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

Inhibition of Competence Development, Horizontal Gene Transfer and Virulence in Streptococcus pneumoniae by a Modified Competence Stimulating Peptide

Competence stimulating peptide (CSP) is a 17-amino acid peptide pheromone secreted by Streptococcus pneumoniae. Upon binding of CSP to its membrane-associated receptor kinase ComD, a cascade of signaling events is initiated, leading to activation of the competence regulon by the response regulator ComE. Genes encoding proteins that are involved in DNA uptake and transformation, as well as virulence, are upregulated. Previous studies have shown that disruption of key components in the competence regulon inhibits DNA transformation and attenuates virulence. Thus, synthetic analogues that competitively inhibit CSPs may serve as attractive drugs to control pneumococcal infection and to reduce horizontal gene transfer during infection. We performed amino acid substitutions on conserved amino acid residues of CSP1 in an effort to disable DNA transformation and to attenuate the virulence of S. pneumoniae. One of the mutated peptides, CSP1-E1A, inhibited development of competence in DNA transformation by outcompeting CSP1 in time and concentration-dependent manners. CSP1-E1A reduced the expression of pneumococcal virulence factors choline binding protein D (CbpD) and autolysin A (LytA) in vitro, and significantly reduced mouse mortality after lung infection. Furthermore, CSP1-E1A attenuated the acquisition of an antibiotic resistance gene and a capsule gene in vivo. Finally, we demonstrated that the strategy of using a peptide inhibitor is applicable to other CSP subtype, including CSP2. CSP1-E1A and CSP2-E1A were able to cross inhibit the induction of competence and DNA transformation in pneumococcal strains with incompatible ComD subtypes. These results demonstrate the applicability of generating competitive analogues of CSPs as drugs to control horizontal transfer of antibiotic resistance and virulence genes, and to attenuate virulence during infection by S. pneumoniae

Selected Letters of Ananda K. Coomaraswamy

Terlepas dari pengaruh unik A. K. Coomaraswamy di timur dan barat, sedikit yang diketahui tentang orang di balik tulisan tersebut. Coomaraswamy membenci tulisan otobiografi dan menganggapnya vulgar yang melayani keingintahuan yang tidak sah. Namun pria ini menulis ribuan surat, di setiap surat menjalin kontak pribadi yang intim dengan koresponden. Kata demi kata, kalimat demi kalimat, dengan ketelitian yang sangat tajam, dia mengikuti proses berpikir orang lain. Seperti yang dikatakan Eric Gill tentang dia: 'Kamu memukul lurus dan berdarah keras dan sering berdarah'.Surat-surat yang termasuk dalam jilid ini, yang diterbitkan untuk pertama kalinya, mengungkapkan keberadaan pria tanpa kompromi ini yang tidak percaya pada teori atau ideologi, politik atau filsafat. Dengan ketelitian ilmiah yang diperoleh melalui pelatihannya sebagai seorang ahli geologi, dikombinasikan dengan kepekaannya yang luar biasa, dia mengarahkan dirinya pada disiplin ilmu sejarah, filsafat, agama, seni dan kerajinan. Surat-surat itu ditulis kepada orang-orang sezaman, ilmuwan, Sansekerta, biksu dan penyair Buddha, dan termasuk orang-orang seperti Schweitzer, Eric Gill, Northov, Herman Goetz, Muirhead, Needham, George Sarton, dan banyak lainnya. Mereka mengungkapkan jangkauan pikiran yang luar biasa yang melintasi peradaban, budaya, bahasa, seni dan kerajinan, yang mencakup keseluruhan

Time-Dependent Ventilation Flows Driven by Opposing Wind and Buoyancy

We consider transient flow in a box containing an isolated buoyancy source, ventilated by a windward high-level opening and a leeward low-level opening, so that prevailing wind acts to oppose buoyancy-driven flow. Hunt & Linden (J. Fluid Mech., vol. 527, 2005, p. 27) demonstrated that two stable steady states can exist above a critical wind strength: buoyancy-driven displacement ventilation with a two-layer stratification and wind-driven mixing ventilation with the whole interior contaminated by buoyant fluid. We present two time-dependent models for this system: a nonlinear ordinary differential equation (ODE) model following Kaye & Hunt (J. Fluid Mech., vol. 520, 2004, p. 135), assuming ‘perfect’ vertical mixing of fluid within each layer, and a partial differential equation model assuming zero vertical mixing, following Germeles (J. Fluid Mech., vol. 71, 1975, p. 601)