Effect of Cryogrinding on Chemical Stability of the Sparingly Water-Soluble Drug Furosemide

Purpose To investigate the effect of cryogrinding on chemical stability of the diuretic agent furosemide and its mixtures with selected excipients. Methods Furosemide was ground at liquid nitrogen temperature for 30, 60, 120 and 180 min. Mixtures of furosemide-PVP and furosemide-inulin (1:1) were milled under cryogenic conditions. Materials were analyzed by XRD, UPLC, MS and NMR. Results Upon increasing the milling time, a significant build-up of an unidentified impurity 1, probably the main degradation product, was noticed. Cogrinding of furosemide with PVP and inulin worsened chemical stabilization of the pharmaceutical. The main degradation product formed upon cryomilling was subsequently identified as 4-chloro-5-sulfamoylanthranilic acid (CSA). Based on some theoretical considerations involving specific milling conditions, the milling intensity and an expected specific milling dose have been calculated. Results indicate that cryogenic grinding is capable to initiate mechanically induced decomposition of furosemide.Conclusions Cryogenic grinding can activate and accelerate not only structural changes (solid state amorphization) but also chemical decomposition of pharmaceuticals. A cryogenic milling device should be considered as a chemical reactor, where under favourable conditions chemical reactions could be mechanically initiated

Thermoluminescence du quartz naturel et artificiel pur ou dopé avec des ions Fe++ et Fe+++. Application à la datation des poteries

The thermoluminescence observed on samples of pottery and leading to their archeological dating is a result of the presence of quartz particles originally enclosed in the clay. We offer a study of the thermoluminescence of samples of synthetic mono-crystalline quartz doped in with impurities and apply the results to a new dating technique, the “DATE” method, based upon difference in time attenuation of the emissions.La thermoluminescence constatée sur les échantillons de poteries et conduisant à la datation archéologique de celles-ci, est due aux inclusions de quartz initialement contenues dans l’argile. Nous présentons une étude de la thermoluminescence d’échantillons de quartz monocristallin synthétique dans lesquels des impuretés ont été volontairement ajoutées et appliquons les résultats â une nouvelle technique de datation, la méthode DATE (différence d'atténuation temporelle des émissions).La termoluminiscencia constatada en muestras de cerámica permite una datación arqueológica; es debida a las inclusiones de cuarzo inicialmente contenidas en la arcilla. Se presenta un estudio de la termoluminiscencia de muestras de cuarzo monocristalino sintético en las cuales han sido colocadas voluntariamente impurezas; se han aplicado los resultados de una nueva técnica de fechado, el método DATE (Diferencia de atenuación temporal de emisiones).Roman A., Decamps E. A. Thermoluminescence du quartz naturel et artificiel pur ou dopé avec des ions Fe++ et Fe+++. Application à la datation des poteries. In: Bulletin de l'Institut Français d’Études Andines, tome 7, N°3-4, 1978. pp. 153-164

Corporate Policies with Temporary and Permanent Shocks

International audienceWe model the financing, cash holdings, and hedging policies of a firm facing financing frictions and subject to permanent and transitory cash flow shocks. The permanent and transitory shocks generate distinct, sometimes opposite, effects on corporate policies. We use the model to develop a rich set of empirical predictions. In our model, correlated permanent and transitory shocks imply less risk, lower cash savings, and a drop in the value of credit lines. The composition of cash-flow shocks affects the cash-flow sensitivity of cash, which can be positive or negative. Optimal hedging of permanent and transitory shocks may involve opposite position

Datation par thermoluminescence

Since 1953, a number of scientists have been concerned with the use of thermoluminescence for the dating of burned or fired minerals. After recalling some of the physical principles of thermoluminescence, this paper describes that dating process with emphasis upon the working of the thermoluminescent phenomenon in a piece of earthenware. The dose of irradiation received by the material being in direct ratio to the time elapsed since the "archeological zero", it is possible to determine the "archeological dose" and, after calculating the annual dose of irradiation, infer from it the age of the sample. Practically, however, carrying out such a set of measurements is arduous matter. In a forthcoming paper, E. A. Decamps and A. Roman will present some results about the thermoluminescence of samples of pure or doped natural quartz and the perfecting of a new dating process.Depuis 1953, de nombreux chercheurs se sont intéressés à la datation par thermoluminescence de minéraux anciennement brûlés ou cuits. Dans ce travail, après avoir rappelé quelques principes physiques de la thermoluminescence, on présente cette méthode de datation en mettant l'accent sur le mécanisme thermoluminescent dans une poterie. Ainsi la dose d’irradiation reçue par le matériau étant proportionnelle au temps écoulé depuis le "zéro archéologique", il est possible de déterminer "la dose archéologique" et d'en déduire l'âge de l’échantillon après avoir calculé la dose d’irradiation annuelle. La réalisation pratique d’un tel ensemble de mesure est cependant très ardue. Dans un prochain article, E. A. Decamps et A. Roman montreront des résultats relatifs à la thermoluminescence d’échantillons de quartz naturels, purs et dopés et la mise au point d’une nouvelle méthode de datation.Desde 1953, muchos investigadores se han interesado en la datación por termoluminiscencia de minerales antiguamente quemados o cocidos. Dentro de este trabajo, luego de haber recordado algunos principios físicos de la termoluminiscencia, se presenta este método de datación poniendo mayor atención en el mecanismo termoluminiscente en una vasija de metal o de barro. Siendo proporcional la dosis de irradiación recibida al tiempo transcurrido desde el "cero arqueológico", es posible determinar "la dosis arqueológica", y deducir la edad de la muestra luego de haber calculado la dosis de irradiación anual. La realización práctica de un trabajo de tal dimensión es sin embargo muy ardua. En un próximo artículo, E. A. Decamps y A. Roman presentarán los resultados relativos a la termoluminiscencia de muestras de cuarzo naturales, puras y dopadas y la elaboración de un nuevo método de datación.Abba F., Decamps E. A., Brun Patrice, Bombre F. Datation par thermoluminescence. In: Bulletin de l'Institut Français d’Études Andines, tome 5, N°3-4, 1976. pp. 91-104

Radiation-induced bcc-fcc phase transformation in a Fe-3%Ni alloy

International audienceThe issue of neutron irradiation embrittlement of Reactor Pressure Vessel steels must be considered for Nuclear Power Plant life extension. This phenomenon partly arises from the existing interactions between dislocations and nanometric clusters composed of Cu, P, Si, Mn and Ni. The latter alloying element, playing a key role in the evolution of solute enriched clusters under irradiation, is the focus of this publication. To assess the effect of Ni on microstructure evolution under irradiation, particle accelerator based experiments were conducted. An under-saturated Fe3at.%Ni alloy was irradiated with self-ions, at 673 K, up to ∼1.2 dpa. Then, the microstructural damage was characterized, at the atomic scale, by conventional Transmission Electron Microscopy, Scanning Transmission Electron Microscopy coupled to Energy Dispersive X-ray Spectroscopy and Electron Energy Loss Spectroscopy, while chemical features were investigated by Atom Probe Tomography. Informations obtained by combining these coupled techniques provide evidence for the formation of a FCC phase, containing 25 at.%Ni, which can be either the disordered γ phase or the ordered L12 type Fe3Ni phase. The metastable or stable state of this FCC phase is discussed in the light of what is known from the literature. It is the first time that this BCC-FCC phase transformation is observed in an under-saturated α-FeNi alloy and this likely occurred via a Radiation Induced Precipitation (RIP) mechanism. Ni atom segregation is observed on cavities, dislocation lines and dislocation loops. The latter constitute nuclei for precipitates, leading to the formation of an additional segregation site for Ni: the precipitate FCC - matrix BCC nearly coherent interface. Similar mechanisms are argued to be operating also in high Ni RPV steels under neutron irradiation