Influence of process variables on the properties of simvastatin self-emulsifying granules obtained through high shear wet granulation

Improvements of the oral bioavailability of lipophilic drugs can be obtained using lipidic formulations such as the self-emulsifying drug delivery systems. The high shear wet granulation (HSWG), using microemulsions as binder, is a viable process to produce self-emulsifying granules. However only few information are present in the literature on the effect of process variables on the properties of the granules obtained with these binders. Consequently, this article compares the effects of some relevant experimental variables (impeller speed and massing time) on thefinal technological and pharmaceutical properties of the granules produced using simple water, or alternatively, a microemulsion as binder and containing simvastatin (SV) as model drug. The effects of the variables were determined by evaluating the granule median diameter, their particle size distribution, roundness, disintegration time and dissolution rate of SV. Results clearly demonstrated that the microemulsion-based process was less sensitive tooperating conditions than the water-based process. With microemulsion the nucleation process and growth regimes were more difficult to control, resulting in products with broader PSDs. At the same operatingconditions microemulsion-based granules were more brittle but rounder and showed smaller median diameter compared to water-based granules. The dissolution rate of simvastatin was not significantly affected by the operating conditions

Rapidly-Disintegrating Laminar Extrudates: Preliminary Experiments upon an Age Appropriate Pediatric Formulation

The aim of the present investigation is to produce rapidly disintegrating laminar extrudates for delivering ibuprofen in the mouth of paediatric patients. This laminar shape is particularly convenient for drug delivering in the mouth and can be easily cut in cut in different sizes allowing for a convenient adjustment of the drug dose depending on the age of the patient. Due to the fact that in paediatric formulations, the selection of the excipients is always a challenging issue and the reduction of their amount is always highly desirable, in this study to select the most appropriate composition to achieve a rapid disintegration and simultaneously permit a high amount of ibuprofen in the system, an experimental design for mixtures was employed and the disintegration time in simulated saliva was used as experimental response. In addition, after solid state analyses to check possible insurgence of drug-excipients interactions, laminar extrudates were characterised in terms of mechanical properties and in vitro dissolution performances. Extrudates with the desired uniform laminar shape, constant thickness (2 mm) and a very high content of drug (82% wt) were produced. These products exhibited a short disintegration time. The dose for a patient of 6-12 years corresponded to a length of extrudate between 1-1.5 cm, perfectly compatible with a formulation orodispersible thin laminar extrudate intended for a paediatric patient (Figure 1)

Evidence-Based Analysis of Cyber Attacks to Security Monitored Distributed Energy Resources

This work proposes an approach based on dynamic Bayesian networks to support the cybersecurity analysis of network-based controllers in distributed energy plants. We built a system model that exploits real world context information from both information and operational technology environments in the energy infrastructure, and we use it to demonstrate the value of security evidence for time-driven predictive and diagnostic analyses. The innovative contribution of this work is in the methodology capability of capturing the causal and temporal dependencies involved in the assessment of security threats, and in the introduction of security analytics supporting the configuration of anomaly detection platforms for digital energy infrastructures

Grandes anomalías en la declinación paleomagnética en la isla Cerro Nevado, Península Antártica ¿evidencia de rotaciones tectónicas ocultas?

Estudios magnetoestratigráficos realizados en las sedimentitas cretácicas marinas del Grupo Marambio en el sector sudeste de la cuenca James Ross, arrojaron direcciones paleomagnéticas anómalas para el nunatak Sanctuary Cliffs y la península Spath (isla Cerro Nevado). La calidad de los datos y las pruebas de campo sugieren que la magnetización es de origen primario y que no fue afectada por procesos de alteración o remagnetización relacionados con la posterior actividad magmática. La variación en la declinación encontrada para el Cretácico de la isla Cerro Nevado se puede explicar a partir de una rotación tectónica antihoraria calculada en 47.9° ± 20.0°. La actitud de los estratos cretácicos en las localidades de muestreo, con rumbos que presentan variaciones en la misma dirección que la dirección paleomagnética, es consistente con esta interpretación. Sin embargo, la continuidad geológica que se observa entre las unidades aflorantes de la isla Marambio (Seymour) y de la península Spath, sumado a las variaciones locales de rumbo dentro de la propia isla, limita una hipotética rotación de un bloque rígido que comprenda a toda la isla a un máximo de ~10° alrededor de un eje vertical ubicado en el Pasaje Picnic (~64.4°S, 56.9°O). Esto permite inferir que las hipotéticas rotaciones sugeridas por los datos paleomagnéticos debieron ocurrir durante el Eoceno, previamente a la estructuración de las unidades cretácicas. Este modelo requiere ser validado con nuevos estudios geológicos, paleomagnéticos y geofísicos en Cerro Nevado y en sus áreas marítimas vecinas.We report anomalous paleomagnetic directions obtained in magnetostratigraphic studies carried out on Cretaceous marine sedimentary rocks of the Marambio Group, southeast James Ross Basin, at the Sanctuary Cliffs Nunatak and the Spath Peninsula, located in the Cerro Nevado (Snow Hill) Island. Data quality and field tests suggest a primary origin of the magnetization, ruling out the possibility that directions have been affected by alteration or remagnetization processes related to the Miocene magmatism of the James Ross Island Volcanic Group. A counterclockwise tectonic rotation of 47.9° ± 20.0° of the whole Cerro Nevado Island can account for the paleomagnetic declination anomaly. The bedding of the Cretaceous units at and near the sampling localities show similar directional variations that those observed in paleomagnetic declinations, consistent with such interpretation. However, geological continuity between the exposed units at Marambio Island and the Spath Peninsula, the variable bedding strikes at different localities in the Cerro Nevado Island, plus geometric considerations strongly constrain any rigid body counterclockwise rotation of the whole island to a maximum of about 10°, around a vertical axis located close to the Picnic Passage (~64.4°S, 56.9°W). This indicates that most, if not all, of the hypothetical rotations suggested by the paleomagnetic data must occurred during the Eocene, before tectonic tilting of the Cretaceous units. This needs to be tested with new detailed structural and paleomagnetic studies at different localities along the Cerro Nevado Island as well as with geophysical surveys along the island and its marine surroundings.Fil: Milanese, Florencia Nidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Rapalini, Augusto Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Gallo, Leandro César. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Franceschinis, Pablo Reinaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Kirschvink, Joseph L.. California Institute of Technology; Estados Unidos. Tokyo Institute of Technology; Japó

Identification of maladaptive behavioural patterns in response to extreme weather events

Human behaviour has gained recognition as a critical factor in addressing climate change and its impacts. With extreme weather events posing risks to vulnerable communities, understanding cognitive processes driving behaviours becomes essential for effective risk communication. This study focuses on the 2018 "Vaia" storm, which brought unprecedented precipitation and wind velocity to the mountainous regions of North-eastern Italy. Drawing upon the Protection Motivation Theory (PMT) framework, we employ probabilistic models to identify distinct groups with similar behavioural profiles. By administering a web-based survey to 1500 residents affected by the event, we find that threat appraisal is more influential in shaping protective behaviours than coping appraisal. Our findings indicate that by enhancing coping appraisals and discouraging non-protective measures, we can actively mitigate maladaptive responses and promote the adoption of effective adaptation strategies

Multiple sclerosis disease: A computational approach for investigating its drug interactions

Multiple Sclerosis (MS) is a chronic and potentially highly disabling disease that can cause permanent damage and deterioration of the central nervous system. In Europe it is the leading cause of non-traumatic disabilities in young adults, since more than 700,000 EU people suffer from MS. Although recent studies on MS pathophysiology have been performed, providing interesting results, MS remains a challenging disease. In this context, thanks to recent advances in software and hardware technologies, computational models and computer simulations are becoming appealing research tools to support scientists in the study of such disease. Motivated by this consideration, we propose in this paper a new model to study the evolution of MS in silico, and the effects of the administration of the daclizumab drug, taking into account also spatiality and temporality of the involved phenomena. Moreover, we show how the intrinsic symmetries of the model we have developed can be exploited to drastically reduce the complexity of its analysis

Foam-Mat Freeze-Drying of Blueberry Juice by Using Trehalose-β-Lactoglobulin and Trehalose-Bovine Serum Albumin as Matrices

This study aimed to evaluate the effect of pure protein compounds and trehalose incorporated into blueberry juice for foam-mat freeze-drying on the foam and powder properties. Foam-mat freeze-drying (FMFD) of blueberry juice was tested at − 55 °C for 24 h. Matrices used were trehalose + β-lactoglobulin (T3BL1) and trehalose + bovine serum albumin (T3A1) and compared with maltodextrin + whey protein isolate (M3W1). Physicochemical properties of foam and powder, e.g., foam stability, foam density, moisture, rehydration time, color, particle morphology, total phenolic, and anthocyanins (total and individuals), were investigated. T3BL1 and T3A1 had more stable foam than M3W1. However, overrun of T3BL1 and T3A1 foamed were inferior to the M3W1 sample. The M3W1 sample recovered 79% powder (dry weight) and was superior to others. Rehydration time of powdered T3BL1 and T3A1, with bulk densities of 0.55–0.60 g cm−3, was the fastest (34–36 s). The blueberry powders of M3W1 showed more irregular particle size and shape, while the samples with trehalose and pure proteins generated particles of more uniform size with obvious pores. T3BL1 and T3A1 showed less redness (a*) values than the M3W1 product. All samples were considered pure red due to hue values < 90. M3W1 was superior in total phenolic content (TPC) and total monomeric anthocyanins (TMA) compared with both samples made with trehalose + β-lactoglobulin and trehalose+bovine serum albumin. Delphinidin-3-glucoside (Del3Gl) concentration was found to be higher in M3W1. Also, M3W1 had higher cyanidin-3-glucoside (Cyn3Gl) and malvidin-3-glucoside (Mal3Gl) concentration. M3W1 also prevented the degradation of these bioactive compounds better than the other FMFD samples. The use of pure proteins and trehalose as matrices in the FMFD process had little advantage compared with maltodextrin/whey protein isolate. Thus, maltodextrin/whey protein isolate seems an ideal matrix for the manufacture of FMFD blueberry

Performance and dependability analysis of fault-tolerant memory mechanisms using stochastic well-formed nets

This paper presents a performance and dependability study of a software fault-tolerant memory mechanism, namely the Distributed Memory (DM), which has been developed within a R&D European project. Relying on the UML specification (produced within the project), Stochastic Well-Formed Nets models of the DM are developed and analysed. Combinatorial methods are used in conjunction with state space based methods to study the impact of the mechanism configuration on its reliability and performance