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.     

Concept-Driven Interaction Design Research

In this article, we explore a concept-driven approach to interaction design research with a specific focus on theoretical advancements. We introduce this approach as a complementary approach to more traditional, and well-known, user-centered interaction design approaches. A concept-driven approach aims at manifesting theoretical concepts in concrete designs. A good concept design is both conceptually and historically grounded, bearing signs of the intended theoretical considerations. In the area of human–computer interaction and interaction design research, this approach has been quite popular but not necessarily explicitly recognized and developed as a proper research methodology. In this article, we demonstrate how a concept-driven approach can coexist, and be integrated with, common user-centered approaches to interaction design through the development of a model that makes explicit the existing cycle of prototyping, theory development, and user studies. We also present a set of basic principles that could constitute a foundation for concept driven interaction research, and we have considered and described the methodological implications given these principles. For the field of interaction design research we find this as an important point of departure for taking the next step toward the construction and verification of theoretical constructs that can help inform and guide future design research projects on novel interaction technologies.     

A Danish case: portfolio evaluation and its impact on energy efficiency policy

A political agreement from 2005 stated that an evaluation of the entire Danish energy efficiency policy portfolio must be carried out before the end of 2008, with the aim to assess the following: (1) Is the policy portfolio sufficient to meet the energy efficiency targets? (2) Do the policies enable the national goals to be met in a cost-effective manner? (3) Is the overall design of the policy portfolio appropriate? The evaluation gave recommendations on how to improve and develop the portfolio, mainly using cost-effectiveness as criteria. The evaluation was completed in December 2008, and this paper presents the main findings and the subsequent impact on Danish policy. A key lesson learned is the importance of including all energy efficiency policies in the evaluation. Examining the entire portfolio of policies (as opposed to only selected policies) gave way to findings that would otherwise not have been captured. With its broad perspective, the evaluation found that the policy instruments prioritised the commercial and industrial sectors less than the household and public sectors. The recommendations made by the authors contributed to the implementation of new taxes for the commercial and industrial sectors together with the reform of the Electricity Saving Trust to a Centre for Energy Savings charged with energy savings within all sectors, except transport—both which have been important steps towards a more cost-effective solution.     

Polylactide latex/nanofibrillated cellulose bionanocomposites of high nanofibrillated cellulose content and nanopaper network structure prepared by a papermaking route

Previous attempts to use polylactide (PLA) latex particles and nanofibrillated cellulose (NFC) in papermaking processing have been limited to low NFC content. In the present study, a bionanocomposite material was successfully produced using a PLA latex and NFC. The components were mixed using a wet mixing method and bionanocomposite films were made by filtration followed by hot pressing. In composite materials, the dispersion of the reinforcing component in the matrix is critical for the material properties. Biopolymers such as PLA are non-polar and soluble only in organic solvents; NFC is, however, highly hydrophilic. By utilizing latex, i.e., an aqueous dispersion of biopolymer micro-particles, wet mixing is possible and the problem of aggregation of the hydrophilic nanocellulose in organic solvent is avoided. The properties of the resulting NFC/PLA latex bionanocomposite films were analyzed. Thorough blending resulted in good dispersion of the reinforcing component within the matrix. Adding increasing amounts of NFC improved the Young's modulus, tensile strength, and strain at break of the bionanocomposite material. The increase in the tensile properties was linear with increasing NFC content as a result of the good dispersion. The NFC also improved the thermal stability of the bionanocomposite material. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Strips of hourly power options—Approximate hedging using average-based forward contracts

We study approximate hedging strategies for a contingent claim consisting of a strip of independent hourly power options. The payoff of the contingent claim is a sum of the contributing hourly payoffs. As there is no forward market for specific hours, the fundamental problem is to find a reasonable hedge using exchange-traded forward contracts, e.g. average-based monthly contracts. The main result is a simple dynamic hedging strategy that reduces a significant part of the variance. The idea is to decompose the contingent claim into mathematically tractable components and to use empirical estimations to derive hedging deltas. Two benefits of the method are that the technique easily extends to more complex power derivatives and that only a few parameters need to be estimated. The hedging strategy based on the decomposition technique is compared with dynamic delta hedging strategies based on local minimum variance hedging, using a correlated traded asset.     

Enhancing the electrical conductivity of carbon black/graphite nanoplatelets: Poly(ethylene‐butyl acrylate) composites by melt extrusion

The influence of processing parameters such as screw geometry, temperature profile, and screw speed on the electrical properties of hybrid composites consisting of graphite nanoplatelets and carbon black in ethyl butyl acrylate was studied. Two different screws were used to compound the hybrid composites at two different temperatures and two different screw speeds. A beneficial effect was noted with regard to the electrical properties when adding nanoplatelets to the filler system. The cause could be a synergistic effect due to the difference in particle shape of the two fillers. Lower percolation thresholds were obtained with the conventional screw due to less breakage of the graphite nanoplatelets compared to the barrier screw. No significant changes of the electrical properties were observed when changing the temperature profiles or the screw speeds. Furthermore, the melt viscosity of the compounds was not appreciably affected at the rather low filler contents used here. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42897.     

Epoxy–graphite oxide nanocomposites: Mechanical properties

Graphite oxide (GO) produced by Hummers method was added to epoxy for strengthening purpose. Generally the E‐modulus was increased due to the GO addition; however, depending on the treatment of the GO an increase or decrease was observed for the glass transition temperature. The change in glass transition was a result of changes in the curing behavior. Addition of GO initially increased the curing speed; however, the final curing degree was lower and was dependent on the type of GO added. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43591.     

The Effects of KCl,NaCl and K<Subscript>2</Subscript>CO<Subscript>3</Subscript> on the High-Temperature Oxidation Onset of Sanicro 28 Steel

The present study investigates the early stages in the oxidation process of Sanicro 28 (Fe31Cr27Ni) stainless steel when exposed to an alkali salt (KCl, NaCl or K₂CO₃) for 2 h at 450 and 535 °C. After the exposure, the oxidized samples were analyzed with a combinatory method (CA, XPS and SEM–EDX). It was found that all three salts were corrosive, and the overall oxidation reaction rate was much higher at 535 °C than at 450 °C. There were clear differences in terms of the impact of cations (Na⁺, K⁺) and anions (Cl^?, CO₃ ^2?) on the initial corrosion process at both temperatures. When focusing on the cations, the presence of potassium ions resulted in a higher rate of chromate formation than in the presence of sodium ions. When studying the effect of anions, the oxidation of iron and chromium occurred at higher rates in the presence of both chloride salts than in the presence of the carbonate salt, and chloride salts seemed to possess higher diffusion rate in the gas phase and along the surface than carbonate salts. Moreover, at the higher temperature of 535 °C, the formed chromate reacted further to chromium oxide, and an ongoing oxidation process of iron and chromium was identified with a significantly higher reaction rate than at 450 °C.     

Simulation of the interactions between hydraulic and natural fractures using a fracture mechanics approach

HYDROCK method aims to store thermal energy in the rock mass using hydraulically propagated fracture planes. The hydraulic fractures can interact with the pre-existing natural fractures resulting in a complex fracture network, which can influence the storage performance. This study investigates the interactions between hydraulic and natural fractures using a fracture mechanics approach. The new functionality of the fracture mechanics modelling code FRACOD that enables crossing of hydraulically driven fracture by a pre-existing fracture is presented. A series of two-dimensional numerical models is prepared to simulate the interaction at different approach angles in granitic rock of low permeability. It is demonstrated that multiple interaction mechanisms can be simulated using the fracture mechanics approach. The numerical results are in agreement with the modified Renshaw and Pollard analytical criterion for fracture crossing. The results show that for large approach angles, the hydraulic fracture crosses the natural fracture, whereas for small approach angles, the hydraulic fracture activates the natural fracture and the wing-shaped tensile fractures are propagated from its tips. Thus, the presence of fractures with low dip angles can lead to the growth of more complex fracture network that could impair the thermal performance of the HYDROCK method.     

Flue gas cleaning by periodic absorption

Simulations and designs are presented of conventional and periodic SO₂ absorption from exhaust gases using salt water as absorption solvent. Operating conditions resemble those of a maritime operation, involving relatively small amounts of SO₂, so the separation is in the linear region. The advantages of periodic operation, as already demonstrated for conventional distillation remain valid for absorption processes: Less tall towers, than staged towers are possible, or substantially less salt water is required for the process employing periodic cycling.