Pharmacokinetics of a 503B outsourcing facility-produced theophylline in dogs

Theophylline is an important drug for treatment of canine chronic bronchitis and bradyarrhythmias, but new products require validation since pharmacokinetics in dogs can vary by formulation. A new, 503B outsourcing facility-produced theophylline product (OFT) is available for veterinary use. Outsourcing facilities have many advantages over traditional compounding sources including current good manufacturing practice compliance. The purpose of this study was to establish the pharmacokinetics of OFT in dogs. Eight healthy dogs received 11 mg/kg intravenous aminophylline and 10 mg/kg oral OFT followed by serial blood sampling in a two-way, randomized, crossover design with 7-day washout. Plasma theophylline concentrations were quantified by liquid chromatography-mass spectrometry. Bioavailability, maximum concentration, time to maximum concentration, half-life and area under the curve were: 97 ± 10%, 7.13 ± 0.71 μg/mL, 10.50 ± 2.07 h, 9.20 ± 2.87 h, and 141 ± 37.6 μg*h/mL, respectively. Steady-state predictions supported twice daily dosing of the OFT, but specific dosage recommendations are hindered by lack of a canine-specific therapeutic range for plasma theophylline concentration. These findings suggest that the OFT is well absorbed and can likely be dosed twice daily in dogs, but future pharmacodynamic and clinical studies are needed to establish a definitive therapeutic range for theophylline in this species.

A Study of Formation of Circulation Patterns in Laminar Unsteady Lid-Driven Cavity Flows Using PIV Measurement Techniques

An experimental study was conducted to observe/visualize, the formation of circulation patterns inside a square cavity due to the movement of a lid at constant velocity. Lid driven cavity flow is one of the benchmark studies used in the verification/improvement of CFD codes for internal flow applications/predictions. Previous work on this topic is primarily focused on improving the steady state predictions of the CFD codes using different numerical schemes and algorithms. Furthermore, almost all of the studies reported in computational fluid mechanics literature relates to steady state predictions of lid or shear driven flows. Experimental work that is reported in these studies is limited in scope and number. This paper reports on the measurements we made using Particle Image Velocimeter (PIV) technique to determine the flow field as it develops from stagnation to steady state inside a square cavity driven by a lid. For this purpose, we employed a 2-D PIV system, which uses a double-cavity, Nd:Yag laser to illuminate the test cavity. Experiments were conducted using water as the working fluid inside a square cavity that is one inch (25.4 mm) high and one inch wide. The depth of the cavity is five inches (127 mm) to ensure two-dimensional circulations patterns. Hollow glass sphere particles with 10 microns in diameter were used as seeding of the working fluid, water. Experiments were repeated for different lid velocities corresponding to lid Reynolds numbers (laminar to beginning of transition of turbulence.) Velocity fields were captured during the development of the circulations patters each being unique for the time of the measurement and value of the lid velocity. The center of the circulation pattern and its path inside the cavity is constructed from the captured images as steady state is attained. Also, the strength of the circulation (as manifested by the increase in the diameter of the circulation) is determined at different times for different Reynolds numbers.

Modeling Approach and Predictions of Boron Mixing in Core Bypass of ESBWR

Computational fluid dynamics (CFD) is used to predict the mixing and transport of a Boric acid solution in the core bypass region of the General Electric (GEH) Economic Simplified Boiling Water Reactor (ESBWR) during an anticipated transient without scram (ATWS) scenario. Transient boundary conditions are synthesized from a set of system code predictions. Full-scale CFD predictions are completed using a representative geometry. Symmetry is used to reduce the domain to 1/8th of the core bypass. Forty-five million finite volume cells are used to define the computational domain inside the core barrel which is made up of the small passages between the fuel channels and an outer peripheral open space. The size of the model posed special challenges in the FLUENT CFD model development and execution. The solution required a large number of iterations with reduced solver under-relaxation factors to ensure stable convergence. Steady-state predictions were completed to quantify the sensitivity of the results to variations in selected boundary conditions. These results show good transport of the Boron into the inner regions of the core bypass with no significant sensitivity of the result to changes in the distribution of flow from the top surface. The results also showed no significant impact to changing the specific gravity of the incoming jets from 1.05 to 1.0. Only a significant change in the leakage rate from the bypass and/or a change in the mass flow rate of injected Boron solution were able to impact the distribution and quantity of the Boron in the core. These results are in line with expectations. The predictions indicate efficient penetration of the Boron into the interior regions of the core bypass during an ATWS.

Simulation and Analysis of Fluid Dynamic Behaviour of Foods during Filling Processes

This research presents a model describing the behaviour of a non-Newtonian shear-thinning fluid during aseptic filling processes, in order to determine the influence of the behaviour of fluids on the performance of filling valves in aseptic beverage plants, mainly in terms of the time required to perform the filling process. The ultimate aim of the study is to explore the possibility of improving the accuracy of industrial filling processes, so as to be able to utilise them with high viscosity fluids.The numerical model, exploiting the Finite Elements Method (FEM), was designed using the commercial software Comsol Multiphysics, and validated by comparing the steady state predictions with outcomes of filling experiments performed in industrial laboratories. Hence, subsequent numerical simulations were performed to investigate the transition from laminar to turbulent flow for shear-thinning fluids under different pressure conditions, in 3D time-dependent configurations. Results of the simulations, performed on a low fat yoghurt, show that laminar flow subsists within the whole filling system when the Metzner-Reed Reynolds number at the inlet section of the valve is lower than approx 444.

Transient Analysis of Tyre Friction Generation Using a Brush Model with Interconnected Viscoelastic Bristles

An analysis of the mechanism of tyre contact force generation under transient conditions is presented. For this purpose, two different versions of a brush model are used, both with inertial and viscoelastic properties. The first model consists of independent bristles, while the second, with a more realistic scenario, introduces viscoelastic circumferential connections between the sequential bristles, which affect the lateral degrees of freedom. Friction between the tyre and the ground follows an experimentally verified stick-slip law. For the model with independent bristles, the state of each bristle at any instant of time depends only on the state of the same bristle at a previous time step. In the second model, the instantaneous state depends on the state of the same bristle at the preceding time step, as well as on the state of the two adjacent bristles at the same time. Simulation results reveal the differences between the two models and most importantly show how transient friction force generation may differ substantially from steady state predictions. The findings suggest that transient tyre behaviour should not be attributed solely to the contributions of the flexible belt and carcass. On the contrary, the observed transience in the neighbourhood of the contact patch should also be taken into account.

Virus Transmission Through Compromised Synthetic Barriers: Part I—Effect of Unsteady Driving Pressures

Although synthetic membranes such as gloves, condoms, and instrument sheaths are used in environments with highly time-varying stresses, their effectiveness as barriers to virus transmission is almost always tested under static conditions. In this paper it is shown how a previously developed mathematical model can be used to transform information from static barrier tests into predictions for more realistic use conditions. Using a rate constant measured for herpes adsorption to latex in saline, and an oscillatory trans-membrane pressure representative of coitus, the amount of virus transmitted through a hole (2 μm diameter) in a condom is computed. Just beyond the exit orifice of the pore, transport is dominated by the rapidly dissipating viscous jet of virus suspension, which results in an accumulation of viruses roughly 20 pore radii from the barrier surface during each cycle. Due to virus adsorption to the barrier surfaces, the simulations reveal a gradual decrease in virus flow with increasing number of cycles, and thus a slow divergence from predictions based upon steady-state conditions. Still, over the 500 cycles simulated, steady-state predictions approximate the net number of viruses transmitted to within 25 percent error.

Analysis of an Accelerating Rotor-Bearing System With Flexible Damped Supports

This paper deals with the dynamics of an accelerating unbalanced Jeffcott rotor-bearing system mounted on damped, flexible supports. The general equations of motion for such a system are presented and discussed. The rotor response was predicted, via numerical integration, for various cases in runup and rundown conditions and presented in graphical form. The effects of acceleration on the rotor peak amplitude and the speed at which the peak occurs is discussed and compared to steady state predictions.

The Minimum Film Thickness in Line Contacts During Reversal of Entrainment

In contacts, such as cams, non-involute gears and shaft seals, where the direction of entrainment reverses during the operating cycle, the minimum film thickness is typically found just after the reversal. This paper shows that this minimum film thickness is determined by the rate of change of the entraining velocity and by the fluid and surface properties. For line contacts, four regimes of lubrication are found—as for the steady-state situation—and expressions for the film thickness in each regime are developed. This enables an outline design chart for the minimum film thickness to be constructed. It is shown that this information, together with the steady-state predictions is sufficient to determine the variation of film thickness with time in most situations where load, radius of curvature, and entraining velocity vary.