Batch techniques data analysis

Advantages and Disadvantages 41 Specific Batch Techniques 42 Data Analysis 46 Flow and Stirred-Flow Methods 46 Advantages and Disadvantages 46 Continuous Flow Method 48 Fluidized Bed Reactors 50 Stirred-Flow Technique 51... 

Laboratory QC data are classified as batch QC data and individual sample QC data. For all types of analysis, batch QC data originate from laboratory blanks, laboratory control samples, matrix spikes, and laboratory duplicates. Individual sample QC data in organic compound analysis are obtained from surrogate and internal standard recoveries. Matrix interference detection techniques (serial dilution tests, postdigestion spike additions, and MSA tests) are the source for individual sample QC checks in trace element analysis. (Chapter 4.4.4.5 addresses the trace element matrix interference detection techniques and the associated acceptance criteria.)... 

It appears that the gas-purge and miscible-displacement techniques yield comparable results. In addition, the miscible-displacement technique has been shown to yield results similar to those of batch-rate studies when similar time scales are used (Brusseau et al., 1991c). This would suggest that the three methods are measuring the same physicochemical process. This also suggests that the bicontinuum model, since it was used successfully in data analysis... 

Several experimental techniques and data analysis methods can be employed to study the nucleation/growth kinetics and CSD in batch crystallizers. 

Experimental details of the batch method used to determine binary adsorption isotherms were previously described [16]. In the batch technique, a known amount of mixture of the component(s), eventually in a solvent are contacted with adsorbent and from an analysis of the external phase after equilibration and a mass balance, the amount adsorbed is calculated. In a two conponent mixture, one is limited to low concentrations of the adsorbates, as the amount of adsorbate added to the zeolite can not largely exceed the available micropore volume, in order to be able to accurately detect changes in the concennation upon adsorption. Data are at room temperature (20°C) unless otherwise noted. 

Since the reliability of gas turbines in the power industry has been lower than desired in recent years because of hot-corrosion problems, techniques have been developed to detect and control the parameters that cause these problems. By monitoring the water content and corrosive contaminant in the fuel line, any changes in fuel quality can be noted and corrective measures initiated. The concept here is that Na contaminants in the fuel are caused from external sources such as seawater thus, by monitoring water content, Na content is automatically being monitored. This on-line technique is adequate for lighter distillate fuels. For heavier fuels, a more complete analysis of the fuel should be carried out at least once a month using the batch-type system. The data should be input directly to the computer. The water and corrosion detecting systems also operate in conjunction with the batch analysis for the heavier fuels. 

Initial Situation An experimental granulation technique is to be evaluated a sample of tablets of the hrst trial run is sent to the analytical laboratory for the standard batch analysis prescribed for this kind of product, including content uniformity (homogeneity of the drug substance on a tablet-to-tablet basis, see USP Section (905)" ), tablet dissolution, friability (abrassion resistance), hardness, and weight. The last two tests require little time and were therefore done first. (Note Hardness data is either given in [kg-force] or [N], with 1 kg = 9.81 Newton). 

A technique is described [228] for solving a set of dynamic material/energy balances every few seconds in real time through the use of a minicomputer. This dynamic thermal analysis technique is particular useful in batch and semi-batch operations. The extent of the chemical reaction is monitored along with the measurement of heat transfer data versus time, which can be particularly useful in reactions such as polymerizations, where there is a significant change in viscosity of the reaction mixture with time. 

Chromatographic techniques represent one of the most significant sources of analytical data found in today s pharmaceutical laboratories. All of the chromatographic techniques produce data that must be acquired, interpreted, quantified, compared, reported, and finally archived (see Chapter 21). Whether the analysis is qualitative or quantitative in nature, the data must somehow be interpreted and reported so that meaningful decisions can be made. It may be as simple as a qualitative decision that indicates whether a reaction has reached completion successfully, or it may be a series of quantitative analyses that help determine if a batch or lot of product meets its specifications and may now be released. This chapter also examines the evolution and perhaps the revolution that has taken place within the chromatography data system (CDS) marketplace. 

Tavare and Garside ( ) developed a method to employ the time evolution of the CSD in a seeded isothermal batch crystallizer to estimate both growth and nucleation kinetics. In this method, a distinction is made between the seed (S) crystals and those which have nucleated (N crystals). The moment transformation of the population balance model is used to represent the N crystals. A supersaturation balance is written in terms of both the N and S crystals. Experimental size distribution data is used along with a parameter estimation technique to obtain the kinetic constants. The parameter estimation involves a Laplace transform of the experimentally determined size distribution data followed a linear least square analysis. Depending on the form of the nucleation equation employed four, six or eight parameters will be estimated. A nonlinear method of parameter estimation employing desupersaturation curve data has been developed by Witkowki et al (S5). 

Unfortunately, the publication by Williams and coworkers is one of the only reports of a scale-up problem involving liquids or semisolids in the pharmaceutical literature. A number of papers that purport to deal with scale-up issues and even go so far as to compare the properties of small versus large batches failed to apply techniques, such as dimensional analysis, that could have provided the basis for a far more substantial assessment or analysis of the scale-up problem for their system. Worse yet, there is no indication of how scale-up was achieved or what scale-up algorithm(s), if any, were used. Consequently, their usefulness, from a pedagogical point of view, is minimal. In the end, effective scale-up requires the complete characterization of the materials and processes involved and a critical evaluation of all laboratory and production data that may have some bearing on the scalability of the process. 

Another case for concurrent validation is that effort that requires statistical (and possibly trend) analysis. It is appropriate to digress and explain what is meant by trend analysis. This activity really consists of product auditing, which is described in more detail elsewhere [32], Product auditing is a QA (management) technique in which each batch s analytical data provide a running score-board of product performance. The quality standards would be measured periodically (monthly, quarterly, or semiannually), which would depend entirely on the number of batches made per time interval. At least six batches would be made in the same manner per chosen time interval. The data would be measured, and then it would be determined (through charting the data) if the data fell between predetermined specification limits. Each new period s data would be... 

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