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.

Co-melt fluidised bed granulation of pharmaceutical powders: Improvements in drug bioavailability

This study investigates the use of co-melt fluidised bed granulation for the agglomeration of model pharmaceutical powders, namely, lactose mono-hydrate, PEG 10000, poly-vinyl pyrolidone and ibuprofen as a model drug. Granulation within the co-melt system was found to follow a nucleationâ??steady growthâ??coating regime profile. Using high molecular weight PEG binder, the granulation mechanism and thus the extent of granulation was found to be significantly influenced by binder viscosity. The compression properties of the granulate within the hot fluidised bed were correlated using a novel high temperature experimental procedure. It was found that the fracture stress and fractural modulus of the materials under hot processing conditions were orders of magnitude lower than those measured under ambient conditions. A range of particle velocities within the granulator were considered based on theoretical models. After an initial period of nucleation, the Stokes deformation number analysis indicated that only velocities within the high shear region of the fluidised bed were sufficient to promote significant granule deformation and therefore, coalescence. The data also indicated that larger granules de-fluidised preventing agglomeration by coalescence. Furthermore, experimental data indicated that dissipation of the viscous molten binder to the surface was the most important factor in the latter stages of the granulation process. From a pharmaceutical perspective the inclusion of the model drug, ibuprofen, combined with PVP in the co-melt process proved to be highly significant. It was found that using DSC analysis on the formulations that the decrease in the heat of fusion associated with the melting of ibuprofen within the FHMG systems may be attributed to interaction between PVP and ibuprofen through inter-molecular hydrogen bonding. This interaction decreases the crystallinity of ibuprofen and facilitates solubilisation and bioavailability within the solid matrix.

On the nature of the circumstellar medium of the remarkable Type Ia/IIn supernova SN 2002ic

We present results from the first high-resolution, high signal-to-noise ratio spectrum of SN 2002ic. The resolved Ha line has a P Cygni-type profile, clearly demonstrating the presence of a dense, slow-moving (~100 km s-1) outflow. We have additionally found a huge near-infrared excess, hitherto unseen in Type Ia supernovae. We argue that this is due to an infrared light-echo arising from the pre-existing dusty circumstellar medium. We deduce a circumstellar medium mass probably exceeding 0.3 Msolar produced by a mass-loss rate greater than several times 10-4 Msolar yr-1. For the progenitor, we favour a single-degenerate system where the companion is a post-asymptotic giant branch star. As a by-product of our optical data, we are able to provide a firm identification of the host galaxy of SN 2002ic.

Evidence for two-phase regions in BST thin films from capacitance-voltage data

The Curie-Weiss plots of reciprocal dielectric constant versus temperature, in Ba0.5Sr0.5TiO3 films grown onto SrRuO3 lower electrodes by pulsed-laser deposition, show two minima below film thicknesses of 280 nm. This double minima implies possible mixed phases in the thin films. A graphical plot of capacitance for decreasing dc voltage versus that of increasing dc voltage shows a well-defined triangular shape for both Pb(Zr0.4Ti0.6)O-3 and SrBi2Ta2O9 thin films. However, for a 175-nm-thick Ba0.5Sr0.5TiO3 thin film, the plot shows an overlapping of two triangles, suggesting mixed phases. This graphical method appears to be effective in detecting structural subtleties in ferroelectric capacitors.

Electrode field penetration: A new interpretation of tunneling currents in barium strontium titanate (BST) thin films

This paper shows that penetration of the applied electric field into the electrodes of a ferroelectric thin film capacitor produces both an interfacial capacitance and an effective mechanism for electron tunneling. The model predictions are compared with experimental results on Au-BST-SrRuO3 capacitors of varying thicknesses, and the agreement is excellent.

Liquid marble formation using hydrophobic powders

This work aims to investigate and quantitatively measure “liquid marble” phenomena using hydrophobic powders (granules). The hydrophobic powders based on a copper substrate were prepared by a silver deposition technique of particle sizes 9 µm, 20 µm and 320 µm and of contact angle with water approaching 160°. The hydrophobic powder poly-methylmethacralate (PMMA) particle size 42 µm and contact angle of 120° was also used to determine the effect of powder density on liquid marble stability. The experimental investigations indicated that for successful formation of liquid marbles a number of variables in addition to hydrophobicity need to be considered, namely: powder density; powder particle size; powder shape; liquid marble formation technique. It was found that liquid marbles were formed using all four powders to varying extents, with a low powder particle size forming more stable liquid marbles. In a series of gravimetric tests, adhered powder mass on liquid marbles was found to be directly proportional to the water droplet surface area. A more complete coverage of the water drops were found with PMMA powder than the hydrophobic granules. Moreover, a further procedure was developed to increase the mechanical strength of the liquid marble, by polymerising methylmethacrylate (MMA) on the surface of a PMMA powder – liquid marble, with the aim of maintaining water within a more robust PMMA – liquid marble shell. This technique may prove to be a novel way of encapsulating drug compounds, such as gentamicin sulphate, for PMMA bone cement.

SN 2008S: an electron-capture SN from a super-AGB progenitor?

We present comprehensive photometric and spectroscopic observations of the faint transient SN 2008S discovered in the nearby galaxy NGC 6946. SN 2008S exhibited slow photometric evolution and almost no spectral variability during the first nine months, implying a long photon diffusion time and a high-density circumstellar medium. Its bolometric luminosity (similar or equal to 10(41) erg s(-1) at peak) is low with respect to most core-collapse supernovae but is comparable to the faintest Type II-P events. Our quasi-bolometric light curve extends to 300 d and shows a tail phase decay rate consistent with that of Co-56. We propose that this is evidence for an explosion and formation of Ni-56 (0.0014 +/- 0.0003 M-circle dot). Spectra of SN 2008S show intense emission lines of H alpha, [Ca II] doublet and Ca II near-infrared (NIR) triplet, all without obvious P-Cygni absorption troughs. The large mid-infrared (MIR) flux detected shortly after explosion can be explained by a light echo from pre-existing dust. The late NIR flux excess is plausibly due to a combination of warm newly formed ejecta dust together with shock-heated dust in the circumstellar environment. We reassess the progenitor object detected previously in Spitzer archive images, supplementing this discussion with a model of the MIR spectral energy distribution. This supports the idea of a dusty, optically thick shell around SN 2008S with an inner radius of nearly 90 AU and outer radius of 450 AU, and an inferred heating source of 3000 K. The luminosity of the central star is L similar or equal to 10(4.6) L-circle dot. All the nearby progenitor dust was likely evaporated in the explosion leaving only the much older dust lying further out in the circumstellar environment. The combination of our long-term multiwavelength monitoring data and the evidence from the progenitor analysis leads us to support the scenario of a weak electron-capture supernova explosion in a super-asymptotic giant branch progenitor star (of initial mass 6-8 M-circle dot) embedded within a thick circumstellar gaseous envelope. We suggest that all of main properties of the electron-capture SN phenomenon are observed in SN 2008S and future observations may allow a definitive answer.