Focusing of high-energy particles in the electrostatic field of a homogeneously charged sphere and the effective momentum approximation

The impact of the strongly attractive electromagnetic field of heavy nuclei on electrons in quasi-elastic (e,e') scattering is often accounted for by the effective momentum approximation. This method is a plane wave Born approximation which takes the twofold effect of the attractive nucleus on initial and final state electrons into account, namely the modification of the electron momentum in the vicinity of the nucleus, and the focusing of electrons towards the nuclear region leading to an enhancement of the corresponding wave function amplitudes. The focusing effect due to the attractive Coulomb field of a homogeneously charged sphere on a classical ensemble of charged particles incident on the field is calculated in the highly relativistic limit and compared to results obtained from exact solutions of the Dirac equation. The result is relevant for the theoretical foundation of the effective momentum approximation and describes the high energy behavior of the amplitude of continuum Dirac waves in the potential of a homogeneously charged sphere. Our findings indicate that the effective momentum approximation is a useful approximation for the calculation of Coulomb corrections in (e,e') scattering off heavy nuclei for sufficiently high electron energies and momentum transfer.Comment: 16 pages, 9 figures, LATEX, some references adde

Evolved gas analysis during thermal degradation of salbutamol sulphate

Crystalline salbutamol sulphate (SS) is a common β2-agonist used in dry powder inhalers for the treatment of asthma. The solid-state characteristics of SS are import since they govern the stability, and thus efficacy of the drug when incorporated in inhalation medicine. Previous studies have investigated the thermal properties of SS and the complex array of thermal events have been attributed a mixture of melting and/or degradation mechanisms. In order to ascertain the exact thermal transformation processes that SS undergoes, and we utilised a combination of differential scanning calorimetry coupled with quadrupole mass spectrometry and thermogravimetric analysis coupled with Fourier transform infrared spectroscopy over the temperature range 25-500 °C. Based on the coupled thermal analysis data, we proposed that SS undergoes a multi-step degradation mechanism in which the molecule dehydrates loosing water initially, followed by the break up of the secondary amine group and lastly formation of sulphur dioxide. When used in conjunction, the analytical techniques offered significant advantages over the use of thermal analysis alone, offering a better understanding of the transformations occurring to SS following heating

Ciprofloxacin is actively transported across bronchial lung epithelial cells using a calu-3 air interface cell model

Ciprofloxacin is a well-established broad-spectrum fluoroquinolone antibiotic that penetrates well into the lung tissues; still, the mechanisms of its transepithelial transport are unknown. The contributions of specific transporters, including multidrug efflux transporters, organic cation transporters, and organic anion-transporting polypeptide transporters, to the uptake of ciprofloxacin were investigated in vitro using an air interface bronchial epithelial model. Our results demonstrate that ciprofloxacin is subject to predominantly active influx and a slight efflux component. Copyright © 2013, American Society for Microbiology. All Rights Reserved

Comparison of albuterol sulphate and base dry powder particulate deposition using the Calu-3 lung epithelial model

To effectively predict the fate of formulated inhalation compounds delivered to the lung, a model of the airway epithelium should reflect drug permeability and transport characteristics in vivo. Most cell-based system established for this purpose, study drug transport using wet models and thus do not necessarily represent in vivo conditions. Recently, air-interface models have been established that increase the relevance of in vitro transport studies to the in vivo state. The aim of our study was to elucidate the dissolution and diffusion process of deposited dry drug particulates (albuterol) after aerosolization onto the epithelial surface and compare these to conventional in vitro `glass models. Two forms of albuterol were investigated (albuterol base and albuterol sulphate), to evaluate the effects of lipophilicity and aqueous solubility on the mechanism of transport

Approximate treatment of electron Coulomb distortion in quasielastic (e,e') reactions

In this paper we address the adequacy of various approximate methods of including Coulomb distortion effects in (e,e') reactions by comparing to an exact treatment using Dirac-Coulomb distorted waves. In particular, we examine approximate methods and analyses of (e,e') reactions developed by Traini et al. using a high energy approximation of the distorted waves and phase shifts due to Lenz and Rosenfelder. This approximation has been used in the separation of longitudinal and transverse structure functions in a number of (e,e') experiments including the newly published 208Pb(e,e') data from Saclay. We find that the assumptions used by Traini and others are not valid for typical (e,e') experiments on medium and heavy nuclei, and hence the extracted structure functions based on this formalism are not reliable. We describe an improved approximation which is also based on the high energy approximation of Lenz and Rosenfelder and the analyses of Knoll and compare our results to the Saclay data. At each step of our analyses we compare our approximate results to the exact distorted wave results and can therefore quantify the errors made by our approximations. We find that for light nuclei, we can get an excellent treatment of Coulomb distortion effects on (e,e') reactions just by using a good approximation to the distorted waves, but for medium and heavy nuclei simple additional ad hoc factors need to be included. We describe an explicit procedure for using our approximate analyses to extract so-called longitudinal and transverse structure functions from (e,e') reactions in the quasielastic region.Comment: 30 pages, 8 figures, 16 reference

Are There Diquarks in the Nucleon?

This work is devoted to the study of diquark correlations inside the nucleon. We analyze some matrix elements which encode information about the non-perturbative forces, in different color anti-triplet diquark channels. We suggest a lattice calculation to check the quark-diquark picture and clarify the role of instanton-mediated interactions. We study in detail the physical properties of the 0+ diquark, using the Random Instanton Liquid Model. We find that instanton forces are sufficiently strong to form a diquark bound-state, with a mass of ~500 MeV, which is compatible with earlier estimates. We also compute its electro-magnetic form factor and find that the diquark is a broad object, with a size comparable with that of the proton.Comment: Final version, accepted for publication on Phys. Rev.

Determination of physical and chemical stability in pressurised metered dose inhalers: potential new techniques

INTRODUCTION: Pressurised metered dose inhalers (pMDIs) are subject to rigorous physical and chemical stability tests during formulation. Due to the time and cost associated with product development studies, there is a need for online techniques to fast screen new formulations in terms of physical and chemical (physico-chemical) stability. The problem with achieving this is that pMDIs are by their definition, pressurised, making the direct observation of physico-chemical properties in situ difficult. AREAS COVERED: This review highlights the characterisation tools that can enhance the product development process for pMDIs. Techniques investigated include: laser diffraction, Raman spectroscopy, isothermal ampoule calorimetry, titration calorimetry and gas perfusion calorimetry. The operational principles behind each technique are discussed and complemented with examples from the literature. EXPERT OPINION: Laser diffraction is well placed to analyse real-time physical stability as a function of particle size; however, its use is restricted to suspension pMDIs. Raman spectroscopy can be potentially used to attain both suspension and solution pMDI spectra in real time; however, the majority of experiments are ex-valve chemical composition mapping. Calorimetry is an effective technique in capturing both chemical and physical degradations of APIs in real time but requires redevelopment to withstand pressure for the purposes of pMDI screening

Delivery of high solubility polyols by vibrating mesh nebuliser to enhance mucociliary clearance

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Repurposing of statins via inhalation to treat lung inflammatory conditions

© 2018 Elsevier B.V. Despite many therapeutic advancements over the past decade, the continued rise in chronic inflammatory lung diseases incidence has driven the need to identify and develop new therapeutic strategies, with superior efficacy to treat these diseases. Statins are one class of drug that could potentially be repurposed as an alternative treatment for chronic lung diseases. They are currently used to treat hypercholesterolemia by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, that catalyses the rate limiting step in the mevalonate biosynthesis pathway, a key intermediate in cholesterol metabolism. Recent research has identified statins to have other protective pleiotropic properties including anti-inflammatory, anti-oxidant, muco-inhibitory effects that may be beneficial for the treatment of chronic inflammatory lung diseases. However, clinical studies have yielded conflicting results. This review will summarise some of the current evidences for statins pleiotropic effects that could be applied for the treatment of chronic inflammatory lung diseases, their mechanisms of actions, and the potential to repurpose statins as an inhaled therapy, including a detailed discussion on their different physical-chemical properties and how these characteristics could ultimately affect treatment efficacies. The repurposing of statins from conventional anti-cholesterol oral therapy to inhaled anti-inflammatory formulation is promising, as it provides direct delivery to the airways, reduced risk of side effects, increased bioavailability and tailored physical-chemical properties for enhanced efficacy