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.     

Impulse breakdown voltages of triggered multistage vacuum gap

Several sealed-off triggered vacuum gaps are connected in series to improve hold-off voltage. The characteristics of impulse breakdown voltage of these series-connected gaps are investigated experimentally. The sum hold-off voltage of series-connected gaps decreases to a unit hold-off voltage when the maximum value of voltage division ratio across the gaps increases to unity. Self-breakdown probability of the series-connected gaps is always higher than that of a single gap under the same conditions. Hence, stage efficiency of the multistage gap decreases with increasing number of stages. Its value is 90 percent with 2-stage gap and 75 percent with 5-stage gap, respectively, under the same voltage division ratio and the same gap length (2.0 mm) in each stage. Triggered breakdown voltage of 2- or 3- stage gap is several hundred volts when all gaps are triggered simultaneously at the peak of the main impulse wave and a working voltage range is nearly 100 percent in this case. The working voltage range decreases with number of stages. Its value is 45 percent with 3-stage gap and 15 percent with 5-stage gap, respectively, when one triggered gap is fired for switching.     

Thermoelastic solutions for orthotropic and anisotropic composite laminates

Solutions, within the framework of linear uncoupled thermoelasticity, are presented for certain problems of flexure of composite laminates. Benchmark numerical results, useful for the validation or otherwise of approximate laminate models, are tabulated. Finally, these results are used to examine the accuracy of the classical lamination theory based on Kirchhoff's hypothesis.     

Zooplankton population in the river tigris: Effects of samarra impoundment

The influences of the Samarra impoundment on the ecology of the downstream sector of the river Tigris are investigated. Zooplankton were collected monthly from July 1987 to July 1988. It was found that zooplankton were most abundant during high river discharges in March. During the month of low river discharge, September, the zooplankton population was greatly reduced immediately below the barrage and remained so to the last downstream station. Several factors seem to explain such differences. The high discharge from the impoundment was found to be the dominating factor and may flush the small backwaters in which zooplankton were abundant, thus increasing the population in the river. Zooplankton species vary in their ability to sustain populations in the river, variations which are due mainly to species-specific characteristics.     

Capacity planning in job-shop environment

Presented here is a computerized capacity planning system for the IBM Microcomputer family. The system maintains the profile of the job shop in a data base along with data pertinent to various products that can be manufactured in the shop. Projected orders for the planning period are input to the system with their associated quantities and delivery dates. The system uses the forward and backward loading rules in generating capacity loading scenarios. User selects the best course of action which may satisfy delivery dates subject to the limitations of the work centers. Efficiency figures are provided to aid the user in his/her decision.