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.

The effects of season and dietary salt content on body temperature daily rhythms of common spiny mice from different micro-habitats

We compared body temperature (T-b) daily rhythms in two populations of common spiny mice, Acomys cahirinus, during summer and winter months in relation to increasing dietary salt content. Mice were collected from the North and South facing slopes (NFS and SFS) of the same valley, that are exhibiting mesic and xeric habitats, respectively. During the summer, whilst mice were offered a water source containing 0.9% NaCl, SFS individuals had T-b peak values at 24:00, whereas NFS individuals had peak values at 18:00. When the salinity of the water source was increased, from 0.9 to 2.5% and then 3.5%, the difference between maximal and minimal T-b of both populations increased. In addition, with increased salinity, the T-b daily peak of SFS mice shifted to 18:00. During the winter, the mean daily T-b values of both populations of mice were lower than during the summer. At 0.9% salinity, the NFS mice exhibited a daily T-b variation with a peak at the beginning of the night. However, we did not detect any significant variation in daily T-b in the SFS mice. At 2.5% salinity, the difference between the mean daily T-b of mice from the two slopes increased. In winter we were unable to increase the salinity to 3.5% as the animals began to lose weight rapidly. We suggest that common spiny mice that inhabit these two micro-habitats axe forming two discrete populations that respond differently to the environmental pressures prevailing in each habitat, by evolving different physiological capacities. (C) 2002 Elsevier Science Inc. All rights reserved.

Experimentally elevated plasma testosterone levels do not influence singing behaviour of male blue tits (Parus caeruleus) during the early breeding season

Sexual selection theory suggests that females might prefer males on the basis of testosterone (T)-dependent secondary sexual traits such as song. Correlational studies have linked high plasma T-levels to high diurnal song output. This has been confirmed in experiments where T-levels were kept high at times when natural T-levels have decreased. However, surprisingly little is known about the relation between T-levels during the early breeding season and song. In many passerine birds males sing at a high rate at dawn early in the breeding season, referred to as the dawn chorus. In blue tits (Parus caeruleus), the dawn chorus coincides with the fertile period of the female, whereas diurnal song occurs throughout the breeding season. Previous studies on blue tits showed that characteristics of the dawn chorus correlate with male reproductive success. We experimentally elevated plasma T-levels in male blue tits during the pre-fertile and fertile period. Our aim was to test whether increased plasma T-levels affect dawn song characteristics and increase the amount of diurnal song. Although T-implants successfully raised circulating T-levels, we did not find any difference between T- and control males in temporal performance measures of dawn song or in diurnal song output. Our results suggest that either there is no direct causal link between song output or quality and individual T-levels, or experimental manipulations of T-levels using implants do not permit detection of such effects during the early breeding season. Although we cannot exclude that individual T-levels are causally linked to other (e.g. structural) song parameters, our results cast doubt on T-dependence as the mechanisms that enforces honesty on song as a sexually selected trait.

The natural plasma testosterone profile of male blue tits during the breeding season and its relation to song output

In male birds, the gonadal hormone testosterone (T) is known to influence territorial and mating behaviour. Plasma levels of T show seasonal fluctuations which vary in relation to mating system and social instability. First, we determined the natural T profile of male blue tits Parus caeruleus during the breeding season. We found that plasma levels of T increased at the onset of nest building. Thus, the increase in circulating T was not associated with territory establishment, nor with the fertile period of the males' mates. In most individuals, T levels dropped to values close to zero during the period of chick feeding. Second, we investigated the relationship between plasma levels of T and male age, size, and singing behaviour. During the mating period, T levels did not differ between 1 yr old and older males and did not correlate with body size or condition. However, song output during the dawn chorus tended to be positively correlated with T levels. Therefore, if high T levels are costly, song output might be an honest indicator of male quality in blue tits. Finally, we show that plasma levels of T are significantly higher during the night than during the day. This pattern has also been observed in captive non-passerine birds, but its functional significance remains unknown.

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.

Nucleation and growth in fluidised hot melt granulation

Fluidised hot melt granulation (FHMG) is a novel technology for granulation process in pharmaceutical industry, which has distinct advantages over other commercial techniques. The aim of this research was to investigate granulation and the effect of process parameters that may affect FHMG process. In this work, ballotini beads were used as the model particles and Lutrol (R) F 68 Poloxamer 188 was used as meltable solid binder. In order to determine the granulation and nucleation mechanism in this co-melt FHMG system, several parameters were investigated, such as binder content, particle size of binder and particle size and hydrophobicity of ballotini. These parameters were correlated to granule size distribution, mean granule size and granule shape. Furthermore, these experimental investigations were designed so that the coalescence model could be applied to the co-melt FHMG system. The analysis indicated that the non-inertial regime extends over a relatively short time period of