Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Starch granule surface characterization using novel surface analytical and imaging techniques

National audienc

Investigating the coating dependent release mechanism of a pulsatile capsule using NMR microscopy

Chronopharmaceutical capsules, ethylcellulose-coated to prevent water ingress, exhibited clearly different release characteristics when coated by organic or aqueous processes. Organic-coated capsules produced a delayed pulse release, whereas aqueous-coated capsules exhibited less delayed and more erratic release behaviour. Nuclear magnetic resonance microscopy was used to elucidate the internal mechanisms underlying this behaviour by studying the routes of internal water transport and the timescale and sequence of events leading to the pulse. Images showed that the seal between the shell and the tablet plug is a key route of water penetration in these dosage forms. There is evidence for a more efficient seal in the organic-coated capsule, and although some hydration of the contents was evident, erosion of the tablet plug is most probably the controlling factor in timed release. The premature failure of the aqueous-coated capsule appears to be a result of rapid influx of water between plug and capsule with hydration of the low substituted hydroxypropylcellulose expulsion agent. As a result of this, the tablet plug remains intact, but appears unable to be ejected. The resulting significant pressure build-up causes premature release by distortion and splitting of the capsule shell. These events may be aided by a weakening of the aqueous-coated gelatin shell by hydration from the inside, and at the mouth of the capsule where previous electron microscope studies have shown incomplete coating of the inside by the aqueous process

The effects of aggressive mitigation on steric sea level rise and sea ice changes

International audienceWith an increasing political focus on limiting global warming to less than 2 °C above pre-industrial levels it is vital to understand the consequences of these targets on key parts of the climate system. Here, we focus on changes in sea level and sea ice, comparing twenty-first century projections with increased greenhouse gas concentrations (using the mid-range IPCC A1B emissions scenario) with those under a mitigation scenario with large reductions in emissions (the E1 scenario). At the end of the twenty-first century, the global mean steric sea level rise is reduced by about a third in the mitigation scenario compared with the A1B scenario. Changes in surface air temperature are found to be poorly correlated with steric sea level changes. While the projected decreases in sea ice extent during the first half of the twenty-first century are independent of the season or scenario, especially in the Arctic, the seasonal cycle of sea ice extent is amplified. By the end of the century the Arctic becomes sea ice free in September in the A1B scenario in most models. In the mitigation scenario the ice does not disappear in the majority of models, but is reduced by 42 % of the present September extent. Results for Antarctic sea ice changes reveal large initial biases in the models and a significant correlation between projected changes and the initial extent. This latter result highlights the necessity for further refinements in Antarctic sea ice modelling for more reliable projections of future sea ice. © 2012 The Author(s)

Erratum to: Climate change under aggressive mitigation: The ENSEMBLES multi-model experiment (Clim Dyn, (2011), 10.1007/s00382-011-1005-5)

International audienceUnfortunately, in the aforementioned contribution, Table 2 of this paper erroneously reported two separate rows of data for the BCM-C model for both the A1B and E1 scenarios, only one of which was correct in each case. The lower of the two rows of data for each scenario (i.e. those corresponding to T changes of 2.44 K for A1B and 1.18 K for E1) contained correct data. The upper rows of data reported (i.e. those corresponding to T changes of 2.65 K for A1B and 1.38 for E1) contained some errors and should not have appeared. A corrected version of Table 2 appears below