MULTI-COMPONENT MICROPARTICULATE/NANOPARTICULATE DRY POWDER INHALATION AEROSOLS FOR TARGETED PULMONARY DELIVERY

The aim of the work was to design, manufacture, and characterize targeted multi-component dry powder aerosols of (non-destructive) mucolytic agent (mannitol), antimicrobial drug (tobramycin or azithromycin), and lung surfactant mimic phospholipids (DPPC:DPPG=4:1 in molar ratio). The targeted dry powder for inhalation formulation for deep lung delivery with a built-in rationale of specifically interfering several disease factors of chronic infection diseases in deep lungs such as cystic fibrosis, pneumonia, chronic bronchitis, and etc. The dry powder aerosols consisting of selected chemical agents in one single formulation was generated by using spray drying from organic solution. The physicochemical properties of multi-component dry powder inhaler (DPI) formulation were characterized by a number of techniques. In addition, the in vitro aerosol dispersion performance, storage stability test, and in vitro drug release of selected spray-dried (SD) multi-component systems were conducted. The physicochemical study revealed that multi-component aerosol particles possessed essential particle properties suitable for deep lung delivery. In general, the multi-component particles (typically 0.5 to 2 µm) indicated that the designed SD aerosol particles could potentially penetrate deep lung regions (such as respiratory bronchiolar and alveolar regions) by sedimentation and diffusion, respectively. The essential particle properties including narrow size distribution, spherical particle and smooth surface morphologies, and low water content (or water vapor sorption) could potentially minimize interparticulate interactions. The study of in vitro aerosol dispersion performance showed that majority of SD multi-component aerosols exhibited low values (less than 5µm) of MMAD, high values (approximately above 30% up to 60.4%) of FPF, and high values (approximately above 90%) of ED, respectively. The storage stability study showed that azithromycin–incorporated multi-component aerosol particles stored at 11 and 40% RH with no partial crystallization were still suitable for deep lung delivery. Compared to SD pure azithromycin particles, the azithromycin-incorporated multi-component particles exhibited an enhanced initial release. The targeted microparticulate and nanoparticulate multi-component dry powder aerosol formulations with essential particle properties for deep lung pulmonary delivery were successfully produced by using spray drying from organic solution. The promising experimental data suggest the multi-component formulations could be further investigated in in vivo studies for the purpose of commercialization

Evolution of the dispersionless injection boundary associated with substorms

International audienceOne manifestation of energetic particle acceleration during magnetospheric substorms is the sudden appearance of particle injections into the inner magnetosphere, often observed near geosynchronous orbit. Injections that show simultaneous flux increases in all energy ranges of a detector are called dispersionless injections, and are most often observed in a narrow region around local midnight. In these events it is assumed that the satellite is located close to or inside the region where acceleration and/or transport processes are taking place, called the injection region. We present a study of the location, extent and temporal evolution of the injection region, based on simulation results of a model of the expansion of the electric and magnetic fields associated with a substorm. The model simulates the fields during a substorm onset with an electric field and consistent magnetic field pulse that propagates towards the Earth with a decreasing speed. Our simulation shows that the dispersionless injection boundary can be considered coincident with the leading edge of the pulse field, which transports particles toward the Earth across a certain range of local time. Under the same model field, the dispersionless injection boundary shifts eastward for electrons and westward for protons, consistent with the observation results deduced from statistical analysis of multiple spacecraft measurements

Information Disclosure and Consumer Awareness

Whether consumers are aware of potentially adverse product effects is key to private and social incentives to disclose information about undesirable product characteristics. In a monopoly model with a mix of aware and unaware consumers, a larger share of unaware consumers makes information disclosure less likely to occur. Since the firm is not interested in releasing information to unaware consumers, a more precise targeting technology that allows the firm to better keep unaware consumers in the dark leads to more disclosure. A regulator may want to intervene in this market and impose mandatory disclosure rules

Multi-point and multi-objective optimization of a centrifugal compressor impeller based on genetic algorithm

The design of high efficiency, high pressure ratio, and wide flow range centrifugal impellers is a challenging task. The paper describes the application of a multiobjective, multipoint optimization methodology to the redesign of a transonic compressor impeller for this purpose. The aerodynamic optimization method integrates an improved nondominated sorting genetic algorithm II (NSGA-II), blade geometry parameterization based on NURBS, a 3D RANS solver, a self-organization map (SOM) based data mining technique, and a time series based surge detection method. The optimization results indicate a considerable improvement to the total pressure ratio and isentropic efficiency of the compressor over the whole design speed line and by 5.3% and 1.9% at design point, respectively. Meanwhile, surge margin and choke mass flow increase by 6.8% and 1.4%, respectively. The mechanism behind the performance improvement is further extracted by combining the geometry changes with detailed flow analysis

Simulating radial diffusion of energetic (MeV) electrons through a model of fluctuating electric and magnetic fields

International audienceIn the present work, a test particle simulation is performed in a model of analytic Ultra Low Frequency, ULF, perturbations in the electric and magnetic fields of the Earth's magnetosphere. The goal of this work is to examine if the radial transport of energetic particles in quiet-time ULF magnetospheric perturbations of various azimuthal mode numbers can be described as a diffusive process and be approximated by theoretically derived radial diffusion coefficients. In the model realistic compressional electromagnetic field perturbations are constructed by a superposition of a large number of propagating electric and consistent magnetic pulses. The diffusion rates of the electrons under the effect of the fluctuating fields are calculated numerically through the test-particle simulation as a function of the radial coordinate L in a dipolar magnetosphere; these calculations are then compared to the symmetric, electromagnetic radial diffusion coefficients for compressional, poloidal perturbations in the Earth's magnetosphere. In the model the amplitude of the perturbation fields can be adjusted to represent realistic states of magnetospheric activity. Similarly, the azimuthal modulation of the fields can be adjusted to represent different azimuthal modes of fluctuations and the contribution to radial diffusion from each mode can be quantified. Two simulations of quiet-time magnetospheric variability are performed: in the first simulation, diffusion due to poloidal perturbations of mode number m=1 is calculated; in the second, the diffusion rates from multiple-mode (m=0 to m=8) perturbations are calculated. The numerical calculations of the diffusion coefficients derived from the particle orbits are found to agree with the corresponding theoretical estimates of the diffusion coefficient within a factor of two

Worried about Adverse Product Effects? Information Disclosure and Consumer Awareness

Whether consumers are aware of potentially adverse product effects, is key for private and social incentives to disclose information. To obtain a better understanding of this issue we propose a simple monopoly model that highlights the conceptual difference between consumer unawareness and consumer uncertainty. We show that total surplus may be larger in an environment in which consumers are unaware of the potentially adverse effect. We also show that disclosing information whether a particular ingredient is harmful or not increases consumer surplus, but mandatory disclosure of the level of this ingredient may make consumers worse off

Worried about Adverse Product Effects? Information Disclosure and Consumer Awareness

Whether consumers are aware of potentially adverse product effects, is key for private and social incentives to disclose information. To obtain a better understanding of this issue we propose a simple monopoly model that highlights the conceptual difference between consumer unawareness and consumer uncertainty. We show that total surplus may be larger in an environment in which consumers are unaware of the potentially adverse effect. We also show that disclosing information whether a particular ingredient is harmful or not increases consumer surplus, but mandatory disclosure of the level of this ingredient may make consumers worse off