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.

Influence of process parameters on fluidised hot-melt granulation and tablet pressing of pharmaceutical powders

This study investigates the influence of process parameters on the fluidised hot melt granulation of lactose and PEG 6000, and the subsequent tablet pressing of the granules. Granulation experiments were performed to assess the effect of granulation time and binder content of the feed on the resulting granule properties such as mass mean granule size, size distribution, granule fracture stress, and granule porosity. These data were correlated using the granule growth regime model. It was found that the dominant granule growth mechanisms in this melt granulation system were nucleation followed by steady growth (PEG 10–20% w/w). However, with binder contents greater than 20% w/w, the granulation mechanism moved to the “over-wet massing” regime in which discrete granule formation could not be obtained. The granules produced in the melt fluidised bed process were subsequently pressed into tablets using an industrial tablet press. The physical properties of the tablets: fracture stress, disintegration time and friability were assessed using industry standards. These analyses indicated that particle size and binder content of the initial granules influenced the mechanical properties of the tablets. It was noted that a decrease in initial granule size resulted in an increase in the fracture stress of the tablets formed.

A detailed abundance analysis of the hot post-AGB star ZNG-1 in M10

We present a model-atmosphere analysis for the bright (V similar to 13) star ZNG-1, in the globular cluster M10. From high-resolution (R similar to 40 000) optical spectra we confirm ZNG-1 to be a post-asymptotic giant branch (post-AGB) star. The derived atmospheric parameters are T-eff = 26 500 +/- 1000 K and log g = 3.6 +/- 0.2 dex. A differential abundance analysis reveals a chemical composition typical of hot post-AGB objects, with ZNG-1 being generally metal poor, although helium is approximately solar. The most interesting feature is the large carbon underabundance of more than 1.3 dex. This carbon deficiency, along with an observed nitrogen enhancement relative to other elements, may suggest that ZNG-1 evolved off the AGB before the third dredge-up occurred. Also, iron depletions observed in other similar stars suggest that gas- dust fractionation in the AGB progenitor could be responsible for the observed composition of these objects. However, we need not invoke either scenario since the chemical composition of ZNG-1 is in good agreement with abundances found for a Population II star of the same metallicity.

A chemical analysis of five hot stars towards the Galactic centre

High resolution echelle spectroscopy is presented for thirteen stars lying in the direction of the Galactic centre which, on the basis of photographic photometry and low dispersion spectroscopy, have been classified as early-B-type. Eight of these stars have large rotational velocities which preclude a detailed analysis. The five stars with moderate to low projected rotational velocities have been analysed using model atmosphere techniques to determine atmospheric parameters and chemical compositions. Two of these stars appear to be evolved blue horizontal branch objects on the basis of their chemical compositions and small projected rotational velocity. The evolutionary status of a third is ambiguous but it is probably a post-asymptotic-giant branch star. The remaining two objects are probably young massive stars and show enhanced abundances of N, C, Mg and Si, consistent with their formation in the inner part of the Galactic disk. However their O abundances are normal, confirming results found previously for other early- type stars, which would imply a flat abundance gradient for this element in the inner region of our Galaxy.

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.

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

Acoustic solitary waves in dusty and/or multi-ion plasmas with cold, adiabatic, and hot constituents

Large nonlinear acoustic waves are discussed in a four-component plasma, made up of two superhot isothermal species, and two species with lower thermal velocities, being, respectively, adiabatic and cold. First a model is considered in which the isothermal species are electrons and ions, while the cooler species are positive and/or negative dust. Using a Sagdeev pseudopotential formalism, large dust-acoustic structures have been studied in a systematic way, to delimit the compositional parameter space in which they can be found, without restrictions on the charges and masses of the dust species and their charge signs. Solitary waves can only occur for nonlinear structure velocities smaller than the adiabatic dust thermal velocity, leading to a novel dust-acoustic-like mode based on the interplay between the two dust species. If the cold and adiabatic dust are oppositely charged, only solitary waves exist, having the polarity of the cold dust, their parameter range being limited by infinite compression of the cold dust. However, when the charges of the cold and adiabatic species have the same sign, solitary structures are limited for increasing Mach numbers successively by infinite cold dust compression, by encountering the adiabatic dust sonic point, and by the occurrence of double layers. The latter have, for smaller Mach numbers, the same polarity as the charged dust, but switch at the high Mach number end to the opposite polarity. Typical Sagdeev pseudopotentials and solitary wave profiles have been presented. Finally, the analysis has nowhere used the assumption that the dust would be much more massive than the ions and hence, one or both dust species can easily be replaced by positive and/or negative ions and the conclusions will apply to that plasma model equally well. This would cover a number of different scenarios, such as, for example, very hot electrons and ions, together with a mix of adiabatic ions and dust (of either polarity) or a very hot electron-positron mix, together with a two-ion mix or together with adiabatic ions and cold dust (both of either charge sign), to name but some of the possible plasma compositions.

Spin-orbit angle measurements for six southern transiting planets. New insights into the dynamical origins of hot Jupiters

Context. Several competing scenarios for planetary-system formation and evolution seek to explain how hot Jupiters came to be so close to their parent stars. Most planetary parameters evolve with time, making it hard to distinguish between models. The obliquity of an orbit with respect to the stellar rotation axis is thought to be more stable than other parameters such as eccentricity. Most planets, to date, appear aligned with the stellar rotation axis; the few misaligned planets so far detected are massive (> 2 MJ). Aims: Our goal is to measure the degree of alignment between planetary orbits and stellar spin axes, to search for potential correlations with eccentricity or other planetary parameters and to measure long term radial velocity variability indicating the presence of other bodies in the system. Methods: For transiting planets, the Rossiter-McLaughlin effect allows the measurement of the sky-projected angle ß between the stellar rotation axis and a planet's orbital axis. Using the HARPS spectrograph, we observed the Rossiter-McLaughlin effect for six transiting hot Jupiters found by the WASP consortium. We combine these with long term radial velocity measurements obtained with CORALIE. We used a combined analysis of photometry and radial velocities, fitting model parameters with the Markov Chain Monte Carlo method. After obtaining ß we attempt to statistically determine the distribution of the real spin-orbit angle ?. Results: We found that three of our targets have ß above 90°: WASP-2b: ß = 153°+11-15, WASP-15b: ß = 139.6°+5.2-4.3 and WASP-17b: ß = 148.5°+5.1-4.2; the other three (WASP-4b, WASP-5b and WASP-18b) have angles compatible with 0°. We find no dependence between the misaligned angle and planet mass nor with any other planetary parameter. All six orbits are close to circular, with only one firm detection of eccentricity e = 0.00848+0.00085-0.00095 in WASP-18b. No long-term radial acceleration was detected for any of the targets. Combining all previous 20 measurements of ß and our six and transforming them into a distribution of ? we find that between about 45 and 85% of hot Jupiters have ? > 30°. Conclusions: Most hot Jupiters are misaligned, with a large variety of spin-orbit angles. We find observations and predictions using the Kozai mechanism match well. If these observational facts are confirmed in the future, we may then conclude that most hot Jupiters are formed from a dynamical and tidal origin without the necessity to use type I or II migration. At present, standard disc migration cannot explain the observations without invoking at least another additional process.

The effect of the binder size and viscosity on agglomerate growth in fluidised hot melt granulation

Fluidised hot melt granulation (FHMG) is a novel granulation technique for processing pharmaceutical powders. Several process and formulation parameters have been shown to significantly influence granulation characteristics within FHMG. In this study we have investigated the effect of the binder properties (binder particle size and binder viscosity) on agglomerate growth mechanisms within FHMG. Low-melting point co-polymers of polyoxyethylene–polyoxypropylene (Lutrol® F68 Poloxamer 188 and Lutrol® F127 Poloxamer 407) were used as meltable binders for FHMG, while standard ballotini beads were used as model fillers for this process. Standard sieve analysis was used to determine the size distribution of granules whereas we utilised fluorescence microscopy to investigate the distribution of binder within granules. This provided further insight into the growth mechanisms during FHMG. Binder particle size and viscosity were found to affect the onset time of granulation. Agglomerate growth achieved equilibrium within short time-scales and was shown to proceed by two competing processes, breakage of formed granules and re-agglomeration of fractured granules. Breakage was affected by the initial material properties (binder size and viscosity). When using binder with a small particle size (<250 µm), agglomerate growth via a distribution mechanism dominated. Increasing the binder particle size shifted the granulation mechanism such that agglomerates were formed predominantly via immersion. A critical ratio between binder diameter and filler has been calculated and this value may be useful for predicting or controlling granulation growth processes.

The chemistry of deuterium in hot molecular cores

This paper presents the results of a model of the chemistry of deuterium-bearing molecules in hot molecular cores. It is found that because hydrogen- and deuterium-bearing molecules are destroyed by the same reactions at about the same rates, the initial fractionation present in ice mantles persists for over 10(4) yr. This is the case for a wide range of physical conditions, so it is safe to infer the fractionation on grain surfaces from observations of deuterated molecules in hot cores. The implications of the observed abundances of deuterium-bearing species in Orion are then discussed.

Mass-loss rates for hot luminous stars:The influence of line branching

The effect of photon frequency redistribution by line branching on mass-loss rates for hot luminous stars is investigated. Monte Carlo simulations are carried out for a range of OB star models which show that previous mass-loss calculations which neglect non-resonance line scattering overestimate mass-loss rates for luminous O stars by ~20 per cent. For luminous B stars the effect is somewhat larger, typically ~50 per cent. A Wolf-Rayet star model is used to investigate line branching in the strong wind limit. In this case the effect of line branching is much greater, giving mass-loss rates that are smaller by a factor ~3 from computations which neglect branching.

Investigation of influence of process variables on mechanical strength, size and homogeneity of pharmaceutical granules produced by fluidised hot melt granulation

The overall aim of the project was to study the influence of process variables on the distribution of a model active pharmaceutical ingredient (API) during fluidised melt granulation of pharmaceutical granules with a view of optimising product characteristics. Granules were produced using common pharmaceutical excipients; lactose monohydrate using poly ethylene glycol (PEG1500) as a meltable binder. Methylene blue was used as a model API. Empirical models relating the process variables to the granules properties such as granule mean size, product homogeneity and granule strength were developed using the design of experiment approach. Fluidising air velocity and fluidising air temperature were shown to strongly influence the product properties. Optimisation studies showed that strong granules with homogeneous distribution of the active ingredient can be produced at high fluidising air velocity and at high fluidising air temperatures.

Thermodynamically stable amorphous drug dispersions in amorphous hydrophilic polymers engineered by hot melt extrusion.

In this study thermodynamically stable dispersions of amorphous quinine, a model BCS class 2 therapeutic agent, within an amorphous polymeric platform (HPC), termed a solid-in-solid dispersion, were produced using hot melt extrusion. Characterisation of the pre-extrudates and extrudates was performed using hyper-differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Raman spectroscopy. Water uptake by the raw materials was determined using dynamic vapour sorption (DVS) analysis. Furthermore, the presence or absence of crystalline drug following storage at 25 °C/60% relative humidity and 40 °C/75% relative humidity in a sealed glass jar, and at 40 °C/75% relative humidity in an open glass jar for 3 months was determined using PXRD. Amorphous quinine was generated in situ during extrusion from both quinine base (5%, 10%, 20% w/w drug loading) and from quinine hydrochloride (5%, 10% w/w drug loading) and remained thermodynamically stable as a solid-in-solid dispersion within the HPC extrudates. When processed with HPC, quinine hydrochloride (20% w/w) was converted to amorphous quinine hydrochloride. Whilst stable for up to 3 months when stored under sealed conditions, this amorphous form was unstable, resulting in recrystallisation of the hydrochloride salt following storage for 1 month at 40 °C/75% relative humidity in an open glass jar. The behaviour of the amorphous quinine hydrochloride (20% w/w) HPC extrudate was related, at least in part, to the lower stability and the hygroscopic properties of this amorphous form.