Development of novel oral formulations prepared via hot melt extrusion for targeted delivery of photosensitizer to the colon

Colon-residing bacteria, such as vancomycin-resistant Enterococcus faecalis and Bacteroides fragilis, can cause a range of serious clinical infections. Photodynamic antimicrobial chemotherapy (PACT) may be a novel treatment option for these multidrug resistant organisms. The aim of this study was to formulate a Eudragit®-based drug delivery system, via hot melt extrusion (HME), for targeting colonic release of photosensitizer. The susceptibility of E. faecalis and B. fragilis to PACT mediated by methylene blue (MB), meso-tetra(N-methyl-4-pyridyl)porphine tetra-tosylate (TMP), or 5-aminolevulinic acid hexyl-ester (h-ALA) was determined, with tetrachlorodecaoxide (TCDO), an oxygen-releasing compound, added in some studies. Results show that, for MB, an average of 30% of the total drug load was released over a 6-h period. For TMP and h-ALA, these values were 50% and 16% respectively. No drug was released in the acidic media. Levels of E. faecalis and B. fragilis were reduced by up to 4.67 and 7.73 logs, respectively, on PACT exposure under anaerobic conditions, with increased kill associated with TCDO. With these formulations, photosensitizer release could potentially be targeted to the colon, and colon-residing pathogens killed by PACT. TCDO could be used in vivo to generate oxygen, which could significantly impact on the success of PACT in the clinic.

Modeling of Turbulent Natural Gas and Biogas Flames of the Delft Jet-in-Hot-Coflow Burner: Effects of Coflow Temperature, Fuel Temperature and Fuel Composition on the Flame Lift-Off Height

The structure of a turbulent non-premixed flame of a biogas fuel in a hot and diluted coflow mimicking moderate and intense low dilution (MILD) combustion is studied numerically. Biogas fuel is obtained by dilution of Dutch natural gas (DNG) with CO2. The results of biogas combustion are compared with those of DNG combustion in the Delft Jet-in-Hot-Coflow (DJHC) burner. New experimental measurements of lift-off height and of velocity and temperature statistics have been made to provide a database for evaluating the capability of numerical methods in predicting the flame structure. Compared to the lift-off height of the DNG flame, addition of 30 % carbon dioxide to the fuel increases the lift-off height by less than 15 %. Numerical simulations are conducted by solving the RANS equations using Reynolds stress model (RSM) as turbulence model in combination with EDC (Eddy Dissipation Concept) and transported probability density function (PDF) as turbulence-chemistry interaction models. The DRM19 reduced mechanism is used as chemical kinetics with the EDC model. A tabulated chemistry model based on the Flamelet Generated Manifold (FGM) is adopted in the PDF method. The table describes a non-adiabatic three stream mixing problem between fuel, coflow and ambient air based on igniting counterflow diffusion flamelets. The results show that the EDC/DRM19 and PDF/FGM models predict the experimentally observed decreasing trend of lift-off height with increase of the coflow temperature. Although more detailed chemistry is used with EDC, the temperature fluctuations at the coflow inlet (approximately 100K) cannot be included resulting in a significant overprediction of the flame temperature. Only the PDF modeling results with temperature fluctuations predict the correct mean temperature profiles of the biogas case and compare well with the experimental temperature distributions.

The Physical and Chemical Structure of Hot Molecular Cores

We have made self-consistent models of the density and temperature profiles of the gas and dust surrounding embedded luminous objects using a detailed radiative transfer model together with observations of the spectral energy distribution of hot molecular cores. Using these profiles we have investigated the hot core chemistry which results when grain mantles are evaporated, taking into account the different binding energies of the mantle molecules, as well a model in which we assume that all molecules are embedded in water ice and have a common binding energy. We find that most of the resulting column densities are consistent with those observed toward the hot core G34.3+0.15 at a time around 10^4 years after central luminous star formation. We have also investigated the dependence of the chemical structure on the density profile which suggests an observational possibility of constraining density profiles from determination of the source sizes of line emission from desorbed molecules.

The manufacture and characterisation of hot-melt extruded enteric tablets

The aim of this highly novel study was to use hot-melt extrusion technology as an alternative process to enteric coating. In so doing, oral dosage forms displaying enteric properties may be produced in a continuous, rapid process, providing significant advantages over traditional pharmaceutical coating technology. Eudragit (R) L100-55, an enteric polymer, was pre-plasticized with triethyl citrate (TEC) and citric acid and subsequently dry-mixed with 5-aminosalicylic acid, a model active pharmaceutical ingredient (API), and an optional gelling agent (PVP (R) K30 or Carbopol (R) 971P). Powder blends were hot-melt extruded as cylinders, cut into tablets and characterised using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dissolution testing conducted in both pH 1.2 and pH 6.8 buffers. Increasing the concentration of TEC significantly lowered the glass transition temperature (T,) of Eudragit (R) L100-55 and reduced temperatures necessary for extrusion as well as the die pressure. Moreover, citric acid (17% w/w) was shown to act as a solid-state plasticizer. HME tablets showed excellent gastro-resistance, whereas milled extrudates compressed into tablets released more than 10% w/w of the API in acidic media. Drug release from HME tablets was dependent upon the concentration of TEC, the presence of citric acid, PVP K30, and Carbopol (R) 971P in the matrix, and pH of the dissolution media. The inclusion of an optional gelling agent significantly reduced the erosion of the matrix and drug release rate at pH 6.8; however, the enteric properties of the matrix were lost due to the formation of channels within the tablet. Consequently this work is both timely and highly innovative and identifies for the first time a method of producing an enteric matrix tablet using a continuous hot-melt extrusion process.

WASP-4b: A 12th magnitude transiting hot Jupiter in the southern hemisphere

We report the discovery of WASP-4b, a large transiting gas-giant planet with an orbital period of 1.34 days. This is the first planet to be discovered by the SuperWASP-South observatory and CORALIE collaboration and the first planet orbiting a star brighter than 16th magnitude to be discovered in the southern hemisphere. A simultaneous fit to high-quality light curves and precision radial velocity measurements leads to a planetary mass of 1.22(-0.08)(+0.09) M-Jup and a planetary radius of 1.42(-0.04)(+0.07) R-Jup. The host star is USNO-B1.0 0479-0948995, a G7 V star of visual magnitude 12.5. As a result of the short orbital period, the predicted surface temperature of the planet is 1761 K, making it an ideal candidate for detections of the secondary eclipse at infrared wavelengths.

Body temperature daily rhythm adaptations in African savanna elephants (Loxodonta africana)

The savanna elephant is the largest extant mammal and often inhabits hot and and environments. Due to their large size, it might be expected that elephants have particular physiological adaptations, such as adjustments to the rhythms of their core body temperature (T-b) to deal with environmental challenges. This study describes for the first time the T-b daily rhythms in savanna elephants. Our results showed that elephants had lower mean T-b values (36.2 +/- 0.49 degrees C) than smaller ungulates inhabiting similar environments but did not have larger or smaller amplitudes of T-b variation (0.40 +/- 0.12 degrees C), as would be predicted by their exposure to large fluctuations in ambient temperature or their large size. No difference was found between the daily T-b rhythms measured under different conditions of water stress. Peak T-b's occurred late in the evening (22: 10) which is generally later than in other large mammals ranging in similar environmental conditions. (C) 2007 Elsevier Inc. All rights reserved.

The effect of H-2 and the presence of hot-O-(ads) during the decomposition of N2O on platinum

The decomposition of N2O was studied using a silica-supported Pt catalyst. The catalyst was found to exhibit short-lived activity at low temperatures to yield N-2 and O-(ads), the latter remained adsorbed on the surface and poisoned the active sites. Creation of hot-O-(ads) atoms during N2O decomposition is proposed to allow O-2 desorption at intermediate temperatures. Inclusion of H-2 as a reducing agent greatly enhanced the activity and suppressed low temperature deactivation. Simultaneous and sequential pulsing of N2O and H-2 showed that H-2 inclusion with the N2O gas stream produced the greatest activity. A mechanism involving H-(ads) addition to

Cyanopolyynes in hot cores: modelling G305.2+0.2

We present results from a time-dependent gas-phase chemical model of a hot core based on the physical conditions of G305.2+0.2. While the cyanopolyyne HC3N has been observed in hot cores, the longer chained species, HC5N, HC7N and HC9N, have not been considered as the typical hot-core species. We present results which show that these species can be formed under hot core conditions. We discuss the important chemical reactions in this process and, in particular, show that their abundances are linked to the parent species acetylene which is evaporated from icy grain mantles. The cyanopolyynes show promise as ‘chemical clocks’ which may aid future observations in determining the age of hot core sources. The abundance of the larger cyanopolyynes increases and decreases over relatively short time-scales, ~10^2.5 yr. We present results from a non-local thermodynamic equilibrium statistical equilibrium excitation model as a series of density, temperature and column density dependent contour plots which show both the line intensities and several line ratios. These aid in the interpretation of spectral-line data, even when there is limited line information available. In particular, non-detections of HC5N and HC7N in Walsh et al. are analysed and discussed.

WASP-24 b: A New Transiting Close-in Hot Jupiter Orbiting a Late F-star

We report the discovery of a new transiting close-in giant planet, WASP-24 b, in a 2.341 day orbit, 0.037 AU from its F8-9 type host star. By matching the star's spectrum with theoretical models, we infer an effective temperature T eff = 6075 ± 100 K and a surface gravity of log g = 4.15 ± 0.10. A comparison of these parameters with theoretical isochrones and evolutionary mass tracks places only weak constraints on the age of the host star, which we estimate to be 3.8+1.3 –1.2 Gyr. The planetary nature of the companion was confirmed by radial velocity measurements and additional photometric observations. These data were fit simultaneously in order to determine the most probable parameter set for the system, from which we infer a planetary mass of 1.071+0.036 –0.038 M Jup and radius 1.3+0.039 –0.037 R Jup.

Nonlinear modulation of ion-acoustic waves in two-electron-temperature plasmas

The amplitude modulation of ion-acoustic waves IS investigated in a plasma consisting of adiabatic warm ions, and two different populations of thermal electrons at different temperatures. The fluid equations are reduced to nonlinear Schrodinger equation by employing a multi-scale perturbation technique. A linear stability analysis for the wave packet amplitude reveals that long wavelengths are always stable, while modulational instability sets in for shorter wavelengths. It is shown that increasing the value of the hot-to-cold electron temperature ratio (mu), for a given value of the hot-to-cold electron density ratio (nu): favors instability. The role of the ion temperature is also discussed. In the limiting case nu = 0 (or nu -> infinity). which correspond(s) to an ordinary (single) electron-ion plasma, the results of previous works are recovered.