Relationship between diffusivity of water molecules inside hydrating tablets and their drug release behavior elucidated by magnetic resonance imaging

We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.     

Novel method for constructing a large-scale design space in lubrication process by using bayesian estimation based on the reliability of a scale-up rule

A reliable large-scale design space was constructed by integrating the reliability of a scale-up rule into the Bayesian estimation without enforcing a large-scale design of experiments (DoE). A small-scale DoE was conducted using various Froude numbers (X(1)) and blending times (X(2)) in the lubricant blending process for theophylline tablets. The response surfaces, design space, and their reliability of the compression rate of the powder mixture (Y(1)), tablet hardness (Y(2)), and dissolution rate (Y(3)) on a small scale were calculated using multivariate spline interpolation, a bootstrap resampling technique, and self-organizing map clustering. A constant Froude number was applied as a scale-up rule. Experiments were conducted at four different small scales with the same Froude number and blending time in order to determine the discrepancies in the response variables between the scales so as to indicate the reliability of the scale-up rule. Three experiments under an optimal condition and two experiments under other conditions were performed on a large scale. The response surfaces on the small scale were corrected to those on the large scale by Bayesian estimation using the large-scale results and the reliability of the scale-up rule. Large-scale experiments performed under three additional sets of conditions showed that the corrected design space was more reliable than the small-scale design space even when there was some discrepancy in the pharmaceutical quality between the manufacturing scales. This approach is useful for setting up a design space in pharmaceutical development when a DoE cannot be performed at a commercial large manufacturing scale.     

Accurate position detection of targets in noise image

Targets at various positions in a noise image were detected by the optical matched filtering technique. In this case the thermoplastic optical recorder was used as a matched filter recorder. High accuracy of position detection was obtained, i.e. the position error was 2% or less.     

Observation of rat hind limb skeletal muscle during arterial occlusion and reperfusion by 31P MRS and 1H MRI

31P NMR spectra and 1H MR T1- and T2-weighted spin-echo images were concurrently observed in rat hind limb during arterial occlusion and following reperfusion. With arterial occlusion, phosphocreatine level decreased and inorganic phosphate (Pi) level increased in 31P NMR spectra. Intracellular pH's dropped as a function of time. Beta-ATP started to decrease in three hours. In six hours after the occlusion, any peaks other than Pi were scarcely detected. The signal intensities in the 1H MR images increased homogeneously in both T1- and T2-weighted conditions, but the changes were more profound with T2-weighted images. After the release of the arterial occlusion, the 31P NMR spectra recovered to the preischemic state in several hours. The 1H MR images during reperfusion showed characteristic heterogenous pattern. The signal intensities in the anterior tibial muscle and the gastrocnemius muscle remained high in T1-weighted condition and the intensities further increased in T2-weighted condition, while those in other parts returned to the preischemic level. These changes were found to be irreversible even 12 hr after the release. The high signal intensities suggested the increase of water in the extracellular compartment induced by so-called reperfusion injury. Multinuclear analysis using in vivo NMR was valuable to consecutively detect time-dependent and location-specific response in skeletal muscle during ischemia and reperfusion.     

Infrared seed inspection system (IRSIS) on painted car shells

This paper describes a newly-developed automated thermal system for detection of seeds on newly painted car shells. The system’s novel approach is to use thermal emission; previously applied techniques relied on light reflection strategies. The system is described beginning with analytical modeling of the underlying detection theory to verification on a pilot run in an automotive production line. Parker’s flash procedure, using a thermal detector, was performed to extract the thermal properties of inspected panels. New computer logic developed in-house for processing the acquired thermograms is also presented.     

Synthesis and electroluminescence properties of fluorene containing arylamine oligomer

We synthesized a blue fluorescent fluorene containing arylamine oligomer, bis(9,9,9′,9′‐tetra‐n‐octyl‐2,2′‐difluorenyl‐7‐yl)phenylamine (DFPA), and investigated its electroluminescence (EL) properties. Organic EL devices with a structure of glass/indium‐tin oxide/acid‐doped poly(thiophene) derivative/DFPA/aluminum complex (BAlq)/cesium‐doped macrocyclic compound/Al were fabricated. The device exhibited blue emission, peaking at 432 nm, from the DFPA layer. The maximum luminance of 1800 cd/m² and an external quantum efficiency of 1.5% were observed. Copyright © 2004 John Wiley & Sons, Ltd.     

The first x-ray structure determination of a -phosphaethylene: -2-phenyl-1-(2,4,6-tri-t-butylphenyl)phosphaethylene

The sterically protected -phosphaethylene, -2-phenyl-1-(2,4,6-tri-t-butylphenyl)phosphaethylene (1-Z), was analyzed by X-ray crystallography.