High pressure treatment of pharmaceutical drug delivery and related systems

Abstract

Solids like layer silicates (kaolinite and montmorillonite) as well as ZnO are in use in pharmacy. They are pressure treated and subsequently analyzed by means of ESR spectroscopy. The structural changes indicated by Fe³⁺ ions and paramagnetic defects are reponsible for the enhanced chemical activity of the pressurized systems.

Especially active Fe-O-species are formed which can react with intercacalated organic molecules. The most probable first step of such reactions will be a solid state single electron transfer. Spin probes and spin traps were used to prove this statements. The activation of the drug delivery systems by mechanical treatments is of importance for the stability of the drugs incorporated.     

Generation of nanoparticles by spark discharge

The production of nanoparticles by microsecond spark discharge evaporation in inert gas is studied systematically applying transmission electron microscopy, mobility analysis and BET surface area measurement. The method of spark discharge is of special interest, because it is continuous, clean, extremely flexible with respect to material, and scale-up is possible. The particle size distributions are narrow and the mean primary particle size can be controlled via the energy per spark. Separated, unagglomerated particles, 3–12 nm in size, or agglomerates can be obtained depending on the flow rate. The nanoparticulate mass produced is typically 5 g/kWh. A formula is given, which estimates the mass production rate via thermal conductivity, evaporation enthalpy and the boiling point of the material used. We showed that with gas purified at the spot, the method produced gold particles that were so clean that sintering of agglomerated particles occurred at room temperature. The influence of a number of parameters on the primary particle size and mass production rate was studied and qualitatively understood with a model of Lehtinen and Zachariah (J Aerosol Sci 33:357–368, 2002). Surprisingly high charging probabilities for one polarity were obtained. Spark generation is therefore of special interest for producing monodisperse aerosols or particles of uniform size via electrical mobility analysis. Qualitative observations in the present study include the phenomenon of material exchange between the electrodes by the spark, which opens the possibility of producing arbitrary mixtures of materials on a nanoscale. If spark generation of nanoparticles is performed in a standing or almost standing gas, an aerogel of a web-like structure forms between surfaces of different electrical potential.     

Imaging delocalized electron clouds: photoionization of C(60) in Fourier reciprocal space

The dynamics of the photoionization of the two outermost orbitals of C(60) has been studied in the oscillatory regime from threshold to the carbon K edge. We show that geometrical properties of the fullerene electronic hull, such as its diameter and thickness, are contained in the partial photoionization cross sections by examining ratios of partial cross sections as a function of the photon wave number in the Fourier conjugated space. Evaluated in this unconventional manner photoemission data reveal directly the desired spatial information.     

Probabilistic approach to homogenization of viscosity solutions of parabolic PDEs

In this paper, we develop the probabilistic approach to homogenization problems of viscosity solutions of systems of semilinear parabolic PDEs. Our main tool is the nonlinear Feynman-Kac formula. Received July 1998     

Passivity and Microlocal Spectrum Condition

In the setting of vector-valued quantum fields obeying a linear wave-equation in a globally hyperbolic, stationary spacetime, it is shown that the two-point functions of passive quantum states (mixtures of ground- or KMS-states) fulfill the microlocal spectrum condition (which in the case of the canonically quantized scalar field is equivalent to saying that the two-pnt function is of Hadamard form). The fields can be of bosonic or fermionic character. We also give an abstract version of this result by showing that passive states of a topological *-dynamical system have an asymptotic pair correlation spectrum of a specific type. Received: 9 February 2000 / Accepted: 7 June 2000     

Simulation based analysis of secondary effects on solder fatigue

Secondary effects on thermal fatigue of solder joints, which frequently have been neglected, were studied by means of the finite element method (FEM). Based on a semi-empirical approach to predict fatigue life by evaluating the cyclic accumulated equivalent creep strain or energy density, effects of organic boards intrinsic properties on solder joint fatigue were investigated. Aspects of more realistic FR-4 board modelling were studied, in particular concerning its in-plane anisotropy and intrinsic warpage behaviour. Intrinsic board warpage was measured on test board level as well as for boards from series production. High intrinsic warpage was in particular found for several test boards. The effects for the worst case scenario observed so far were analysed for both first level and second level interconnects. The change in predicted fatigue life varied between 30% and 500%, the latter most critical effects were found at large QFN components. Another secondary effect studied was to include the frequently neglected interfacial intermetallics into FEM. It turned out that for components with relatively large standoff like LFBGAs the effects were actually negligible, but for the highly miniaturized components like chip resistors CR0201 they are the decisive factor.     

Quantum Field Theory on a Discrete Space and Noncommutative Geometry

We analyze in detail the quantization of a simple noncommutative model of spontaneous symmetry breaking in zero dimensions taking into account the noncommutative setting seriously. The connection to the counting argument of Feynman diagrams of the corresponding theory in four dimensions is worked out explicitly. Special emphasis is put on the motivation as well as the presentation of some well-known basic notions of quantum field theory which in the zero-dimensional theory can be studied without being spoiled by technical complications due to the absence of divergencies.     

Application of centrifugal vacuum concentrators in residue analysis

Summary Centrifugal vacuum concentrators can be applied in residue analysis successfully: They prevent the samples from bumping and foaming. Even methanol/water- or acetonitrile/water-mixtures as extracts from food or other samples can be concentrated without separation of water prior to the evaporation process. Sulfonamides and other drugs can be concentrated with 100% recovery. Extracts with some light-sensitive substances (nitrofuranes) were evaporated without losses, as well as some hydrolysis-sensitive substances (penicillins) solved in water, whereas tetracyclines decompose in aqueous solution considerably. For more volatile substances (such as organochlorine pesticides or polychlorinated biphenyls) centrifugal vacuum concentrators can be used for preconcentration e.g. of the gelchromatographic eluate. Further, centrifugal vacuum concentrators can automate the evaporation process. In comparison to rotary evaporators, they save time for the laboratory staff when running series of 4 or more samples. It is very important to supply permanently sufficient energy for the evaporation process, especially when concentrating volumes of 10 ml or more. If the only heated part is the wall of the centrifuge, after couple of minutes the samples cool down to very low temperatures, and the evaporation process slows down. A more efficient way to supply evaporation energy is by means of IR radiation. A very modern device offers an electronically controlled IR radiation by means of temperature control on the centrifugal tubes. This in combination with vapour pressure control ensures an optimal control of the most important factors of the evaporation process.