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.

Hydrogel-Forming Microneedle Arrays Allow Detection of Drugs and Glucose In Vivo: Potential for Use in Diagnosis and Therapeutic Drug Monitoring

We describe, for the first time the use of hydrogel-forming microneedle (MN) arrays for minimally-invasive extraction and quantification of drug substances and glucose from skin in vitro and in vivo. MN prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) (11.1% w/w) and poly(ethyleneglycol) 10,000 daltons (5.6% w/w) and crosslinked by esterification swelled upon skin insertion by uptake of fluid. Post-removal, theophylline and caffeine were extracted from MN and determined using HPLC, with glucose quantified using a proprietary kit. In vitro studies using excised neonatal porcine skin bathed on the underside by physiologically-relevant analyte concentrations showed rapid (5 min) analyte uptake. For example, mean concentrations of 0.16 μg/mL and 0.85 μg/mL, respectively, were detected for the lowest (5 μg/mL) and highest (35 μg/mL) Franz cell concentrations of theophylline after 5 min insertion. A mean concentration of 0.10 μg/mL was obtained by extraction of MN inserted for 5 min into skin bathed with 5 μg/mL caffeine, while the mean concentration obtained by extraction of MN inserted into skin bathed with 15 μg/mL caffeine was 0.33 μg/mL. The mean detected glucose concentration after 5 min insertion into skin bathed with 4 mmol/L was 19.46 nmol/L. The highest theophylline concentration detected following extraction from a hydrogel-forming MN inserted for 1 h into the skin of a rat dosed orally with 10 mg/kg was of 0.363 μg/mL, whilst a maximum concentration of 0.063 μg/mL was detected following extraction from a MN inserted for 1 h into the skin of a rat dosed with 5 mg/kg theophylline. In human volunteers, the highest mean concentration of caffeine detected using MN was 91.31 μg/mL over the period from 1 to 2 h post-consumption of 100 mg Proplus® tablets. The highest mean blood glucose level was 7.89 nmol/L detected 1 h following ingestion of 75 g of glucose, while the highest mean glucose concentration extracted from MN was 4.29 nmol/L, detected after 3 hours skin insertion in human volunteers. Whilst not directly correlated, concentrations extracted from MN were clearly indicative of trends in blood in both rats and human volunteers. This work strongly illustrates the potential of hydrogel-forming MN in minimally-invasive patient monitoring and diagnosis. Further studies are now ongoing to reduce clinical insertion times and develop mathematical algorithms enabling determination of blood levels directly from MN measurements.

Water use and conservation at the environmental protection area of Brilhante, Santa Catarina - Brazil

Dissertação mest., Gestão da Água e da Costa, Universidade do Algarve, 2008

Effect of nitrogen and potassium fertilisation on vegetative growth and flowering of mature carob trees (Ceratonia siliqua): variations in leaf area index and water use indices

This work aimed to assess how potassium (K) and nitrogen (N) fertilisation may affect the use of precipitation in terms of vegetative and flowering response of 15-year-old carob trees during a 3-year experiment. A field trial was conducted in 1997, 1998 and 1999 in Algarve (Southern Portugal) in a calcareous soil. Four fertilisation treatments were tested: no fertiliser (control); 0.8 kg N/tree (N treatment); 1 kg K 2 O/tree (K treatment) and 0.8 kg N/tree plus 1 kg K 2 O/tree (NK treatment). No irrigation was applied during the experimental period. Branch length increments were measured every month throughout the growing season and inflorescence number was registered once per year. There was a strong seasonal effect on vegetative growth, since low levels of precipitation (115 mm) during October 1998–March 1999 suppressed the increment in branch length. N supplied to the trees (N and NK treatments) tended to increase water use indices in terms of vegetative growth. No response to K alone was observed in trees fertilised only with K. The number of inflorescences increased throughout the experimental period, particularly for N and NK treatments, and a reduction of the precipitation amount during April, May and June, may also enhance flowering. This knowledge could be important when making decisions concerning fertilisation under dry conditions. The results reported here indicate that tree growth (expressed as the branch growth) and flower production under dry-farming conditions, may be achieved by applying 0.8 kg of N (as ammonium nitrate) per tree during the growing season. However, N uptake and use depends on soil water availability.

The use of nanoparticles in soil and water remediation processes

Environmental nanoremediation of various contaminants has been reported in several recent studies. In this paper, the state of the art on the use of nanoparticles in soil and groundwater remediation processes is presented. There is a substantive body of evidence on the growing and successful application of nanoremediation for a diversity of soil and groundwater contamination contexts, particularly, for heavy metals, other inorganic contaminants, organic contaminants and emerging contaminants, as pharmaceutical and personal care products. This review confirms the competence of the use of nanoparticles in the remediation of contaminated media and the prevalent use of iron based nanoparticles.

Protease inhibitor from Moringa oleifera with potential for use as therapeutic drug and as seafood preservative

Protease inhibitors are well known to have several applications in medicine and biotechnology. Several plant sources are known to return potential protease inhibitors. In this study plants belonging to different families of Leguminosae, Malvaceae, Rutaceae, Graminae and Moringaceae were screened for the protease inhibitor. Among them Moringa oleifera, belonging to the family Moringaceae, recorded high level of protease inhibitor activity after ammonium sulfate fractionation. M. oleifera, which grows throughout most of the tropics and having several industrial and medicinal uses, was selected as a source of protease inhibitor since so far no reports were made on isolation of the protease inhibitor. Among the different parts of M. oleifera tested, the crude extract isolated from the mature leaves and seeds showed the highest level of inhibition against trypsin. Among the various extraction media evaluated, the crude extract prepared in phosphate buffer showed maximum recovery of the protease inhibitor. The protease inhibitor recorded high inhibitory activity toward the serine proteases thrombin, elastase, chymotrypsin and the cysteine

Survey of Agricultural Practices and Alternatives to Pesticide Use to Conserve Water Resources in the Mojanda Watershed, Ecuador

Agriculture in the Mojanda Watershed is facing rainfall reductions caused by climate change. Reductions of water availability in the Watershed are also due to constant extension of the agricultural activities into the páramo ecosystem above 3000m a.s.l., with this ecosystem having immanently important functions in the local water balance. The application of pesticides threatens the quality of water and with less precipitation contaminations will further concentrate in the outflow. To analyze problems associated with agricultural practices in the area a questionnaire about agricultural practices (28) was conducted and fields (20) were surveyed for pests and diseases with a focus on potatoes (Solanum tuberosum L.), tree tomatoes (Solanum betaceum Cav.) and peas (Pisum sativum L.). Potatoes were infected to a low degree with Phytophthora infestans and according to the farmers the Andean potato weevil (Premnotrypes spec.) caused biggest losses. To combat the weevil the soils are disinfected with toxic Carbofuran (WHO Class 1B). Tree tomatoes showed symptoms of various fungal diseases. Most important was Fusarium solani causing the branches to rot and Anthracnosis (Colletotrichum gloeosporioides) causing the fruits to rot. Fungicide applications were correspondingly high. Peas were only minorly affected by Ascochyta blight (Mycosphaerella pinodes) and a root rot. Overall 19 active ingredients were applied of which fungicide Mancozeb (WHO class table 5) and insecticide Carbofuran (WHO Class 1B) were applied the most. Approved IPM methods are advised to reduce pesticide use. For tree tomatoes regular cutting of branches infected with F. solani and regular collection and disposal of infected fruits with Anthracnosis are advised. For potatoes plastic barriers around the fields prevent the Andean potato weevil from laying eggs thus reducing infestation with the larvae in the tubers. Local bioinsecticide “Biol” seems effective and without harm to the environment, although not used by many farmers. Organic fertilization promises to restore decreasing soil fertility, water holding capacity and reduce erosion. The here presented alternatives and strategies to reduce pesticide use pose an opportunity to preserve the water resources of the region.

Effects of changing water availability on land use in irrigated mountain oases of Al Jabal Al Akhdar, northern Oman

In Oman, during the last three decades, agricultural water use and groundwater extraction has dramatically increased to meet the needs of a rapidly growing population and major changes in lifestyle. This has triggered agricultural land-use changes which have been poorly investigated. In view of this our study aimed at analysing patterns of shortterm land-use changes (2007-2009) in the five irrigated mountain oases of Ash Sharayjah, Al’Ayn, Al’Aqr, Qasha’ and Masayrat ar Ruwajah situated in the northern Oman Hajar mountains of Al Jabal Al Akhdar where competitive uses of irrigation water are particularly apparent. Comprehensive GIS-based field surveys were conducted over three years to record changes in terrace use in these five oases where farmers have traditionally adapted to rain-derived variations of irrigation water supply, e.g. by leaving agricultural terraces of annual crops uncultivated in drought years. Results show that the area occupied with field crops decreased in the dry years of 2008 and 2009 for all oases. In Ash Sharayjah, terrace areas grown with field crops declined from 4.7 ha (32.4 % of total terrace area) in 2007 to 3.1 ha (21.6 %) in 2008 and 3.0 ha (20.5 %) in 2009. Similarly, the area proportion of field crops shrunk in Al’Ayn, Qasha’ and Masayrat from 35.2, 36.3 and 49.6 % in 2007 to 19.8, 8.5 and 41.3 % in 2009, respectively. In Al’Aqr, the area of field crops slightly increased from 0.3 ha (17.0 %) in 2007 to 0.7 (39.1 %) in 2008, and decreased to 0.5 ha (28.8 %) in 2009. During the same period annual dry matter yields of the cash crop garlic in Ash Sharayjah increased from 16.3 t ha-1 in 2007 to 19.8 t ha-1 in 2008 and 18.3 t ha-1 in 2009, while the same crop yielded only 0.4, 1.6 and 1.1 t ha-1 in Masayrat. In 2009, the total estimated agricultural area of the new town of Sayh Qatanah above the five oases was around 13.5 ha. Our results suggest that scarcity of irrigation water as a result of low precipitation and increased irrigation and home water consumption in the new urban settlements above the five oases have led to major shifts in the land-use pattern and increasingly threaten the centuries-long tradition and drought-resilience of agriculture in the oases of the studied watershed.

How we use water.

Permite al lector apreciar cómo se usan las riquezas naturales y como punto de partida para el aprendizaje de las propiedades y sobre cuáles son algunos de los usos del agua: para beber, lavar, jugar, cultivar. Para la energía, el transporte, la refrigeración. De donde viene. Cómo se recicla. Por qué no utilizar agua en lugar de gasolina. El agua y el medio ambiente. Describe la forma en que no se debe utilizar. Tiene glosario, bibliografía y direcciones de Internet.

Contemporary social variations in household water use, management strategies and awareness under conditions of 'water stress': the case of Greater Amman Jordan

One of the distinctive characteristics of the water supply system of Greater Amman, the capital of Jordan, is that it has been based on a regime of rationing since 1987, with households receiving water once a week for various durations. This reflects the fact that while Amman's recent growth has been phenomenal, Jordan is one of the ten most water-scarce nations on earth. Amman is highly polarised socio-economically, and by means of household surveys conducted in both high- and low-income divisions of the city, the aim has been to provide detailed empirical evidence concerning the storage and use if water, the strategies used by households to manage water and overall satisfactions with water supply issues, looking specifically at issues of social equity. The analysis demonstrates the social costs of water rationing and consequent household management to be high, as well as emphasising that issues of water quality are of central importance to all consumers.

Over-parameterised, uncertain 'mathematical marionettes' - How can we best use catchment water quality models? An example of an 80-year catchment-scale nutrient balance

The Integrated Catchment Model of Nitrogen (INCA-N) was applied to the River Lambourn, a Chalk river-system in southern England. The model's abilities to simulate the long-term trend and seasonal patterns in observed stream water nitrate concentrations from 1920 to 2003 were tested. This is the first time a semi-distributed, daily time-step model has been applied to simulate such a long time period and then used to calculate detailed catchment nutrient budgets which span the conversion of pasture to arable during the late 1930s and 1940s. Thus, this work goes beyond source apportionment and looks to demonstrate how such simulations can be used to assess the state of the catchment and develop an understanding of system behaviour. The mass-balance results from 1921, 1922, 1991, 2001 and 2002 are presented and those for 1991 are compared to other modelled and literature values of loads associated with nitrogen soil processes and export. The variations highlighted the problem of comparing modelled fluxes with point measurements but proved useful for identifying the most poorly understood inputs and processes thereby providing an assessment of input data and model structural uncertainty. The modelled terrestrial and instream mass-balances also highlight the importance of the hydrological conditions in pollutant transport. Between 1922 and 2002, increased inputs of nitrogen from fertiliser, livestock and deposition have altered the nitrogen balance with a shift from possible reduction in soil fertility but little environmental impact in 1922, to a situation of nitrogen accumulation in the soil, groundwater and instream biota in 2002. In 1922 and 2002 it was estimated that approximately 2 and 18 kg N ha(-1) yr(-1) respectively were exported from the land to the stream. The utility of the approach and further considerations for the best use of models are discussed. (C) 2008 Elsevier B.V. All rights reserved.

Over-parameterised, uncertain 'mathematical marionettes' - How can we best use catchment water quality models? An example of an 80-year catchment-scale nutrient balance

The Integrated Catchment Model of Nitrogen (INCA-N) was applied to the River Lambourn, a Chalk river-system in southern England. The model's abilities to simulate the long-term trend and seasonal patterns in observed stream water nitrate concentrations from 1920 to 2003 were tested. This is the first time a semi-distributed, daily time-step model has been applied to simulate such a long time period and then used to calculate detailed catchment nutrient budgets which span the conversion of pasture to arable during the late 1930s and 1940s. Thus, this work goes beyond source apportionment and looks to demonstrate how such simulations can be used to assess the state of the catchment and develop an understanding of system behaviour. The mass-balance results from 1921, 1922, 1991, 2001 and 2002 are presented and those for 1991 are compared to other modelled and literature values of loads associated with nitrogen soil processes and export. The variations highlighted the problem of comparing modelled fluxes with point measurements but proved useful for identifying the most poorly understood inputs and processes thereby providing an assessment of input data and model structural uncertainty. The modelled terrestrial and instream mass-balances also highlight the importance of the hydrological conditions in pollutant transport. Between 1922 and 2002, increased inputs of nitrogen from fertiliser, livestock and deposition have altered the nitrogen balance with a shift from possible reduction in soil fertility but little environmental impact in 1922, to a situation of nitrogen accumulation in the soil, groundwater and instream biota in 2002. In 1922 and 2002 it was estimated that approximately 2 and 18 kg N ha(-1) yr(-1) respectively were exported from the land to the stream. The utility of the approach and further considerations for the best use of models are discussed. (C) 2008 Elsevier B.V. All rights reserved.