The Use of High Surface Area Silica and Supercritical Carbon Dioxide to Enhance Solubility of Poorly Water-Soluble Drugs

Purpose Poor water-solubility of BCS class II drugs can limit their commercialization because of reduced oral bioavailability. It has been reported that loading of drug by adsorption onto porous silica would enhance drug solubility due to the increased surface area available for solvent diffusion. In this work, solid dispersions are formed using supercritical carbon dioxide (scCO2). The aim of this research was to characterise the solid-state properties of scCO2 dispersion and to investigate the impact of altering scCO2 processing conditions on final amorphous product performance that could lead to enhancement of drug dissolution rate for BCS class II drugs. Methods Indomethacin (IND) was purchased from Sigma-Aldrich (Dorset, UK) and was used as a model drug with two grades of high surface area silica (average particle sizes 3&[micro] and 7&[micro]), which were obtained directly from Grace-Davison (Germany). Material crystallinity was evaluated using powder X-ray diffraction (PXRD, Rigaku™, miniflex II, Japan) and high-speed differential scanning calorimetry (Hyper-DSC 8000, Perkin Elmer, USA). Materials were placed in a high-pressure vessel consisting of a CO2 cylinder, a Thar™ Technologies P50 high-pressure pump and a 750 ml high-pressure vessel (Thar, USA). Physical mixtures were exposed to CO2 gas above its critical conditions. SEM imaging and elemental analysis were conducted using a Jeol 6500 FEGSEM (Advanced MicroBeam Inc., Austria). Drug release was examined using USP type II dissolution tester (Caleva™, UK). Results The two grades of silica were found to be amorphous using PXRD and Hyper-DSC. Using PXRD, it was shown that an increase in incubation time and pressure resulted in a decrease in the crystalline content. Drug release profiles from the two different silica formulations prepared under the same conditions are shown in Figure 1. It was found that there was a significant enhancement in drug release, which was influenced, by silica type and other experiment conditions such as temperature, pressure and exposure time. SEM imaging and elemental analysis showed drug deposited inside silica pores as well as on the outer surface. Conclusion This project has shown that silica carrier platforms may be used as an alternative approach to generating polymeric solid dispersions of amorphous drugs exhibiting enhanced solubility.

Synthesis of spherical ultra-high-surface-area monodisperse amphipathic polymer sponges in the low-micrometer size range

Spherical, ultra-high specific surface area monodisperse polymer particles with diameters in the low micrometer size range are disclosed for the first time. The polymer particles are able to sorb significant levels of both hydrocarbon solvents and water, acting in effect as amphipathic micro-sponges. Exciting possibilities for exploitation of the particles in chromatography, diagnostics, sensors, delivery vehicles and catalysis are suggested.

Leatherback turtles satellite-tagged in European waters

The North Atlantic is considered a stronghold for the critically endangered leatherback sea turtle. However, limited information exists regarding the movements of individuals to and from the seas off Europe's northwesterly fringe, an area where featherbacks have been historically sighted for the past 200 yr. Here, we used satellite telemetry to record the movements and behaviour of 2 individuals bycaught in fisheries off the southwest coast of Ireland. The turtle T1 (tagged 1 September 2005; female; tracked 375 d) immediately travelled south via Madeira and the Canaries, before residing in West African waters for 3 mo. In spring, T1 migrated north towards Newfoundland where transmissions ceased. T2 (29 June 2006; male; 233 d) travelled south for a short period before spending 66 d west of the Bay of Biscay, an area previously asserted as a high-use area for leatherbacks. This prolonged high latitude summer residence corresponded with a mesoscale feature evident from satellite imagery, with the implication that this turtle had found a rich feeding site. A marked change in dive behaviour was apparent as the turtle exited this feature and provided useful insights on leatherback diving behaviour. T2 headed south in October 2006, and performed the deepest-ever dive recorded by a reptile (1280 m) southwest of Cape Verde. Unlike T1, T2 swam southwest towards Brazil before approaching the major nesting beaches of French Guiana and Surinam. Importantly, these tracks document the movement of leatherbacks from one of the remotest foraging grounds in the North Atlantic. © Inter-Research 2008.

Paracetamol-Loaded Poly(ε-caprolactone) Layered Silicate Nanocomposites

The work described in this paper demonstrates a combined novel approach to the preparation of drug loaded poly(e-caprolactone) layered silicate nanocomposites using hot melt extrusion, a continuous process in contrast to the normal batch type processing used to prepare polymeric drug delivery systems, and most significantly the use of high surface area, large aspect ratio inorganic nanoplatelets to retard drug release. The methodology and results described in this article are significant and could equally be applied to the controlled/retarded release of any bio-active molecule (pharmaceutical, nutraceutical, protein, DNA/iRNA, anti-microbial, anti-coagulant, etc.) from biopolymers and the production of medical devices from such composite materials.

Average household income, crime, and smoking behaviour in a local area: The Finnish 10-Town study

Social environments, like neighbourhoods, are increasingly recognised as determinants of health. While several studies have reported an association of low neighbourhood socio-economic status with morbidity, mortality and health risk behaviour, little is known of the health effects of neighbourhood crime rates. Using the ongoing 10-Town study in Finland, we examined the relations of average household income and crime rate measured at the local area level, with smoking status and intensity by linking census data of local area characteristics from 181 postal zip codes to survey responses to smoking behaviour in a cohort of 23,008 municipal employees. Gender-stratified multilevel analyses adjusted for age and individual occupational status revealed an association between low local area income rate and current smoking. High local area crime rate was also associated with current smoking. Both local area characteristics were strongly associated with smoking intensity. Among ever-smokers, being an ex-smoker was less likely among residents in areas with low average household income and a high crime rate. In the fully adjusted model, the association between local area income and smoking behaviour among women was substantially explained by the area-level crime rate. This study extends our knowledge of potential pathways through which social environmental factors may affect health. (c) 2007 Elsevier Ltd. All rights reserved.

An ionic liquid process for mercury removal from natural gas

Efficient scrubbing of mercury vapour from natural gas streams has been demonstrated both in the laboratory and on an industrial scale, using chlorocuprate(ii) ionic liquids impregnated on high surface area porous solid supports, resulting in the effective removal of mercury vapour from natural gas streams. This material has been commercialised for use within the petroleum gas production industry, and has currently been running continuously for three years on a natural gas plant in Malaysia. Here we report on the chemistry underlying this process, and demonstrate the transfer of this technology from gram to ton scale.

Carbons, Ionic Liquids, and Quinones for Electrochemical Capacitors

Carbons are the main electrode materials used in supercapacitors, which are electrochemical energy storage devices with high power densities and long cycling lifetimes. However, increasing their energy density capacity will improve their potential for commercial implementation.
In this regard, the use of high surface area carbons and high voltage electrolytes are well known strategies to increase the attainable energy density, and lately ionic liquids have been explored as promising alternatives to current state of the art acetonitrile-based electrolytes. Also, in terms of safety and sustainability ionic liquids are attractive electrolyte materials for supercapacitors. In addition, it has been shown that the matching of the carbon pore size with the electrolyte ion size further increases the attainable electrochemical double layer (ECDL) capacitance and energy density.
The use of pseudocapacitive reactions can significantly increase the attainable energy density, and quinonic-based materials offer a potentially sustainable and cost effective research avenue for both the electrode and the electrolyte.
This perspective will provide an overview of the current state of the art research on supercapacitors based on combinations of carbons, ionic liquids and quinonic compounds, highlighting performances and challenges and discussing possible future research avenues. In this regard, current interest is mainly focused on strategies which may ultimately lead to commercially competitive sustainable high performance supercapacitors for different applications including those requiring mechanical flexibility and biocompatibility.

HETEROGENEOUS REDOX CATALYSIS - A NOVEL ROUTE FOR REMOVING BROMATE IONS FROM WATER

The oxidation of water to oxygen by bromate ions is mediated by the heterogeneous redox catalyst ruthenium-Adams, a high surface area and very stable form of ruthenium(IV) oxide. The initial kinetics of catalysis are investigated as a function of [BrO3-], [Ru-Adams], temperature and [anion], where ''anion'' = ClO4- Cl- or Br-. An electrochemical model of heterogeneous redox catalysis, in which the two participating redox couples are both electrochemically irreversible, is used to interpret most of the kinetic data. The observed inhibition of the initial rate of the redox reaction by Cl- and, especially, Br- ions is tentatively attributed to competitive adsorption. In the presence of organic species, such as methanol, ethanol and propan-1-ol, which are more easily oxidised than water by bromate ions, the rate of BrO3- ion reduction is significantly faster, i.e. ca 24-34 times.

PREVENTION OF INFECTION AFTER SPLENECTOMY - WHAT PRECAUTIONS ARE REQUIRED

Removal of the spleen presents a lifelong risk of infection, in particular the syndrome of overwhelming postsplenectomy sepsis. Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitides are the most common organisms involved, but malaria, babesiosis and DF-2 also create a problem. Immunisation with pneumococcal vaccine, H. influenzae type b vaccine, influenza vaccine and, if in a high risk area, meningococcal vaccine is recommended. Lifelong phenoxymethylpenicillin 250mg twice daily is also advised, especially in high risk groups such as children and immunocompromised patients. If patients are unwilling to take medicine lifelong, or are unlikely to comply, an antibiotic supply should be made available at all times and administration should commence at the first sign of illness.

Assessing the occupational risk of dust particles in the Kenyan tanning industry using rapid image processing and microscopy techniques

The purpose of this study was to investigate the occupational hazards within the tanning industry caused by contaminated dust. A qualitative assessment of the risk of human exposure to dust was made throughout a commercial Kenyan tannery. Using this information, high-risk points in the processing line were identified and dust sampling regimes developed. An optical set-up using microscopy and digital imaging techniques was used to determine dust particle numbers and size distributions. The results showed that chemical handling was the most hazardous (12 mg m(-3)). A Monte Carlo method was used to estimate the concentration of the dust in the air throughout the tannery during an 8 h working day. This showed that the high-risk area of the tannery was associated with mean concentrations of dust greater than the UK Statutory Instrument 2002 No. 2677. stipulated limits (exceeding 10 mg m(-3) (Inhalable dust limits) and 4 mg m(-3) (Respirable dust limits). This therefore has implications in terms of provision of personal protective equipment (PPE) to the tannery workers for the mitigation of occupational risk.

Sulfated zirconia in SBA-15 structures with strong Bronsted acidity as observed by H-1 MAS NMR spectroscopy

In order to prepare high surface area highly acidic catalysts, different weight loadings of ZrO2 were incorporated in the SBA-15 structures which are subsequently sulfated by treating in 0.25 M H2SO4. The catalysts were characterized by means of TEM, XRD, N-2 adsorption, and H-1 MAS NMR. Bronsted type acidities of sulfated zirconia included SBA-15 materials were identified by a sharp H-1 MAS NMR line at 10.6 ppm. The highest acidity was obtained in the 25 mol% ZrO2 included SBA-15 catalyst with a BET surface area of 246 m(2)/g.

Psychotropic medications and the transition into care:a national data linkage study

Objectives
To determine whether excessive and often inappropriate or dangerous psychotropic drug dispensing to older adults is unique to care homes or is a continuation of community treatment.

Design
Population-based data-linkage study using prescription drug information.

Setting
Northern Ireland's national prescribing database and care home information from the national inspectorate.

Participants
Two hundred fifty thousand six hundred seventeen individuals aged 65 and older.

Measurements
Prescription information was extracted for all psychotropic drugs included in the British National Formulary (BNF) categories 4.1.1, 4.1.2, and 4.2.2 (hypnotics, anxiolytics, and antipsychotics) dispensed over the study period. Repeated cross-sectional analysis was used to monitor changes in psychotropic drug dispensing over time.

Results
Psychotropic drug use was higher in care homes than the community; 20.3% of those in care homes were dispensed an antipsychotic in January 2009, compared with 1.1% of those in the community. People who entered care had higher use of psychotropic medications before entry than those who did not enter care, but this increased sharply in the month of admission and continued to rise. Antipsychotic drug dispensing increased from 8.2% before entry to 18.6% after entering care (risk ratio (RR) = 2.26, 95% confidence interval (CI)=1.96–2.59) and hypnotic drug dispensing from 14.8% to 26.3% (RR=1.78, 95% CI=1.61–1.96).

Conclusion
A continuation of high use before entry cannot wholly explain the higher dispensing of psychotropic drugs to individuals in care homes. Although drug dispensing is high in older people in the community, it increases dramatically on entry to care. Routine medicine reviews are necessary in older people and are especially important during transitions of care.

Development of a slurry continuous flow reactor for photocatalytic treatment of industrial waste water

The water treatment capability of a novel photocatalytic slurry reactor was investigated using methylene blue (MB) as a model pollutant in an aqueous suspension. A pellet TiO ₂ catalyst was employed and this freed the system from the need of filtration of catalyst following photocatalysis. This configuration combines the high surface area contact of catalyst with pollutant of the slurry reactor and also offers a high illumination of catalyst by its unique array of weir-like baffles. In this work, the batch adsorption of MB from aqueous solution (10μM) onto the TiO ₂ catalyst was studied, adsorption isotherms and kinetics were determined from the experimental data. Complete degradation of MB was achieved within 60 min illumination with various loadings of catalyst (30-200 g L ^-1). A modest catalyst loading (30 g L ^-1) achieved 98% degradation within 60 min of irradiation. Experimental results indicate that this novel reactor configuration has a high effective mass transfer rate and UV light penetration characteristics.