A novel approach to crystallisation of nanodispersible microparticles by spray drying for improved tabletability

YesHigh-dose API powders which are to be tableted by direct compression should have high compactibility and compressibility. This note reports on a novel approach to the manufacture of crystalline powders intended for direct compaction with improved compactibility and compressibility properties. The poorly compactable API, chlorothiazide, was spray dried from a water/acetone solvent mix producing additive-free nanocrystalline microparticles (NCMPs) of median particle size 3.5 μm. Tablets compacted from NCMPs had tensile strengths ranging from 0.5 to 4.6 MPa (compared to 0.6–0.9 MPa for tablets of micronised CTZ) at compression forces ranging from 6 kN to 13 kN. NCMP tablets also had high porosities (34–20%) and large specific surface areas (4.4–4.8 m2/g). The time taken for tablets made of NCMPs to erode was not statistically longer (p > 0.05) than for tablets made of micronised CTZ. Fragmentation of NCMPs on compression was observed. The volume fraction of particles below 1 μm present in the suspension recovered after erosion of NCMP tablets was 34.8 ± 3.43%, while no nanosized particles were detected in the slurry after erosion of compacted micronised CTZ.Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number 07/SRC/B1158

Fast relaxation in a fragile liquid under pressure

The incoherent dynamic structure factor of ortho-terphenyl has been measured by neutron time-of-flight and backscattering technique in the pressure range from 0.1 MPa to 240 MPa for temperatures between 301 K and 335 K. Tagged-particle correlations in the compressed liquid decay in two steps. The alpha-relaxation lineshape is independent of pressure, and the relaxation time proportional to viscosity. A kink in the amplitude f_Q(P) reveals the onset of beta relaxation. The beta-relaxation regime can be described by the mode-coupling scaling function; amplitudes and time scales allow a consistent determination of the critical pressure P_c(T). alpha and beta relaxation depend in the same way on the thermodynamic state; close to the mode-coupling cross-over, this dependence can be parametrised by an effective coupling Gamma ~ n*T**{-1/4}.Comment: 4 Pages of RevTeX, 4 figures (submitted to Physical Review Letters

A Comparison of Preservation Methods of Roughages from Grassland in Poland

The objective of this study was to determine whether the preservation method has an influence on the nutritive value of roughages obtained from grasslands. The silage made in clamps and in big cylindrical bales were compared. During chemical studies, dry matter, crude protein, crude fiber, crude ash, nitrogen free extracts and fat level were determined. The digestible energy of each feed was calculated. The content of particular acids (lactic, acetic and butyric) in the mass of silage was determined. The silages were tested by feeding to ruminants. The obtained results show that the quality of both silages was good. The difference in the nutritive value between the two silages was not significant

Corresponding States of Structural Glass Formers

The variation with respect to temperature T of transport properties of 58 fragile structural glass forming liquids (68 data sets in total) are analyzed and shown to exhibit a remarkable degree of universality. In particular, super-Arrhenius behaviors of all super-cooled liquids appear to collapse to one parabola for which there is no singular behavior at any finite temperature. This behavior is bounded by an onset temperature To above which liquid transport has a much weaker temperature dependence. A similar collapse is also demonstrated, over the smaller available range, for existing numerical simulation data.Comment: 6 pages, 2 figures. Updated References, Table Values, Submitted for Publicatio

Formation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic acid

YesMulti-ionizable compounds, such as dicarboxylic acids, offer the possibility of forming salts of drugs with multiple stoichiometries. Attempts to crystallize ciprofloxacin, a poorly water-soluble, amphoteric molecule with succinic acid (S) resulted in isolation of ciprofloxacin hemisuccinate (1:1) trihydrate (CHS-I) and ciprofloxacin succinate (2:1) tetrahydrate (CS-I). Anhydrous ciprofloxacin hemisuccinate (CHS-II) and anhydrous ciprofloxacin succinate (CS-II) were also obtained. It was also possible to obtain stoichiometrically equivalent amorphous salt forms, CHS-III and CS-III, by spray drying and milling, respectively, of the drug and acid. Anhydrous CHS and CS had melting points at ∼215 and ∼228 °C, while the glass transition temperatures of CHS-III and CS-III were ∼101 and ∼79 °C, respectively. Dynamic solubility studies revealed the metastable nature of CS-I in aqueous media, resulting in a transformation of CS-I to a mix of CHS-I and ciprofloxacin 1:3.7 hydrate, consistent with the phase diagram. CS-III was observed to dissolve noncongruently leading to high and sustainable drug solution concentrations in water at 25 and 37 °C, with the ciprofloxacin concentration of 58.8 ± 1.18 mg/mL after 1 h of the experiment at 37 °C. This work shows that crystalline salts with multiple stoichiometries and amorphous salts have diverse pharmaceutically relevant properties, including molecular, solid state, and solubility characteristics.Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number 07/SRC/ B1158

Three-dimensional geometry controls division symmetry in stem cell colonies

Proper control of division orientation and symmetry, largely determined by spindle positioning, is essential to development and homeostasis. Spindle positioning has been extensively studied in cells dividing in two-dimensional (2D) environments and in epithelial tissues, where proteins such as NuMA (also known as NUMA1) orient division along the interphase long axis of the cell. However, little is known about how cells control spindle positioning in three-dimensional (3D) environments, such as early mammalian embryos and a variety of adult tissues. Here, we use mouse embryonic stem cells (ESCs), which grow in 3D colonies, as a model to investigate division in 3D. We observe that, at the periphery of 3D colonies, ESCs display high spindle mobility and divide asymmetrically. Our data suggest that enhanced spindle movements are due to unequal distribution of the cell–cell junction protein E-cadherin between future daughter cells. Interestingly, when cells progress towards differentiation, division becomes more symmetric, with more elongated shapes in metaphase and enhanced cortical NuMA recruitment in anaphase. Altogether, this study suggests that in 3D contexts, the geometry of the cell and its contacts with neighbors control division orientation and symmetry

Chloride catalytic determination as potential tool to assess metal Ion bioavailability in water

This paper focuses on the development of an environmentally friendly sequential injection (SI) method for the determination of chloride in water samples from dynamic water systems. Chloride quantification is highly relevant, as it may affect metal ion bioavailability and potential toxicity to the environment. The approach was established based on the catalytic reaction of chloride ions in the colorimetric reaction between 3,3′,5,5′-tetramethylbenzidine (TMB) and hydrogen peroxide. Optimisation studies were performed regarding several parameters such as reaction pH, reagent volume and concentration, reaction time, and flow rates. As such, it was possible to obtain a wide dynamic range of 60 to 1000 mM, with a limit of detection and quantification of 17 and 58 mM, respectively, and a relative standard deviation of 7%. Validation was performed by analysing 13 water samples from dynamic water systems, namely seawater, estuarine water, and estuarine harbour water, with the SI method developed and by comparing the results obtained to potentiometric titration as the reference method. The relative error of these comparisons was not significant (<10%). Interference studies were also performed and showed no significant effect on the performance of the system (interference percentage < 10%), proving that a robust and sensitive system was developed

Three-dimensional geometry controls division symmetry in stem cell colonies.

Proper control of division orientation and symmetry, largely determined by spindle positioning, is essential to development and homeostasis. Spindle positioning has been extensively studied in cells dividing in two-dimensional (2D) environments and in epithelial tissues, where proteins such as NuMA (also known as NUMA1) orient division along the interphase long axis of the cell. However, little is known about how cells control spindle positioning in three-dimensional (3D) environments, such as early mammalian embryos and a variety of adult tissues. Here, we use mouse embryonic stem cells (ESCs), which grow in 3D colonies, as a model to investigate division in 3D. We observe that, at the periphery of 3D colonies, ESCs display high spindle mobility and divide asymmetrically. Our data suggest that enhanced spindle movements are due to unequal distribution of the cell-cell junction protein E-cadherin between future daughter cells. Interestingly, when cells progress towards differentiation, division becomes more symmetric, with more elongated shapes in metaphase and enhanced cortical NuMA recruitment in anaphase. Altogether, this study suggests that in 3D contexts, the geometry of the cell and its contacts with neighbors control division orientation and symmetry. This article has an associated First Person interview with the first author of the paper

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Post-imperialism, postcolonialism and beyond: towards a periodisation of cultural discourse about colonial legacies

Taking German history and culture as a starting point, this essay suggests a historical approach to reconceptualising different forms of literary engagement with colonial discourse, colonial legacies and (post-) colonial memory in the context of Comparative Postcolonial Studies. The deliberate blending of a historical, a conceptual and a political understanding of the ‘postcolonial’ in postcolonial scholarship raises problems of periodisation and historical terminology when, for example, anti-colonial discourse from the colonial period or colonialist discourse in Weimar Germany are labelled ‘postcolonial’. The colonial revisionism of Germany’s interwar period is more usefully classed as post-imperial, as are particular strands of retrospective engagement with colonial history and legacy in British, French and other European literatures and cultures after 1945. At the same time, some recent developments in Francophone, Anglophone and German literature, e.g. Afropolitan writing, move beyond defining features of postcolonial discourse and raise the question of the post-postcolonial