Development and validation of an intrinsic dissolution method for nimodipine polymorphs

The polymorphs of nimodipine, Modification I (Mod I), the metastable racemate, and Modification II (Mod II), the stable conglomerate, were evaluated by means of the intrinsic dissolution procedure. For this purpose, a hydro alcoholic solution (ethanol:water, 50:50, v/v) was selected as the dissolution medium, maintained at 37±0.5°C. Different rotation speeds were tested (50, 75 and 100 rpm) and the lower one was chosen for the test validation. Although the sample initially characterized as polymorph Mod I presented higher intrinsic dissolution rates in all the conditions tested, no statistical differences were noticed between the two polymorphs. This result can be attributed to the partial solution-mediated phase transformation from Mod I to Mod II, detected through X-ray powder diffraction and differential scanning calorimetry. Also, reliable intrinsic dissolution rate data were acquired for the polymorph Mod II. The dissolution method was validated, being considered stable, specific, linear, sensible, accurate and precise.      

Cocrystal Formation through Mechanochemistry: from Neat and Liquid‐Assisted Grinding to Polymer‐Assisted Grinding

Mechanochemistry is an effective method for the preparation of multicomponent crystal systems. In the present work, we propose an alternative to the established liquid‐assisted grinding (LAG) approach. Polymer‐assisted grinding (POLAG) is demonstrated to provide a new class of catalysts for improving reaction rate and increasing product diversity during mechanochemical cocrystallization reactions. We demonstrate that POLAG provides advantages comparable to the conventional liquid‐assisted process, whilst eliminating the risk of unwanted solvate formation as well as enabling control of resulting particle size. It represents a new approach for the development of functional materials through mechanochemistry, and possibly opens new routes toward the understanding of the mechanisms and pathways of mechanochemical cocrystal formation.     

High-Temperature Quantum Tunneling and Hydrogen Bonding Rearrangements Characterize the Solid-Solid Phase Transitions in a Phosphonium-Based Protic Ionic Liquid

We report the complex phase behavior of the glass forming protic ionic liquid (PIL) d3-octylphosphonium bis(trifluoromethylsulfonyl)imide [C₈H₁₇PD₃][NTf₂] by means of solid-state NMR spectroscopy. Combined line shape and spin relaxation studies of the deuterons in the PD₃ group of the octylphosphonium cation allow to map and correlate the phase behavior for a broad temperature range from 71 K to 343 K. In the solid PIL at 71 K, we observed a static state, characterized by the first deuteron quadrupole coupling constant reported for PD₃ deuterons. A transition enthalpy of about 12 kJ mol⁻¹ from the static to the mobile state with increasing temperature suggests the breaking of a weak, charge-enhanced hydrogen bond between cation and anion. The highly mobile phase above 100 K exhibits an almost disappearing activation barrier, strongly indicating quantum tunneling. Thus, we provide first evidence of tunneling driven mobility of the hydrogen bonded P−D moieties in the glassy state of PILs, already at surprisingly high temperatures up to 200 K. Above 250 K, the mobile phase turns from anisotropic to isotropic motion, and indicates strong internal rotation of the PD₃ group. The analyzed line shapes and spin relaxation times allow us to link the structural and dynamical behavior at molecular level with the phase behavior beyond the DSC traces.     

Shape resonances in slow electron scattering by aromatic molecules. I. Anthraquinone derivatives

A series of anthraquinone (C(14)O(2)H(8)) derivatives has been studied by means of electron capture negative ion mass spectrometry (ECNI-MS), photoelectron spectroscopy (PES), and AM1 quantum chemical calculations. Mean lifetimes of molecular negative ions M(-.) (MNI) have been measured. The mechanism of long-lived MNI formation in the epithermal energy region of incident electrons has been investigated. A simple model of a molecule (a spherical potential well with the repulsive centrifugal term) has been applied for the analysis of the energy dependence of cross sections at the first stage of the electron capture process. It has been shown that a temporary resonance of MNI at the energy approximately 0.5 eV corresponds to a shape resonance with lifetime 1-2.10(-13) s in the f-partial wave (l = 3) of the incident electron. The next resonant state of MNI at the energy approximately 1.7 eV has been associated with the electron excited Feshbach resonance (whose parent state is a triplet npi* transition). In all cases the initial electron state of the MNI relaxes into the ground state by means of a radiationless transition, and the final state of the MNI is a nuclear excited resonance with a lifetime measurable on the mass spectrometry timescale. Copyright 1999 John Wiley & Sons, Ltd.     

A finite element formulation for global linear stability analysis of a nominally two‐dimensional base flow

A stabilized finite element method, to carry out the linear stability analysis of a two‐dimensional base flow to three‐dimensional perturbations that are periodic along span, is presented. The resulting equations for the time evolution of the disturbance requires a solution to the generalized eigenvalue problem. The analysis is global in nature and is also applicable to non‐parallel flows. Equal‐order‐interpolation functions for velocity and pressure are utilized. Stabilization terms are added to the Galerkin formulation to admit the use of equal‐order‐interpolation functions and to eliminate node‐to‐node oscillations that might arise in advection‐dominated flows. The proposed formulation is tested on two flow problems. First, the mode transitions in the circular Couette flow are investigated. Two scenarios are considered. In the first one, the outer cylinder is at rest, while the inner one spins. Two linearly unstable modes are identified. The primary mode is real and represents the axisymmetric Taylor vortices. The second mode is complex and consists of spiral vortices. For the counter‐rotating cylinders, the primary transition is via the appearance of spiral vortices. Excellent agreement with results from earlier studies is observed. The formulation is also utilized to investigate the parallel and oblique modes of vortex shedding past a cylinder for the Re = 100 flow. It is found that the flow is associated with a large number of unstable oblique shedding modes. The parallel mode of vortex shedding is a special case of this family of modes and is associated with the largest growth rate. Copyright © 2014 John Wiley & Sons, Ltd.     

Interpolating Strange Attractors via Fractional Brownian Bridges

We present a novel method for interpolating univariate time series data. The proposed method combines multi-point fractional Brownian bridges, a genetic algorithm, and Takens’ theorem for reconstructing a phase space from univariate time series data. The basic idea is to first generate a population of different stochastically-interpolated time series data, and secondly, to use a genetic algorithm to find the pieces in the population which generate the smoothest reconstructed phase space trajectory. A smooth trajectory curve is hereby found to have a low variance of second derivatives along the curve. For simplicity, we refer to the developed method as PhaSpaSto-interpolation, which is an abbreviation for phase-space-trajectory-smoothing stochastic interpolation. The proposed approach is tested and validated with a univariate time series of the Lorenz system, five non-model data sets and compared to a cubic spline interpolation and a linear interpolation. We find that the criterion for smoothness guarantees low errors on known model and non-model data. Finally, we interpolate the discussed non-model data sets, and show the corresponding improved phase space portraits. The proposed method is useful for interpolating low-sampled time series data sets for, e.g., machine learning, regression analysis, or time series prediction approaches. Further, the results suggest that the variance of second derivatives along a given phase space trajectory is a valuable tool for phase space analysis of non-model time series data, and we expect it to be useful for future research.     

Novel Phosphonium-Based Ionic Liquid Electrolytes for Battery Applications

In this study, we address the fundamental question of the physicochemical and electrochemical properties of phosphonium-based ionic liquids containing the counter-ions bis(trifluoromethanesulfonyl)imide ([TFSI]⁻) and bis(fluorosulfonyl)imide ([FSI]⁻). To clarify these structure–property as well as structure–activity relationships, trimethyl-based alkyl- and ether-containing phosphonium ILs were systematically synthesized, and their properties, namely density, flow characteristics, alkali metal compatibility, oxidative stability, aluminum corrosivity as well as their use in Li-ion cells were examined comprehensively. The variable moiety on the phosphonium cation exhibited a chain length of four and five, respectively. The properties were discussed as a function of the side chain, counter-ion and salt addition ([Li][TFSI] or [Li][FSI]). High stability coupled with good flow characteristics were found for the phosphonium IL [P1114][TFSI] and the mixture [P1114][TFSI] + [Li][TFSI], respectively.     

Untersuchung von Wasser

Ohne Zusammenfassung     

High-performance column liquid chromatographic method for the simultaneous determination of buclizine, tryptophan, pyridoxine, and cyanocobalamin in tablets and oral suspension

An HPLC method was developed and validated for the simultaneous determination of buclizine, tryptophan, pyridoxine, and cyanocobalamin in pharmaceutical formulations. The chromatographic separation was carried out on an RP-C18 column using a mobile phase gradient of methanol, 0.015 M phosphate buffer (pH 3.0), and 0.03 M phosphoric acid at a flow rate of 1.0 mL/min and UV detection at 230, 280, and 360 nm, respectively, for buclizine, tryptophan, pyridoxine, and cyanocobalamin. The method validation yielded good results with respect to linearity (r>0.999), specificity, precision, accuracy, and robustness. The RSD values for intraday and interday precision were below 1.82 and 0.63%, respectively, and recoveries ranged from 98.11 to 101.95%. The method was successfully applied for the QC analysis of buclizine, tryptophan, pyridoxine, and cyanocobalamin in tablets and oral suspension.