Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats

Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase

Carbapenems, 'last-resort' β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form. However, the New Delhi metallo-β-lactamase (NDM-1) can persist under conditions of metal depletion. NDM-1 is a lipidated protein that anchors to the outer membrane of Gram-negative bacteria. Membrane anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer-membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the bla[subscript NDM] gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies.Kinship Foundation. Searle Scholars ProgramMassachusetts Institute of Technology. Department of Chemistr

Landscape development at Lina myr fen, Eastern Gotland, 9000-2500 cal. yr BP

Using diatoms, pollen, and geochemistry, we explore human habitation around Lina myr, Gotland, in relation to shore displacement. Archeological evidence has shown that Lina myr was an important area for its prehistoric human inhabitants. We investigate if and when Lina myr was connected to the sea and could therefore have been part of an inland water system useful for transport. A chronology was based on 14C AMS dating of terrestrial macrofossils and bulk sediments with dates ranging between 9100 and 2360 cal. yr BP. The initiation of the Littorina transgression was dated to 8500 cal. yr BP. A twofold pattern for the maximum sub-phase of the Littorina Sea is suggested from 8100 to 7500 cal. yr BP and from 6500 to 6000 cal. yr BP. The onset of cultivation and grazing was indicated by the presence of Hordeum and Plantago lanceolata in the pollen record during the Late Neolithic, at about 4580 cal. yr BP. During this time sea level was relatively higher than today and the Lina myr basin was connected with the Littorina Sea, which it continued to be until isostatic uplift caused it to become isolated at about 3820 cal. yr BP. After about 3000 cal. yr BP, human-made landscape changes intensified, grasslands increased, and shrublands decreased. </p