In vitro release and bioaccessibility of oral solid preparations in a dynamic gastrointestinal system simulating fasted and fed states: A case study of metformin hydrochloride tablets.

Food and formulation characteristics are crucial factors affecting the gastrointestinal release and absorption kinetics of oral solid preparations. In the present study, the dynamic continuous release and bioaccessibility of metformin hydrochloride immediate-release (IR) and sustained-release (SR) tablets were investigated in the dynamic human stomach-intestine (DHSI-IV) system simulating fasted and fed states in healthy adults. Both tablet formulations (particularly IR tablet) exhibited a postponed release in the fed state compared to the fasted state. Correspondingly, the bioaccessible fraction of metformin from IR tablets in the presence of high-fat meal was significantly reduced to 76.2 % of the fasted state. However, the in vitro bioaccessibility was less impaired by food for SR tablets with a fed/fasted ratio of 95.5 %. A convolution-based approach was used to convert in vitro bioaccessibility results to plasma concentration data. The predicted plasma concentration curve showed good agreement with human data in terms of pharmacokinetic (PK) parameters. In the fasted state, the predicted Cmax, Tmax and AUC0-24h of IR tablets were 943.9 ± 25.7 ng/mL, 2.0 ± 0.4 h and 7090.7 ± 112.0 ng.h/mL, respectively, mirroring values observed in healthy subjects. Overall, the DHSI-IV system has demonstrated potential to assess and predict the impact of meal intake on the in vivo release and absorption behaviors of oral solid preparations.

Extending Porous Silicone Capacitive Pressure Sensor Applications into Athletic and Physiological Monitoring.

Porous polymer dielectric materials have been developed to increase the sensitivity of capacitive pressure sensors, so that they might expand capacitive sensor use, and promote the realization of the advantages of this class of sensor in further fields. However, their use has not been demonstrated in physiological monitoring applications such as respiration monitoring and body position detection during sleep; an area in need of unmet medical attention for conditions such as sleep apnea. Here, we develop and characterize a sensor comprised of a poly dimethylsiloxane (PDMS) sponge dielectric layer, and PDMS/carbon black (CB) blend electrode layers, with suitable compliance and sensitivity for integration in mattresses, pillows, and athletic shoe insoles. With relatively high pressure sensitivity (~0.1 kPa-1) and mechanical robustness, this sensor was able to fulfill a wide variety of roles, including athletic monitoring in an impact mechanics scenario, by recording heel pressure during running and walking, and physiological monitoring, by detecting head position and respiration of a subject lying on a pad and pillow. The sensor detected considerably greater relative signal changes than those reported in recent capacitive sensor studies for heel pressure, and for a comparably minimal, resistive sensor during respiration, in line with its enhanced sensitivity.

Practical and Durable Flexible Strain Sensors Based on Conductive Carbon Black and Silicone Blends for Large Scale Motion Monitoring Applications.

Presented is a flexible capacitive strain sensor, based on the low cost materials silicone (PDMS) and carbon black (CB), that was fabricated by casting and curing of successive silicone layers-a central PDMS dielectric layer bounded by PDMS/CB blend electrodes and packaged by exterior PDMS films. It was effectively characterized for large flexion-angle motion wearable applications, with strain sensing properties assessed over large strains (50%) and variations in temperature and humidity. Additionally, suitability for monitoring large tissue deformation was established by integration with an in vitro digestive model. The capacitive gauge factor was approximately constant at 0.86 over these conditions for the linear strain range (3 to 47%). Durability was established from consistent relative capacitance changes over 10,000 strain cycles, with varying strain frequency and elongation up to 50%. Wearability and high flexion angle human motion detection were demonstrated by integration with an elbow band, with clear detection of motion ranges up 90°. The device's simple structure and fabrication method, low-cost materials and robust performance, offer promise for expanding the availability of wearable sensor systems.

Antagonismo del Sistema Endocanabinoide: Implicaciones en el tratamiento de la obesidad, síndrome metabólico y adición a drogas

Rimonabant (SR141716, Acomplia®) ha sido catalogado como un antagonista/agonista inverso del receptor canabinoide tipo 1 (CB1). Dicho compuesto ha sido ampliamente utilizado como una herramienta para evaluar los mecanismos mediante los cuales los agonistas canabinoides producen sus efectos farmacológicos y adicionalmente dilucidar los respectivos roles fisiológicos y fisiopatológicos del receptor CB1. Aparte del antagonismo a nivel del receptor CB1 reciente evidencia ha demostrado cada vez mas que rimonabant también es capaz de ejercer acciones por si mismo. Estas acciones pueden ser vistas como agonismo inverso o como antagonismo de un tono endocanabinoide endógeno que tiende variar según las circunstancias. Actualmente, dentro de los diferentes efectos de rimonabant, los que poseen mayor relevancia clínica son sus propiedades anti-obesidad y su capacidad de atenuar la dependencia a la nicotina. Los resultados obtenidos en estudios clínicos recientes han demostrado que el tratamiento con rimonabant produce perdida de peso en pacientes obesos. Adicionalmente rimonabant produce una normalización de los parámetros metabólicos y disminuye los trastornos cardiovasculares asociados con la obesidad en humanos. Rimonabant también es efectivo en la dependencia al cigarrillo y posee un perfil toxicológico relativamente seguro. Esta revisión considerara los principales efectos obtenidos con rimonabant haciendo especial énfasis en sus aplicaciones más promisorias.

Rimonabant (SR141716, Acomplia®) has been described as an antagonist/inverse agonist at the cannabinoid receptor type 1 (CB1). It has been widely used as a tool to evaluate the mechanisms by which cannabinoid agonists produce their pharmacological effects and to elucidate the respective physiological or pathophysiological roles of the CB1 receptor. In addition of being a CB1 antagonist, it has become increasingly clear that rimonabant can exert its own intrinsic actions. These may be viewed as evidence of either the inverse agonist nature of rimonabant or of tonic activity of the endocannabinoid system that tends to change according to the circumstances. Amongst the several effects of rimonabant, the most clinically relevant are its anti obesity properties and its ability to attenuate nicotine dependence. To date, data obtained from clinical trials (RIO North America, RIO Europe and RIO Lipid) indicate that rimonabant may have major clinical benefits in relation to its anti-obesity properties and as a novel candidate for the treatment of metabolic and cardiovascular disorders associated with overweight and obesity. Other clinical trials, such as the STRATUS study, have also shown that rimonabant may be effective in smoking cessation, and that the drug has a reasonable safety profile. This review will focus on the main effect obtained to date with rimonabant.