Process monitoring analyses examples

In several chapters we discussed how the quality of the analytical result defines the amount of information which is obtained on a sampled system. Obvious quality criteria are accuracy and precision. An equally important criterion is the analysis time. This is particularly true when dynamic systems are analyzed. For instance a relationship exists between the measurability and the sampling rate, analysis time and precision (see Chapter 20). The monitoring of environmental and chemical processes are typical examples where the management of the analysis time is... 

Most hterature references to pharmaceutical primary process monitoring are for batch processes, where a model of the process is built from calibration experiments [110, 111]. Many of these examples have led to greater understanding of the process monitored and can therefore be a precursor to design of a continuous process. For example, the acid-catalysed esterification of butan-l-ol by acetic acid was monitored through a factorial designed series of experiments in order to establish reaction kinetics, rate constants, end points, yields, equilibrium constants and the influence of initial water. Statistical analysis demonstrated that high temperatures and an excess of acetic acid were the optimal conditions [112]. 

Nonetheless, there are running plants at laboratory and pilot-scale levels at institutes/universities and industry where process control is already exerted. Usually this is done in a rather conventional fashion, e.g. using commercial pressure hold valves and temperature determination at the in- and outlets and process-specific concentration monitoring outside the micro reactor. For example, an analysis of the redox potential was used for process monitoring for continuous azo pigment production at Clariant (see Figure 4.68) [99],... 

Control charts are an excellent analysis tool to both monitor and improve in-process performance during process development and later during production, where it is desired to follow process characteristics over time within batches or runs. The most common examples of tablet process characteristics that are measured in-process are weight, thickness, and hardness. The parameters measured need to be controllable so that adjustments can be made. During the initial runs, it is desirable to limit process adjustments to a minimum to observe the process in its natural state. Any adjustments made should be recorded and explained. Out-oflimit results should never be removed prior to performing a process capability analysis. If special cause variation is detected, then process improvements should be made to eliminate the special cause variation. 

Automatic and automated instruments can be differentiated as follows automatic instruments tend to perform specific operations at given points in a process or analysis to save time or effort, e.g. robotics, while automated instruments tend to control some part of a process without human intervention and do this by means of a feedback mechanism from sensors. For example, an automatic conductivity detector might continuously monitor the conductivity of a process stream, generating some alarm if the conductivity goes outside a preset limit. An automated detection system could transmit the measured conductivity values to a control unit that, by utilising a feedback mechanism, adjusts relevant process parameters, e.g. temperature or cycle time, to maintain the conductivity of the stream within the preset limits. 

In future, multivariate analysis should be used more and more in everyday (scientific) life. Until recently, experimental work resulted in a very hmited amount of data, the analysis of which was quite easy and straightforward. Nowadays, it is common to have instmmentation producing an almost continuous flow of data. One example is process monitoring performed by measuring the values of several process variables, at a rate of one measurement every few minutes (or even seconds). Another example is quality control of a final product of a continuous process on which an FT-IR spectmm is taken every few minutes (or seconds). 

Aspects of chemistry for which automation has been a popular and effective improvement over manual processes include continuous-flow separation processes, instrumental analysis, and continuous monitoring. Radiometric measurements are a good example, as numerous samples are counted, one after the other, each for a... 

In other cases, waste minimization technologies can result in enhanced product quality. A continuous process data analysis system is one example. Rather than operator experience and intuition guiding when to cycle a process bath, computer analysis can be instituted to monitor key indicators of the process solution and automatically adjust the bath conditions. The result can be longer bath life, a more consistent product, and greater product engineer confidence (Dickinson 1995). 

Despite the problems discussed above, LIPS has been successfully applied in a number of process analysis applications. In some cases, the LIPS system has been used off-line as in the application described by Ottesen in which air cooled metallic substrates were used to collect fly ash deposits from a pulverised coal combustion for subsequent analysis off-line [70]. Calibration standards were prepared by spraying aqueous solutions onto heated substrates using an air brush and the method was found to work well provided that the deposits were sufficiently thin to permit complete ablation. Other workers have proposed on-line LIPS systems for process control. An example is the apparatus proposed by Sabsabi [71] for in situ analysis of pre-selected components of homogeneous solid compositions. In particular, the author proposed that the system could be used for measurement of the concentration of active ingredients (e.g. drugs) in pharmaceutical products such as tablets, by monitoring an element present in the active component (e.g. 

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