MRI pressure and stress measurement in novel homogeneous soft solids

This paper presents MRI measurements of a novel semi solid MR contrast agent to pressure. The agent is comprised of potassium chloride cross linked carageenan gum at a concentration of 2% w/v, with micron size lipid coated bubbles of air at a concentration of 3% v/v. The choice for an optimum suspending medium, the methods of production and the preliminary MRI results are presented herein. The carageenan gum is shown to be ideally elastic for compressions relating to volume changes less than 15%, in contrast to the inelastic gellan gum also tested. Although slightly lower than that of gellan gum, carageenan has a water diffusion coefficient of 1.72×10-9 m2.s-1 indicating its suitability to this purpose. RARE imaging is performed whilst simultaneously compressing test and control samples and a maximum sensitivity of 1.6% MR signal change per % volume change is found which is shown to be independent of proton density variations due to the presence of microbubbles and compression. This contrast agent could prove useful for numerous applications, and particularly in chemical engineering. More generally the method allows the user to non-invasively image with MRI any process that causes, within the solid, local changes either in bubble size or bubble shape. © 2008 American Institute of Physics.

Paediatric drug development of ramipril:reformulation, in vitro and in vivo evaluation

Ramipril is used mainly for the treatment of hypertension and to reduce incidence of fatality following heart attacks in patients who develop indications of congestive heart failure. In the paediatric population it is used most commonly for the treatment of heart failure, hypertension in type 1 diabetes and diabetic nephropathy. Due to the lack of a suitable liquid formulation, the current study evaluates the development of a range of oral liquid formulations of ramipril along with their in vitro and in vivo absorption studies. Three different formulation development approaches were studied: solubilisation using acetic acid as a co-solvent, complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) and suspension development using xanthan gum. Systematic optimisation of formulation parameters for the different strategies resulted in the development of products stable for twelve months at long term stability conditions. In vivo evaluation showed CMAX of 10.48 µg/mL for co-solvent, 13.04µg/ml for the suspension and 29.58µg/mL for the cyclodextrin based ramipril solution. Interestingly, both ramipril solution (co-solvent) and the suspension showed a TMAX of 2.5h, however, cyclodextrin based ramipril produced TMAX at 0.75h following administration. The results presented in this study provide translatable products for oral liquid ramipril which offer preferential paediatric use over existing alternatives.

Uncertainty evaluation of an axi-symmetric measurement machine

This paper describes a method of uncertainty evaluation for axi-symmetric measurement machines which is compliant with GUM and PUMA methodologies. Specialized measuring machines for the inspection of axisymmetric components enable the measurement of properties such as roundness (radial runout), axial runout and coning. These machines typically consist of a rotary table and a number of contact measurement probes located on slideways. Sources of uncertainty include the probe calibration process, probe repeatability, probe alignment, geometric errors in the rotary table, the dimensional stability of the structure holding the probes and form errors in the reference hemisphere which is used to calibrate the system. The generic method is described and an evaluation of an industrial machine is described as a worked example. Type A uncertainties were obtained from a repeatability study of the probe calibration process, a repeatability study of the actual measurement process, a system stability test and an elastic deformation test. Type B uncertainties were obtained from calibration certificates and estimates. Expanded uncertainties, at 95% confidence, were then calculated for the measurement of; radial runout (1.2 µm with a plunger probe or 1.7 µm with a lever probe); axial runout (1.2 µm with a plunger probe or 1.5 µm with a lever probe); and coning/swash (0.44 arc seconds with a plunger probe or 0.60 arc seconds with a lever probe).