Analysis of Simvastatin using a Simple and Fast High Performance Liquid Chromatography-Ultra Violet Method: Development, Validation and Application in Solubility Studies

Purpose: To develop and validate an accurate, rapid and reproducible reversed-phase high performance liquid chromatography (RP-HPLC) analytical method for the lipid lowering drug, simvastatin, and to apply the developed method to study the solubility of the drug in various oils andsurfactants.Methods: Isocratic RP-HPLC system with a UV-vis detector, and a column with dimensions 4.6 mm x 150 mm and 5ì particle size, was employed. The mobile phase consisted of methanol and 0.01M KH2PO4 phosphate buffer (80:20) at pH 5.5 adjusted with phosphoric acid (2M) and pumped at a flow rate of 1 ml/min. Validation parameters, viz, limit of detection (LOD), limit of quantification (LOQ) linearity, accuracy, precision, and sensitivity, were established. Solubility study was performed in various oils and surfactants at 25°C and the developed HPLC method was applied to analyze all samples.Results: The developed HPLC method showed good linearity (R2 = 0.9958 ± 0.0040. The intra- and inter-day % accuracy was more than 98 %. LOQ and LOQ were 0.160 and 0.484 ìg/ml respectively. Simvastatin showed the highest solubility in sesame oil (15 mg/ml) and in Tween 80 (11 mg/ml) at 25oC.Conclusion: An accurate, rapid and robust HPLC-UV method has been developed, validated and applied successfully to determine the solubility of simvastatin in oils.Keywords: Simvastatin, Validation, Solubility, Sesame oil, Tween 80

Solubility and Permeability Studies of Aceclofenac in Different Oils

Purpose: To measure the extent of solubility of the lipophilic drug,   aceclofenac, in 13 oils as well as its in vitro permeability from these oils in order to develop optimized topical microemulsion and  microemulsion-based gel for improved bioavailability.Methods: UV spectrophotometeric method was used at the wavelength of 276 nm to measure the dissolved quantity of aceclofenac in each of the oils (almond oil, oleic acid, castor oil, paraffin oil, cinnamon oil, clove oil, canola oil, sesame oil, isopropyl myristate (ipm), sunflower oil, corn oil, coconuts oil and eucalyptus oil) at 25 °C. The in-vitro permeability of aceclofenac in each of these oils was determined at 32 ± 0.5 °C using Franz diffusion cell with phosphate buffer (pH 7.4) as medium with 0.45ì cellulose acetate membrane. The solubility and permeability of aceclofenac were compared with the hydroalcoholic solution of aceclofenac.Results: The highest solubility values of 9.153 and 8.560 mg/ml for  aceclofenac were obtained with almond oil and oleic acid, respectively (p < 0.05). However the solubility and permeability of aceclofenac in hydro-alcoholic solution were 150.65 mg/ml and 14.91± 0.05 ìg/cm2/h,  respectively. Aceclofenac also showed higher permeability values (1.45± 0.04 and 1.21 ± 0.06) in almond oil and oleic acid, respectively, than in the other oils (p < 0.05).Conclusion: These findings show that almond oil and oleic acid are  promising vehicles for aceclofenac as its enhanced solubility and  permeability in these vehicles are suggestive of improved bioavailability.Keywords: Aceclofenac, Almond oil, Solubility; Permeability, Oleic acid, Bioavailability

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Water management and crop production for food security in China: A review

Food security is a high priority issue on the Chinese political agenda. China's food security is challenged by several anthropogenic, sociopolitical and policy factors, including: population growth; urbanization and industrialization; land use changes and water scarcity; income growth and nutritional transition; and turbulence in global energy and food markets. Sustained growth in agricultural productivity and stable relations with global food suppliers are the twin anchors of food security. Shortfalls in domestic food production can take their toll on international food markets. Turbulence in global energy markets can affect food prices and supply costs, affecting food security and poverty. Policy safeguards are needed to shield food supply against such forces. China must make unremitting policy responses to address the loss of its fertile land for true progress towards the goal of national food security, by investing in infrastructure such as irrigation, drainage, storage, transport, and agricultural research and institutional reforms such as tenure security and land market liberalization. The links between water and other development-related sectors such as population, energy, food, and environment, and the interactions among them require reckoning, as they together will determine future food security and poverty reduction in China. Climate change is creating a new level of uncertainty in water governance, requiring accelerated research to avoid water-related stresses.Economic reform Poverty reduction Dietary changes Biofuels GM crops Investment

Effect of Trace Magnesium Additions on the Dynamic Recrystallization in Cast Alloy 825 after One-Hit Hot-Deformation

Alloy 825 is widely used in several industries, but its useful service life is limited by both mechanical properties and corrosion resistance. The current work explores the effect of the addition of magnesium on the recrystallization and mechanical behavior of alloy 825 under hot compression. Compression tests were performed under conditions representative of typical forming processes: temperatures between 1100 and 1250 °C and at strain rates of 0.1–10 s−1 to a true strain of 0.7. Microstructural evolution was characterized by electron backscattered diffraction. Dynamic recrystallization was found to be more prevalent under all test conditions in samples containing magnesium, but not in all cases of conventional alloy 825. The texture direction ⟨101⟩ was the dominant orientation parallel to the longitudinal direction of casting (also the direction in which the samples were compressed) in samples that contained magnesium under all test conditions, but not in any sample that did not contain magnesium. For all deformation conditions, the peak stress was approximately 10% lower in material with the addition of magnesium. Furthermore, the differences in the peak strain between different temperatures are approximately 85% smaller if magnesium is present. The average activation energy for hot deformation was calculated to be 430 kJ mol−1 with the addition of magnesium and 450 kJ mol−1 without magnesium. The average size of dynamically recrystallized grains in both alloys showed a power law relation with the Zener–Hollomon parameter, DD~Z−n, and the exponent of value, n, is found to be 0.12. These results can be used to design optimized compositions and thermomechanical treatments of alloy 825 to maximize the useful service life under current service conditions. No experiments were conducted to investigate the effects of such changes on the service life and such experiments should now be performed.QC 20210517</p

Transformation pathways and fate of engineered nanoparticles (ENPs) in distinct interactive environmental compartments: A review

The ever increasing production and use of nano-enabled commercial products release the massive amount of engineered nanoparticles (ENPs) in the environment. An increasing number of recent studies have shown the toxic effects of ENPs on different organisms, raising concerns over the nano-pollutants behavior and fate in the various environmental compartments. After the release of ENPs in the environment, ENPs interact with various components of the environment and undergoes dynamic transformation processes. This review focus on ENPs transformations in the various environmental compartments. The transformation processes of ENPs are interrelated to multiple environmental aspects. Physical, chemical and biological processes such as the homo- or hetero-agglomeration, dissolution/sedimentation, adsorption, oxidation, reduction, sulfidation, photochemically and biologically mediated reactions mainly occur in the environment consequently changes the mobility and bioavailability of ENPs. Physico-chemical characteristics of ENPs (particle size, surface area, zeta potential/surface charge, colloidal stability, and core-shell composition) and environmental conditions (pH, ionic strength, organic and inorganic colloids, temperature, etc.) are the most important parameters which regulated the ENPs environmental transformations. Meanwhile, in the environment, organisms encountered multiple transformed ENPs rather than the pristine nanomaterials due to their interactions with various environmental materials and other pollutants. Thus it is the utmost importance to study the behavior of transformed ENPs to understand their environmental fate, bioavailability, and mode of toxicity

Contrasting effects of biochar and hydrothermally treated coal gangue on leachability, bioavailability, speciation and accumulation of heavy metals by rapeseed in copper mine tailings

The purpose of this research was to examine the influence of hydrothermally treated coal gangue (HTCG) with and without biochar (BC) on the leaching, bioavailability, and redistribution of chemical fractions of heavy metals (HMs) in copper mine tailing (Cu-MT). An increase in pH, water holding capacity (WHC) and soil organic carbon (SOC) were observed due to the addition of BC in combination with raw coal gangue (RCG) and HTCG. A high Cu and other HMs concentration in pore water (PW) and amended Cu-MT were reduced by the combination of BC with RCG and/or HTCG, whereas individual application of RCG slightly increased the Cu, Cd, and Zn leaching and bioavailability, compared to the unamended Cu-MT. Sequential extractions results showed a reduction in the exchangeable fraction of Cu, Cd, Pb, and Zn and elevation in the residual fraction following the addition of BC-2% and BC-HTCG. However, individual application of RCG slightly increased the Cu, Cd, and Zn exchangeable fractions assessed by chemical extraction method. Rapeseed was grown for the following 45 days during which physiological parameters, metal uptake transfer rate (TR), bioconcentration factor (BCF), and translocation factor (TF) were measured after harvesting. In the case of plant biomass, no significant difference between applied amendments was observed for the fresh biomass (FBM) and dry biomass (DBM) of shoots and roots of rapeseed. However, BC-2% and BC-HTCG presented the lowest HMs uptake, TR, BCF (BCFroot and BCFshoot), and TF for Cu, Cd, Cr, Ni, Pb, and Zn in rapeseed among the other amendments compared to the unamended Cu -MT. Overall, these findings are indicative that using biochar in combination with RCG and/or HTCG led to a larger reduction in HMs leaching and bioavailability, due to their higher sorption capacity and could be a suitable remediation strategy for heavy metals in a Cu-MT