Novel platens to measure the hardness of a pentagonal shaped tablet.

Tablet hardness, a measure of the breaking force of a tablet, is based on numerous factors. These include the shape of the tablet and the mode of the application of force. For instance, when a pentagonal-shaped tablet was tested with a traditional hardness tester with flat platens, there was a large variation in hardness measurements. This was due to the propensity of vertices of the tablet to crush, referred to as an "improper break". This article describes a novel approach to measure the hardness of pentagonal-shaped tablets using modified platens. The modified platens have more uniform loading than flat platens. This is because they reduce loading on the vertex of the pentagon and apply forces on tablet edges to generate reproducible tablet fracture. The robustness of modified platens was assessed using a series of studies, which included feasibility and Gauge Repeatability & Reproducibility (R&R) studies. A key finding was that improper breaks, generated frequently with a traditional hardness tester using flat platens, were eliminated. The Gauge R&R study revealed that the tablets tested with novel platens generated consistent values in hardness measurements, independent of batch, hardness level, and day of testing, operator and tablet dosage strength.

Experimental and model-based approaches to studying mixing in coating pans.

The focus of this study was the determination of mixing patterns and rates inside a cylindrical coating pan. The research for this study was divided into two parts. The first part examined the mixing pattern and the movement of tablets inside of a coating pan experimentally. The second part consisted of using a DEM (Discrete Element Model) simulation to evaluate mixing in the coating pan in silico. Mixing was investigated as a function of the rate of rotation of the pan and the number of revolutions. Mixing rates were measured in two directions--axial--from the front of the unit to the back of the unit along its axis and radial/angular--in the plane orthogonal to its axis. Radial/angular mixing was faster than axial mixing--the coating pan was found to be well-mixed across the axis within 2-8 revolutions as compared to 16-32 revolutions needed for the pan to be well-mixed along the axis. The DEM simulation used for this study is capable of predicting how fast the tablets mix in the coating pan. It does so by explicitly modeling the motion of individual tablets in the unit. Model predictions were verified by comparing the simulated mixing in the coating pan to the experiments. The simulated mixing process is found to be slightly slower than the experimentally observed mixing, which means that the simulations give a conservative estimate of mixing rates. The model can also be used to calculate the residence time distribution of the tablets in a spray zone of a given area.

Down-modulation of TCR expression by Salmonella enterica serovar Typhimurium.

T cell-mediated adaptive immunity is required to help clear infection with the facultative intracellular bacterial pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), yet development of T cell-mediated adaptive immunity to S. Typhimurium has been described as slow and inefficient. A key step in inducing T cell-mediated adaptive immunity is T cell priming; the activation, proliferation, and differentiation of naive T cells following initial encounter with Ag. We previously demonstrated that S. Typhimurium had a direct inhibitory effect on naive T cells from mouse, blocking their proliferation. In this study, we show that S. Typhimurium down-modulates expression of the TCR beta-chain, a molecule that is essential for Ag recognition and T cell function. Specifically, we demonstrate that reduced amounts of surface and intracellular TCR-beta protein and decreased levels of tcrbeta transcript are expressed by T cells cultured in the presence of S. Typhimurium. We further show that the down-modulation of TCR-beta expression requires contact between S. Typhimurium and the T cells and that once contact occurs, a factor capable of reducing TCR-beta expression is secreted. These results provide new insight into the mechanism by which S. Typhimurium may inhibit T cell priming and avoid clearance by the adaptive immune system.