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.     

Oxygenation in the rabbit myocardium: assessment with susceptibility-dependent MR imaging

PURPOSE: To determine the feasibility of using hemoglobin (Hb) desaturation as an indicator of myocardial oxygenation. MATERIALS AND METHODS: High-resolution gradient-echo nuclear magnetic resonance (MR) images of isolated, blood-perfused rabbit hearts were obtained at various blood oxygenation levels. The hearts were perfused at 37 degrees C with a Langendorff apparatus modified for nuclear MR imaging. The perfusate contained bovine red blood cells in a cardioplegic solution that eliminated motion artifacts and minimized arteriovenous oxygenation differences. Hb saturation was varied (7%-100%) randomly. Perfusion pressure was continuously monitored, and blood samples were obtained. RESULTS: There was a substantial correlation between image signal intensity in the myocardium and Hb saturation in the blood, believed to be due to susceptibility effects of the paramagnetic species deoxyhemoglobin. CONCLUSION: Direct and noninvasive determination of regional Hb saturation with susceptibility-dependent MR imaging may provide information regarding regional myocardial O2 content.     

A functional model of the electrical potential of skin

A model of the skin electrical potential has been developed. It contains electrical and functional parameters of the sweating and their dependence on efferent innervation. The analytical expression of the skin electrical potential which explains basic experimental results has been constructed.     

Vibrational analysis of functionalized polyolefins/poly(vinylchloride) blends

Polyolefins functionalized with diethylmaleate were mixed with poly(vinylchloride) (PVC) in different compositions. Intermolecular interactions involving the carbonyl groups of the side chains of the functionalized polyolefins and methine hydrogens of PVC were investigated by means of infrared spectroscopy. The major flexibility of the ester groups attached to the backbone chains, with respect to polyesters, seems to increase the capability of such groups to interact with groups of more polar polymers, thus allowing prediction of easier miscibility, which however also depends on the starting polyolefin structure and function-alization degree.     

Morphological variations of the human gastric mucosa after omeprazole treatment: a scanning electron microscopic study

The effects of antiepileptic drugs on cognitive function in 48 healthy volunteers were assessed using event-related potentials (ERP) and the Attention Index included in the Wechsler Memory Scale, revised edition (WMS-R). The study was conducted over 1 week, using a double-blind design. Four drugs, carbamazepine (CBZ), phenytoin (PHT), valproate (VPA) and zonisamide (ZNS) were tested. Using an auditory oddball task, ERP measurements were made under two conditions with different tone intensities: Condition 1 used 70 db SPL; and Condition 2 used 30 db SPL. Results showed that CBZ prolonged target N1 and P3 latencies in Condition 1, and reduced frequent N1 amplitude in Condition 2, which suggests that CBZ may cause a change in sensory memory and prolong stimulus evaluation time. It is suggested that under a low stimulus intensity level, the sensory function itself was affected. Phenytoin was found to prolong target N1 latency in Condition 2, which also indicates a change in the sensory memory function. However, VPA did not significantly affect ERP components, except for the shortened frequent N1 latency, which could not be explained due to the limited information. It was found that ZNS augmented P3 amplitude in Condition 2, and reduced scores on the Attention Index. It is suggested that the augmentation of P3 amplitude was caused by the reduction of processing negativity as a result of the detrimental effect of ZNS on subjects' attention. However, the apparent difference between the ERP and behavioral indices suggests that caution should be exercised in assessing the results obtained only from ERP measurements.     

Multi-level simulation of metal-forming processes

The IBF has for some years made use of finite element programmes to solve metal-forming problems. In the course of this investigation, it has become evident that a problem-oriented adaptation of FEM simulation to the problem in hand is beneficial in terms of computation effort. The computation time for the process parameters is optimised in a multi-level simulation. At level 1 (global analysis) integral parameters such as the required force and required work are computed using a coarse FEM mesh. At level 2 (local analysis) an optimised number of elements is used to determine continuum mechanics parameters like stress, strain and temperature. Microscopic phenomena are simulated at level 3 (microscopic analysis), using special micro-material elements and thermodynamic models.     

Necrotizing fasciitis of the face

Necrotizing fasciitis (NF) is a rapidly progressive soft tissue infection with high morbidity and mortality rates. Its occurrence in the head and neck region is uncommon, the majority of reported cases being limited to involvement of the neck, usually from infections of dental or pharyngeal origin. Involvement of the face from NF is rare; only 35 such cases have been reported in the literature since 1960. It is not only associated with a high mortality but can also result in severe disfigurement of the face, posing challenging reconstructive problems. Successful management of facial NF requires early diagnosis, prompt institution of broad spectrum antibiotics, aggressive surgical debridement to control the infection, and reconstruction of the resultant soft tissue defects. This report describes four additional cases of facial necrotizing fasciitis. One of the four patients died as a result of sepsis and multi-organ system failure. Two of the three surviving patients had significant facial disfigurement. A comprehensive review of the facial NF cases reported in the literature is also provided. Based on our experience with facial NF and the results of all previous case reports, the clinical manifestations, pathogenesis, and management of this disease are discussed.     

Gamma-Ray-Induced Multi-Effect on Properties of Chalcogenide Glasses

Gamma-ray irradiations induced various alterations in sulfur- and selenium-based chalcogenide glasses. The absorbed dose was in the range of 0.01–3.6 MGy. The glasses exhibit prominent sensitivity to γ-ray irradiation, characterized by changes in some of the physical properties of the glasses, e.g., optical transmission, optical band gap, density, and thermal expansion coefficient. The effects on glass structure and microscopic morphology were also studied by Raman spectra and scanning electron microscopic observations.     

Human gamma-interferon expression in the mammary gland of transgenic mice

Transgenic mice carrying a hybrid gene consisting of ovine beta-lactoglobulin gene sequences and human gamma-interferon (hIFN-g) cDNA were produced. hIFN-g expression in the mammary gland of two lactating transgenic founder females was found. The concentration of active hIFN-g in the milk was estimated as being ca. 1800 IU/ml. The hIFN-g ability to express in the mammary gland was found in the progeny of transgenic founder male.     

“Biaxiality Effect” on the Energy Dissipated by Elastoplastic Base-Isolators

A plane elastic-plastic solid body presenting kinematic hardening is used to simulate a pair of dampers at the base of a rigid structure and determine the energy dissipation under conditions of assigned, homogeneous cyclic loading. The well-known von Mises theory of plasticity is applied with the aim of obtaining analytical solutions to the problem. Such solutions are arrived at by first calculating the Odqvist parameter, which yields dimensionless relations that depend on the external loads and mechanical properties of the material. The results, in terms of dissipated energy, are given for the case of a sinusoidal process, represented with the help of dimensionless parameters useful for engineering applications.