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

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

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

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

Galaxie

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

Evidence for PopIII-like Stellar Populations in the Most Luminous Lyman-α Emitters at the Epoch of Reionization: Spectroscopic Confirmation

Galaxie

The trophectoderm acts as a niche for the inner cell mass through C/EBPα-regulated IL-6 signaling

IL-6 has been shown to be required for somatic cell reprogramming into induced pluripotent stem cells (iPSCs). However, how Il6 expression is regulated and whether it plays a role during embryo development remains unknown. Here, we describe that IL-6 is necessary for C/EBPα-enhanced reprogramming of B cells into iPSCs but not for B cell to macrophage transdifferentiation. C/EBPα overexpression activates both Il6 and Il6ra genes in B cells and in PSCs. In embryo development, Cebpa is enriched in the trophectoderm of blastocysts together with Il6, while Il6ra is mostly expressed in the inner cell mass (ICM). In addition, Il6 expression in blastocysts requires Cebpa. Blastocysts secrete IL-6 and neutralization of the cytokine delays the morula to blastocyst transition. The observed requirement of C/EBPα-regulated IL-6 signaling for pluripotency during somatic cell reprogramming thus recapitulates a physiologic mechanism in which the trophectoderm acts as niche for the ICM through the secretion of IL-6.Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved

The rise and fall of star formation in z ~ 0.2 merging galaxy clusters

Galaxie