Physical Characterization of Anhydrous and Hydrous Forms of the Hydrochloride Salt of BVT.5182 A Novel 5-HT6 Receptor Antagonist

ABSTRACT

The physicochemical properties of 1-benzenesulfonyl-4-(piperazin-1-yl)-indole hydrochloride, a novel 5-HT₆ receptor antagonist for the treatment of obesity were characterized. Two solid state forms were identified at ambient conditions (23°C): an anhydrate form (1) and a hydrate form (2), with 1.5 moles of H₂O. The latter easily dehydrates and rehydrates without affecting the crystal morphology. Investigations of the propensity for interconversion between the two forms reveal that a) conversion of 2→1 takes place above 145°C and that b) conversion of 1→2 only occurs after crystallization from supersaturated aqueous solutions at a water activity ≥0.94 or in the presence of comparable amounts of crystals of 2 in water at ambient conditions. However, in an equimolar suspension of 1 and 2 at 37°C no phase transformation was observed. Thus, the difference in chemical potential between the two forms is small. Form 1 was shown to have overall favorable solid state properties and, hence, considered the preferred form for continued pharmaceutical development. The characterization was performed by means of light microscopy, scanning electron microscopy, powder X-ray diffraction, FTIR/NIR-spectroscopy, differential scanning calorimetry, hot stage microscopy, thermogravimetry, dynamic vapor sorption, Karl Fischer water content determination, phase stability studies of suspensions, solubility, and intrinsic dissolution rate measurements.     

Microstructural Investigation of the HCl-Induced Corrosion of the Austenitic Alloy 310S (52Fe26Cr19Ni) at 500 °C

This paper investigates the influence of 500 ppm HCl in a 5 %O₂–95 %N₂ atmosphere on the oxidation of the austenitic stainless steel AISI 310S at 500 °C. Laboratory exposures were made for one, 24, 72 and 168 h and the samples were analysed with XRD, SEM/EDX, FIB and TEM/EDX. When exposed in oxygen a thin and protective chromium-rich oxide scale forms. Addition of HCl causes significantly accelerated corrosion. Within the first hour of exposure, accumulations of FeCl₂, CrCl₂ and NiCl₂ forms below the chromium-rich oxide, especially at steel grain boundaries. The chlorine-induced corrosion is suggested to occur through an electrochemical reaction, in which the dissociation of HCl to form chloride ions at the scale surface is coupled to the oxidation of the metal surface beneath the scale by an outwards electronic current and inwards diffusion of chloride ions along oxide grain boundaries.     

Study of Lewis acid catalyzed chemical bromination and bromoalkylation of multi-walled carbon nanotubes

Chemical functionalization of carbon nanotubes (CNT) with nucleophiles requires introduction of electrophilic reactive sites on the CNTs. This can, for instance, be accomplished by the chemical bromination procedure with elemental bromine and a set of Lewis acids (BBr₃, BF₃ × Et₂O, AlBr₃, FeBr₃, ZnBr₂, TiBr₄, SiBr₄, SnBr₄, VBr₃) or a radical starter like dibenzoylperoxide (DBPO) in appropriate solvents at varied temperature. The present approach to electrophilic sites relies on the well-known electrophilic aromatic substitution or addition of bromine with aromatic structural units. In addition to the use of bromine, the introduction of haloalkyl groups was also investigated here using bis-electrophiles or haloalcohols and Brønsted acids. The advantages and drawbacks of the studied reaction conditions, the obtained degree of bromination as analyzed by X-ray photoelectron spectroscopy (XPS) and the amount of introduced bromine that can be substituted by a nucleophile are presented and discussed.     

GMOfinder—A GMO Screening Database

The development and cultivation of genetically modified crops is still increasing globally. Food and feed imports from outside the European Union (EU) will subsequently require more effort from the responsible authorities in monitoring the compliance with effective labelling regulations. The aim of this study was the development of the GMOfinder, a database for collection and interpretation of information related to the screening for genetically modified organisms (GMOs). Different genetic elements (e.g. promoters, terminators, structural genes) are artificially introduced into plants to establish new genetic modifications. The introduced elements may vary between GMO events, depending on the intended trait(s). Screening for such inserted elements with (real-time) polymerase chain reaction is a common first step to analyse samples for the presence of any genetical modification. From the pattern of detectable and nondetectable elements, valuable conclusions about the identity of putative present GMO event(s) can be drawn with the GMOfinder. Information about selected genetic elements from the literature, applications for authorisation and other (web) sources were systematically integrated in a tabular matrix format. Special care was taken to additionally record the sources of the information, thus facilitating evaluation of screening results, and tracing of possible errors in the matrix. The GMOfinder accesses data from the element matrix with implemented algorithms and facilitates to interpret the outcome of screenings. Such a preselection helps to systematically narrow down the candidates for subsequent identification reactions. Optional display of events with potentially masked elements completes the included features.     

Time-synchronised hardware-in-the-loop simulation — Applied to sheet-metal press line optimisation

This paper presents an off-line process parameter tuning method, focussing on complex control functions for automated manufacturing systems. The proposed method is based on a combination of simulation-based optimisation and time-synchronised hardware-in-the-loop simulation. Real industrial control systems, e.g., PLCs, are included in the simulation, executing the unchanged control code from the manufacturing plant. This approach allows all plant control functions to be included, even time-critical feedback loops and vendor secret blocks such as motion control. Consequently, the method suggested manages the problems identified in previously presented simulation-based approaches. Furthermore, a case study of an automotive sheet-metal press line has been performed to verify the proposed method, with successful results.     

Through Process Modelling of Surface Densified PM Gears

Through process modelling of surface densified gears produced by powder metallurgy (PM) was established by coupling the modelling of the manufacturing processes surface densification, carburization, and heat treatment. The complete model allows the prediction of the local microstructure and hardness in the gear as well as the appearance and direction of residual stresses in the final part. The structural integrity of the part is governed, on the one hand, by the local material properties and residual stresses and, on the other hand, by the load stresses calculated for typical operating conditions. A simplified hardness dependent Haigh diagram was used to calculate the maximum allowable cyclic stresses for the gear tooth and to derive a local utilization ratio as target entity for optimization of the individual steps of the production chain.