Characterizing the self‐potential response to concentration gradients in heterogeneous subsurface environments

Self‐potential (SP) measurements can be used to characterize and monitor, in real‐time, fluid movement and behavior in the subsurface. The electrochemical exclusion‐diffusion (EED) potential, one component of SP, arises when concentration gradients exist in porous media. Such concentration gradients are of concern in coastal and contaminated aquifers and oil and gas reservoirs. It is essential that estimates of EED potential are made prior to conducting SP investigations in complex environments with heterogeneous geology and salinity contrasts, such as the UK Chalk coastal aquifer. Here we report repeatable laboratory estimates of the EED potential of chalk and marls using natural groundwater (GW), seawater (SW), deionized (DI) water, and 5 M NaCl. In all cases, the EED potential of chalk was positive (using a GW/SW concentration gradient the EED potential was ca. 14 to 22 mV), with an increased deviation from the diffusion limit at the higher salinity contrast. Despite the relatively small pore size of chalk (ca. 1 μm), it is dominated by the diffusion potential and has a low exclusion efficiency, even at large salinity contrasts. Marl samples have a higher exclusion efficiency which is of sufficient magnitude to reverse the polarity of the EED potential (using a GW/SW concentration gradient the EED potential was ca. −7 to −12 mV) with respect to the chalk samples. Despite the complexity of the natural samples used, the method produced repeatable results. We also show that first order estimates of the exclusion efficiency can be made using SP logs, supporting the parameterization of the model reported in Graham et al. (2018, https://doi.org/10.1029/2018WR022972), and that derived values for marls are consistent with the laboratory experiments, while values derived for hardgrounds based on field data indicate a similarly high exclusion efficiency. While this method shows promise in the absence of laboratory measurements, more rigorous estimates should be made where possible and can be conducted following the experimental methodology reported here

The development of direct extrusion-injection moulded zein matrices as novel oral controlled drug delivery systems

Purpose: To evaluate the potential of zein as a sole excipient for controlled release formulations prepared by hot melt extrusion. Methods: Physical mixtures of zein, water and crystalline paracetamol were hot melt extruded (HME) at 80°C and injection moulded (IM) into caplet forms. HME-IM Caplets were characterised using differential scanning calorimetry, ATR-FTIR spectroscopy, scanning electron microscopy and powder X-ray diffraction. Hydration and drug release kinetics of the caplets were investigated and fitted to a diffusion model. Results: For the formulations with lower drug loadings, the drug was found to be in the non-crystalline state, while for the ones with higher drug loadings paracetamol is mostly crystalline. Release was found to be largely independent of drug loading but strongly dependent upon device dimensions, and predominately governed by a Fickian diffusion mechanism, while the hydration kinetics shows the features of Case II diffusion. Conclusions: In this study a prototype controlled release caplet formulation using zein as the sole excipient was successfully prepared using direct HME-IM processing. The results demonstrated the unique advantage of the hot melt extruded zein formulations on the tuneability of drug release rate by alternating the device dimensions

Welche unerwünschten Ereignisse haben einen Einfluss auf die Behandlungsabbruchrate von selektiven Serotonin-Wiederaufnahmehemmern (SSRI)? Ergebnis von 50.824 Patienten

Background: Nowadays, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants due to their superior clinical efficacy, effectiveness, tolerability, and safety as compared to tricyclic antidepressants or monoamino oxidase inhibitors. However, despite these advantages SSRIs are still associated with a number of adverse drug reactions, especially in the early stages of treatment, which may lead to premature discontinuation of therapy in some cases. The aim of the present study was to assess the most common adverse drug reactions of SSRIs as well as their impact on dropout rate in a large study population.Patients and methods: Data for 50,824 patients treated for major depressive disorder with SSRIs for the first time was accessed via the Disease Analyzer database (IMS Health, Germany), providing information on SSRI adverse drug reactions and their influence on premature treatment discontinuation calculated by regression analysis. The presence of certain co-morbidities was also registered. Results: The mean age was 54.5 ± 19 years, two-thirds of the study population being female. The adverse effects mentioned most frequently were: "discomfort" of the digestive system (10%), sleep disorders (8.6%), and heart rhythm disorders (4%); however, these were of tolerable severity as they did not significantly influence the dropout rate. Contrary to that, somnolence and younger age (<=50 years) in particular increased the chance of premature treatment discontinuation, while patients suffering from cardiovascular risk factors or osteoporosis tended to adhere to the therapy.Conclusions: Overall, there is high tolerability for early SSRI treatment, whereas the occurrence of somnolence leads to discontinuation.Hintergrund: Heutzutage sind Serotonin-Wiederaufnahmehemmer (SSRI) aufgrund ihrer verglichen mit trizyklischen Antidepressiva oder Monoamino-Oxidase-Inhibitoren überlegenen klinischen Wirksamkeit, Verträglichkeit und Sicherheit die meistverschriebenen Antidepressiva. Dennoch sind trotz dieser Vorteile SSRIs mit einer Vielzahl an unerwünschten Arzneimittelnebenwirkungen verbunden, insbesondere im frühen Stadium der Behandlung, was in manchen Fällen zu einem verfrühtem Therapieabbruch führen kann. Das Ziel der vorliegenden Studie war es die meisten unerwünschten Arzneimittelnebenwirkungen von SSRIs zu erfassen sowie die Auswirkung auf die Behandlungsabbruchrate in einer großen Population zu ermitteln.Patienten und Methoden: Daten von 50.824 Patienten mit einer SSRI-Erstbehandlung einer schweren depressiven Störung wurden über die IMS (R) Disease Analyzer Datenbank (IMS Health) retrospektiv analysiert, wobei Informationen über unerwünschte SSRI-Nebenwirkungen und deren Einfluss auf einen verfrühten Therapieabbruch über Regressionsanalysen ermittelt wurden. Das Auftreten von bestimmten Co-Morbiditäten wurden ebenfalls registriert.Ergebnisse: Das mittlere Alter war 54.5 (±19) Jahre, zwei Drittel der Population waren weiblich. Die meist dokumentierten unerwünschten Nebenwirkungen waren: Beschwerden des Verdauungssystems (10%), Schlafstörung (8.6%) und Herzrhythmusstörung (4%); diese waren allerdings von erträglichem Ausmaß, da dadurch die Drop-Out-Rate nicht signifikant beeinflusst wurde. Hingegen erhöht insbesondere Somnolenz als Nebenwirkung und jüngeres Alter (<=50 Jahre) die Wahrscheinlichkeit eines vorzeitigen Therapieabbruchs, während Patienten mit kardiovaskulären Risikofaktoren oder Osteoporose die Tendenz aufweisen die Therapie aufrechtzuerhalten. Schlussfolgerung: Insgesamt wurde eine gute Verträglichkeit der SSRI-Behandlung nachgewiesen, wohingegen das Auftreten von Somnolenz zu einem Therapieabbruch führte