Dissolution profile of theophylline modified release tablets, using a biorelevant Dynamic Colon Model (DCM)

AbstractThe human proximal colon has been considered a favourable site to deliver drugs for local and systemic treatments. However, modified dosage forms face a complex and dynamically changing colonic environment. Therefore, it has been realized that in addition to the use of biorelevant media, the hydrodynamics also need to be reproduced to create a powerful in vitro dissolution model to enable in vivo performance of the dosage forms to be predicted.A novel biorelevant Dynamic Colon Model (DCM) has been developed which provides a realistic environment in terms of the architecture of the smooth muscle, the physical pressures and the motility patterns occurring in the proximal human colon. Measurements of pressure inside the DCM tube confirmed a direct association between the magnitude of the pressure signal with the occlusion rate of the membrane and the viscosity of the fluid.The dissolution profile and the distribution of the highly soluble drug, theophylline, were assessed by collecting samples at different locations along the DCM tube. Differences in the release rates of the drug were observed which were affected by the sampling point location, the viscosity of the fluid and the mixing within the DCM tube. Images of the overall convective motion of the fluid inside the DCM tube obtained using Positron Emission Tomography enabled relation of the distribution of the tracer to likely areas of high and low concentrations of the theophylline drug.This information provides improved understanding of how extensive phenomena such as supersaturation and precipitation of the drug may be during the passage of the dosage form through the proximal colon

Anastomotic loop between common hepatic artery and gastroduodenal artery in coexistence with an aberrant right hepatic artery

Anatomical variations of the hepatic arteries are not uncommon. The anomalous hepatic arterial supply is of paramount importance in hepatobiliary, pancreatic or liver transplantation and in laparoscopic surgery. We describe an unusual case of a 66-year-old Greek male cadaver, where a rare anastomosis (in the form of an enlarged arterial loop, 4.84 mm in diameter) between the common hepatic artery (6.42 mm) and the gastroduodenal artery (GDA) (4.82 mm) coexisted with an aberrant right hepatic artery (ARHA) (6.38 mm) originating from the superior mesenteric artery. The proper hepatic artery was absent. The ARHA followed a route posterior to the portal vein and the common hepatic duct, entering the liver and supplying the right hepatic segment. A hypoplastic right gastric artery emanated from the GDA. Our case report highlights the combined variations of hepatic arteries and possible anastomoses emphasizing that a thorough knowledge of the classic and variable hepatic arterial anatomy are mandatory for surgeons and radiologists performing hepatic surgery and arteriography to avoid potential iatrogenic injuries in hepatobiliary and pancreas area and further medico-legal implications

Modelling and simulation of the hydrodynamics and mixing profiles in the human proximal colon using Discrete Multiphysics

The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model). The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations

Improvement of Dynamic Soil Properties Induced by Preloading Verified by a Field Test and Embankment Failure

The results of an elaborate field preloading study on a liquefaction-susceptible site are presented. Preloading was applied by a temporary embankment 9m high. Prior and after preloading, borings with standard penetration tests, cone penetration tests and geophysical studies were performed. During the process of embankment construction and demolition, settlements, excess pore pressures and vertical and horizontal stresses were recorded versus time at different locations. A partial embankment failure occurred during the preloading process. A method predicting failure during the construction of the preload embankment based on excess pore pressure measurements is proposed and verified

Emergence of Oscillons in an Expanding Background

We consider a (1+1) dimensional scalar field theory that supports oscillons, which are localized, oscillatory, stable solutions to nonlinear equations of motion. We study this theory in an expanding background and show that oscillons now lose energy, but at a rate that is exponentially small when the expansion rate is slow. We also show numerically that a universe that starts with (almost) thermal initial conditions will cool to a final state where a significant fraction of the energy of the universe -- on the order of 50% -- is stored in oscillons. If this phenomenon persists in realistic models, oscillons may have cosmological consequences.Comment: 13 pages, 4 .eps figures, uses RevTeX4; v2: clarified details of expansion, added reference

Publisher correction : The duality between particle methods and artificial neural networks

This Article contains a typographical error in the Code availability section. "The code used for the simulations is freely available under the GNU General Public License v3 and can be downloaded from the Cranfield repository https ://publi c.cranf​ield.ac.uk/e1020 81/DeepM P/." should read: "The code used for the simulations is freely available under the GNU General Public License v3 and can be downloaded from the Cranfield repository http://publi c.cranf​ield.ac.uk/e1020 81/DeepM P/.