Methods to compare dissolution profiles and a rationale for wide dissolution specifications for metoprolol tartrate tablets

The objectives of this work were to apply several profile comparison approaches to dissolution data of four different but bioequivalent metoprolol tartrate tablet formulations to (1) identify the advantages and disadvantages of each approach, (2) quantify the metric for comparing dissolution profiles of each method, (3) determine metric limits that are consistent with the observed bioequivalence, and (4) rationalize the observed metric limits with respect to the role of dissolution in overall metoprolol absorption. Dissolution was performed by the USP monograph method on four formulations of metoprolol tartrate tablets (Lopressor plus fast, medium, and slow dissolving test formulations). Three general approaches to compare dissolution profiles were examined; they were ANOVA-based, model-independent, and model-dependent approaches. It is concluded that model-independent approaches and several model-dependent approaches yielded numerical results that can serve as objective and quantitative metrics for comparing entire dissolution profiles of the four metoprolol tartrate formulations. However, these methods presented complications. Some metrics were dependent on the length of the dissolution profile and the sampling scheme. Results from the pairwise procedures also depended on the pairing assignment of individual profiles. In spite of complications, these methods suggested wide dissolution specification limits. Wide dissolution specifications were rationalized through an analysis of in vitro-in vivo relationships, which indicated metoprolol dissolution from these formulations was not the rate-limiting step; hence, a range of dissolution profiles can be expected to yield equivalent plasma profiles.     

Microsatellite loci for stringless bees

What ethical concerns regarding the application of new antidementia compounds are pertinent to the best interests of patients with Alzheimer's disease and their caregivers? Based on collected preliminary anecdotal accounts, these concerns are important and should be considered carefully by clinicians, researchers, and families.     

Expression of a human homeobox-containing gene is regulated by 1,25(OH)2D3 in bone cells

The seasonal variation in the nutrient composition of Enhydra fluctuans and Marsilea quadrifolia, two edible semi-aquatic plants, was studied in order to promote their consumption as green leafy vegetables. Both plants had a high crude protein content throughout all harvesting seasons. Enhydra fluctuans had a low ash content and was a good source of beta-carotene (3.7 to 4.2 mg/100 g on a fresh weight basis). Marsilea quadrifolia exhibited wide fluctuations between seasons and was not very promising in nutrient composition when compared to other commonly used green leafy vegetables.     

A microbubble-powered bioparticle actuator

We present the results of a device that uses controllable microbubble actuation to manipulate bioparticles. In order to create a useful device for controlling the position of bioparticles, predictable microfluidic actuation is crucial. The goal of this project was to develop fundamental technology that can be used to manipulate single bioparticles (e.g., cells). We use a thermal bubble actuation method to accomplish this goal. Microbubbles have the advantages of relatively simple electronics and fabrication but can be difficult to control. In this paper, we describe two specific accomplishments: the use of micromachined nucleation cavities to precisely localize thermal bubbles and to achieve controllable bubble formation temperatures and bubble dissipation and the demonstration of controllable microbubbles in a new device for particle sorting.     

Clinical applications of fundus reflection densitometry

Fundus reflection densitometry or retinal densitometry is a non-invasive technique to examine the visual photopigment kinetics in living eyes. The technique is based on the comparison of the reflected light from the fundus in a fully light adapted eye (when all visual photopigment has been bleached) with the reflected light following complete dark adaptation (when the retina contains its maximum amount of visual photopigment). The technique provides a measure of the density of visual photopigment, its time constant of regeneration, its distribution and spectral characteristics if measured at a series of wavelengths. Fundus reflection densitometry in the human eye was introduced 40 years ago. Presently, it is the only available technique from which direct and objective insight can be obtained into visual photopigment. This knowledge is particularly relevant in eyes where abnormalities of photoreceptor function are suspected. This paper summarizes the current knowledge of fundus reflection densitometry in the diseased and in the aging human retina, gathered over the last 30 years. Considerable improvements of the instrument for clinical purposes have been obtained, and are also discussed.