Cocrystal habit engineering to improve drug dissolution and alter derived powder properties

YesObjectives: Cocrystallization of sulfadimidine (SDM) with suitable coformers, such as 4-aminosalicylic acid (4-ASA), combined with changes in the crystal habit can favourably alter its physicochemical properties. The aim of this work was to engineer SDM:4-ASA cocrystals with different habits in order to investigate the effect on dissolution, and the derived powder properties of flow and compaction. Methods: Cocrystals were prepared in a 1:1 molar ratio by solvent evaporation using ethanol (habit I) or acetone (habit II), solvent evaporation followed by grinding (habit III) and spray-drying (habit IV). Key findings: Powder X-ray diffraction showed Bragg peak position was the same in all the solid products. The peak intensity varied, indicating different preferred crystal orientation confirmed by SEM micrographs: large prismatic crystals (habit I), large plate-like crystals (habit II), small cube-like crystals (habit III) and microspheres (habit IV). The habit III exhibited the fasted dissolution rate; however, it underwent a polymorphic transition during dissolution. Habits I and IV exhibited the highest Carr’s compressibility index, indicating poor flowability. However, habits II and III demonstrated improved flow. Spray drying resulted in cocrystals with improved compaction properties. Conclusions: Even for cocrystals with poor pharmaceutical characteristics, a habit can be engineered to alter the dissolution, flowability and compaction behavior.Science Foundation Ireland. Grant Number: SFI/12/RC/227

Analysis of linear long-term trend of aerosol optical thickness derived from SeaWiFS using BAER over Europe and South China

The main purposes of the present paper are not only to investigate linear long-term trends of Aerosol Optical Thickness (AOT) at 443 and 555 nm over regions in Europe and South China, but also to show the uncertainty caused by cloud disturbance in the trend analysis of cloud-free aerosol. These research areas are the densely urbanised and often highly polluted regions. The study uses the Bremen AErosol Retrieval (BAER) and Sea-viewing Wide Field-of-view Sensor (SeaWiFS) data for AOT retrievals in the specified regions from October 1997 to May 2008. In order to validate the individually retrieved AOTs and the corresponding trends, AErosol RObotic NETwork (AERONET) level 2.0 data have been used. The retrieved AOTs were in good agreement with those of AERONET (0.79 ≤ <i>R</i> ≤ 0.88, 0.08 ≤ RMSD ≤ 0.13). The contamination of the aerosol retrievals and/or AERONET observations by thin clouds can significantly degrade the AOT and lead to statistically non-representative monthly-means, especially during cloudy seasons. Therefore an inter-correction method has been developed and applied. The "corrected" trends for both BAER SeaWiFS and AERONET AOT were similar and showed in average a relative difference of ∼25.19%. In general terms, negative trends (decrease of aerosol loading) were mainly observed over European regions, with magnitudes up to −0.00453 and −0.00484 yr<sup>−1</sup> at 443 and 555 nm, respectively. In contrast, the trend in Pearl River Delta was positive, most likely attributed to rapid urbanization and industrialization. The magnitudes of AOT increased by +0.00761 and +0.00625 yr<sup>−1</sup> respectively at 443 and 555 nm

Spin-dynamics simulations of the triangular antiferromagnetic XY model

Using Monte Carlo and spin-dynamics methods, we have investigated the dynamic behavior of the classical, antiferromagnetic XY model on a triangular lattice with linear sizes $L \leq 300$. The temporal evolutions of spin configurations were obtained by solving numerically the coupled equations of motion for each spin using fourth-order Suzuki-Trotter decompositions of exponential operators. From space- and time-displaced spin-spin correlation functions and their space-time Fourier transforms we obtained the dynamic structure factor $S({\bf q},w)$ for momentum ${\bf q}$ and frequency $\omega$. Below $T_{KT}$(Kosterlitz-Thouless transition), both the in-plane ($S^{xx}$) and the out-of-plane ($S^{zz}$) components of $S({\bf q},\omega)$ exhibit very strong and sharp spin-wave peaks. Well above $T_{KT}$, $S^{xx}$ and $S^{zz}$ apparently display a central peak, and spin-wave signatures are still seen in $S^{zz}$. In addition, we also observed an almost dispersionless domain-wall peak at high $\omega$ below $T_{c}$(Ising transition), where long-range order appears in the staggered chirality. Above $T_{c}$, the domain-wall peak disappears for all $q$. The lineshape of these peaks is captured reasonably well by a Lorentzian form. Using a dynamic finite-size scaling theory, we determined the dynamic critical exponent $z$ = 1.002(3). We found that our results demonstrate the consistency of the dynamic finite-size scaling theory for the characteristic frequeny $\omega_{m}$ and the dynamic structure factor $S({\bf q},\omega)$ itself.Comment: 8 pages, RevTex, 10 figures, submitted to PR

A 1.4 deg^2 blind survey for C II], C III] and C IV at z ~ 0.7-1.5 - II. Luminosity functions and cosmic average line ratios

Article / Letter to editorSterrewach

BB flavour tagging using charm decays at the LHCb experiment

An algorithm is described for tagging the flavour content at production of neutral $B$ mesons in the LHCb experiment. The algorithm exploits the correlation of the flavour of a $B$ meson with the charge of a reconstructed secondary charm hadron from the decay of the other $b$ hadron produced in the proton-proton collision. Charm hadron candidates are identified in a number of fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is calibrated on the self-tagged decay modes $B^+ \to J/\psi \, K^+$ and $B^0 \to J/\psi \, K^{*0}$ using $3.0\mathrm{\,fb}^{-1}$ of data collected by the LHCb experiment at $pp$ centre-of-mass energies of $7\mathrm{\,TeV}$ and $8\mathrm{\,TeV}$. Its tagging power on these samples of $B \to J/\psi \, X$ decays is $(0.30 \pm 0.01 \pm 0.01) \%$.Comment: All figures and tables, along with any supplementary material and additional information, are available at http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm

Evidence for the strangeness-changing weak decay Ξb−→Λb0π−\Xi_b^-\to\Lambda_b^0\pi^-

Using a $pp$ collision data sample corresponding to an integrated luminosity of 3.0~fb$^{-1}$, collected by the LHCb detector, we present the first search for the strangeness-changing weak decay $\Xi_b^-\to\Lambda_b^0\pi^-$. No $b$ hadron decay of this type has been seen before. A signal for this decay, corresponding to a significance of 3.2 standard deviations, is reported. The relative rate is measured to be ${{f_{\Xi_b^-}}\over{f_{\Lambda_b^0}}}{\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) = (5.7\pm1.8^{+0.8}_{-0.9})\times10^{-4}$, where $f_{\Xi_b^-}$ and $f_{\Lambda_b^0}$ are the $b\to\Xi_b^-$ and $b\to\Lambda_b^0$ fragmentation fractions, and ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ is the branching fraction. Assuming $f_{\Xi_b^-}/f_{\Lambda_b^0}$ is bounded between 0.1 and 0.3, the branching fraction ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ would lie in the range from $(0.57\pm0.21)\%$ to $(0.19\pm0.07)\%$.Comment: 7 pages, 2 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm

Novel enabling strategies for oral peptide delivery

Oral peptide delivery market grows with a double-digit annual rate fueled by advancements in drug delivery and the increasing prevalence of chronic diseases. Nonetheless, the successful delivery of peptides through the gastrointestinal tract encounters numerous challenges, such as enzymatic degradation, poor stability, limited permeability, and low oral bioavailability. This review examines the challenges associated with oral peptide delivery and providing a novel perspective into potential strategies to enable oral peptide therapeutics, highlighting the promising roles of 3D printing technology, hydrophobic ion pairing, and self-nano emulsifying drug delivery systems (SNEDDS)

Absolute luminosity measurements with the LHCb detector at the LHC

Absolute luminosity measurements are of general interest for colliding-beam experiments at storage rings. These measurements are necessary to determine the absolute cross-sections of reaction processes and are valuable to quantify the performance of the accelerator. Using data taken in 2010, LHCb has applied two methods to determine the absolute scale of its luminosity measurements for proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In addition to the classic "van der Meer scan" method a novel technique has been developed which makes use of direct imaging of the individual beams using beam-gas and beam-beam interactions. This beam imaging method is made possible by the high resolution of the LHCb vertex detector and the close proximity of the detector to the beams, and allows beam parameters such as positions, angles and widths to be determined. The results of the two methods have comparable precision and are in good agreement. Combining the two methods, an overall precision of 3.5% in the absolute luminosity determination is reached. The techniques used to transport the absolute luminosity calibration to the full 2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6, 9 and 10 and corresponding explanation in the tex

Absolute luminosity measurements with the LHCb detector at the LHC

Absolute luminosity measurements are of general interest for colliding-beam experiments at storage rings. These measurements are necessary to determine the absolute cross-sections of reaction processes and are valuable to quantify the performance of the accelerator. Using data taken in 2010, LHCb has applied two methods to determine the absolute scale of its luminosity measurements for proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In addition to the classic "van der Meer scan" method a novel technique has been developed which makes use of direct imaging of the individual beams using beam-gas and beam-beam interactions. This beam imaging method is made possible by the high resolution of the LHCb vertex detector and the close proximity of the detector to the beams, and allows beam parameters such as positions, angles and widths to be determined. The results of the two methods have comparable precision and are in good agreement. Combining the two methods, an overall precision of 3.5% in the absolute luminosity determination is reached. The techniques used to transport the absolute luminosity calibration to the full 2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6, 9 and 10 and corresponding explanation in the tex