leads to shorter reaction times and quantitative yields.

Cogrinding enhances the oral bioavailability of EMD 57033, a poorly water soluble drug, in dogs

The oral bioavailability of EMD 57033, a calcium sensitizing agent with poor solubility, was compared in dogs using four solid dosage form formulation approaches: a physical blend of the drug with excipients, micronization of the drug, preparation of coground mixtures and spray-drying of the drug from a nanocrystalline suspension. The formulations contained generally accepted excipients such as lactose, hydroxypropylmethyl cellulose and sodium lauryl sulphate in usual quantities. Drug micronization and cogrinding was realized by a jet-milling technique. Nanoparticles were created by media milling using a bead mill. All formulations were administered orally as dry powders in hard gelatine capsules. While micronization increased the absolute bioavailability of the solid drug significantly compared to crude material (from nondetectable to 20%), cogrinding with specific excipients was able to almost double this improvement (up to 39%). With an absolute bioavailability of 26%, spray-dried nanoparticular EMD 57033 failed to show the superior bioavailability that had been anticipated from in vitro data. The control solution prepared with cyclodextrin was shown to have an absolute bioavailability of 57% (vs. i.v. infusion). It was concluded that cogrinding can be a useful tool to improve the bioavailability of poorly soluble drugs from a solid dosage form format.

Preparation of TiO<sub>2</sub> Nanocrystalline Films by Electrophoretic Deposition and their Application in Dye-Sensitized Solar Cells

TiO2 nanocrystalline films were prepared by electrophoretic deposition (EPD) under a pulseperiodic electric field. The EPD behavior of TiO2 nanocrystalline suspension was investigated. The uniform 9.2-μm-thick TiO2 film was obtained by reasonably controlling the EPD condition. A dye-sensitized solar cell, with the EPD TiO2 film as the photoanode, obtained about 4.1% of photon-to-electron conversion efficiency (η). Its Jsc, Voc and fill factor (ff) are 11.6 mA/cm2, 0.65 V and 0.55, respectively. The effect of TiCl4 modification on the photovoltaic property of the solar cell was also discussed.

Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection.

Clofazimine nanosuspensions were produced by high pressure homogenization and the formulation was optimized for lyophilization. Characterization of the product by photon correlation spectroscopy, laser diffraction and Coulter counter analysis showed that the clofazimine nanosuspensions were suitable for iv injection with a particle size permitting passive targeting to the reticuloendothelial system. Following iv administration to mice of either the nanocrystalline or a control liposomal formulation at a dose of 20 mg clofazimine/kg bodyweight, drug concentrations in livers, spleens and lungs reached comparably high concentrations, well in excess of the MIC for most Mycobacterium avium strains. When C57BL/6 mice were experimentally infected with M. avium strain TMC 724, nanocrystalline clofazimine was as effective as liposomal clofazimine in reducing bacterial loads in the liver, spleen and lungs of infected mice. Nanocrystalline suspensions of poorly soluble drugs such as riminophenazines are easy to prepare and to lyophilize for extended storage and represent a promising new drug formulation for intravenous therapy of mycobacterial infections.

Physical stability of ethyl diatrizoate nanocrystalline suspension in steam sterilization.

To study the effects of formulation variables on the physical stability of a submicron crystal (nanocrystal) suspension under steam sterilization conditions. Suspensions of ethyl diatrizoate nanocrystals were prepared by wet milling in the presence of the surfactant poloxamine 908. Particle size distribution and zeta potential were measured by photon correlation spectroscopy. On heating, the mean particle size of the nanocrystal suspension remained essentially unchanged up to 110 degrees C, the cloud point of the stabilizing surfactant, but increased significantly above that temperature. The increase in particle size was a result of particle aggregation rather than crystal growth. Adding a cloud point booster to the suspension significantly minimized the particle aggregation at high temperatures. The purity of poloxamine 908 and the tonicity agent and buffer salt used also affected the heat stability of the suspension, the latter agents apparently through altering the surfactant cloud point. The aggregation of the ethyl diatrizoate nanocrystalline suspension under steam sterilization conditions was a result of phase separation of the stabilizing surfactant at its cloud point. When formulated with a cloud point booster to prevent the phase-separation, the suspension maintained its physical stability under steam sterilization without any significant change in particle size distribution.

HPLC determination of clofazimine in tissues and serum of mice after intravenous administration of nanocrystalline or liposomal formulations

A simple HPLC method is described for the determination of clofazimine in mouse tissues and in serum. The main application of the method was the determination of the drug in mouse tissues after i.v. administration of nanocrystalline suspensions or liposomal encapsulated clofazimine. Tissues were extracted with a 10-fold (w/v) volume of an extraction solution consisting of methanol/glacial acetic acid 9:1 (v/v). Serum proteins were precipitated with a 2-fold volume of acetonitrile. Isocratic chromatography was performed using an anion exchange column (Nucleosil 100-5 SA, Macherey & Nagel) for separation. The mobile phase was a mixture of acetonitrile and 0.1 mol/l aqueous phosphoric acid (75:25, v/v), adjusted to pH 2.9 with sodium hydroxide solution. Absorption of the eluate was monitored at 495 nm. The assay was precise, simple to perform and fast. Recovery from tissues was ≥98%, from nanoparticles ≥98%, and from liposomes ≥96%. No interference was observed in extracts from mouse liver, spleen, lungs and human serum.

Nano-crystalline powders and suspensions generated using a flow-through hydrothermal process, Part II: Applications

Nano-crystalline powders and suspensions generated using a flow-through hydrothermal process, Part II: Applications

Nano-Crystalline Powders and Suspensions Generated Using A Flow-Through Hydrothermal Process, Part I: Characterization

ABSTRACTA wide range of ultra-fine, nano-crystalline powders and suspensions have been produced using the Rapid Thermal Decomposition of precursors in Solution (RTDS) technology. These materials include single and multi-component iron-, zirconium-, titanium-, nickel-, and chromium-oxide/oxyhydroxide powders. RTDS, which was developed at Pacific Northwest Laboratory, is a flow-through hydrothermal process capable of producing nano-crystalline particulate material at rates of up to 100 grams of solid per hour. We present the results of characterization efforts on RTDS iron oxyhydroxide and zirconium oxide systems. As-collected RTDS suspensions were characterized using optical light scattering. Separated RTDS powders were evaluated using X-ray diffraction, electron microscopy, gas adsorption analysis, thermal gravimetric analysis, and chemical analysis.

Nano-Crystalline Powders and Suspensions Generated Using A Flow-Through Hydrothermal Process, Part II: Applications

ABSTRACTUltra-fine, nano-crystalline six-line ferrihydrite (5Fe2O3-9H2O) and cubic zirconia (ZrÜ2) powders have been produced using the Rapid Thermal Decomposition of precursors in Solution (RTDS) technology. Nano-crystalline RTDS six-line ferrihydrite powder used as an in situ precursor for first-stage direct coal liquefaction catalysts increased the liquefied products from Blind Canyon Seam coal by 22% absolute over thermal background at 350°C. Initial sintering studies performed on nano-crystalline RTDS ZrO2 powder have also been presented and compared to predictions made from theories derived for micro-crystalline powders.