On-line application

XRF nowadays provides accurate concentration data at major and low trace levels for nearly all the elements in a wide variety of materials. Hardware and software advances enable on-line application of the fundamental approach in either classical or influence coefficient algorithms for the correction of absorption and enhancement effects. Vendors software packages, such as QuantAS (ARL), SSQ (Siemens), X40, IQ+ and SuperQ (Philips), are precalibrated analytical programs, allowing semiquantitative to quantitative analysis for elements in any type of (unknown) material measured on a specific X-ray spectrometer without standards or specific calibrations. The basis is the fundamental parameter method for calculation of correction coefficients for matrix elements (inter-element influences) from fundamental physical values such as absorption and secondary fluorescence. UniQuant (ODS) calibrates instrumental sensitivity factors (k values) for 79 elements with a set of standards of the pure element. In this approach to inter-element effects, it is not necessary to determine a calibration curve for each element in a matrix. Calibration of k values with pure standards may still lead to systematic errors for unknown polymer samples. UniQuant provides semiquantitative XRF analysis [242]. 

Clearly, the potential applications for vibrational spectroscopy techniques in the pharmaceutical sciences are broad, particularly with the advent of Fourier transform instrumentation at competitive prices. Numerous sampling accessories are currently available for IR and Raman analysis of virtually any type of sample. In addition, new sampling devices are rapidly being developed for at-line and on-line applications. In conjunction with the numerous other physical analytical techniques presented within this volume, the physical characterization of a pharmaceutical solid is not complete without vibrational analysis. 

Several case studies will be discussed in this chapter to show the use of and possible implementation methods for the ideas discussed in the previous chapters in a practical environment. The examples of application consist of two industrial cases for which real plant data were available, and an on-line application for the monitoring and control of a distillation column through a distributed control system. 

The SQUID obviously has several potential advantages for on-line applications. It can operate at very low inhomogeneous magnetic fields, avoiding the need for large expensive shimmed magnets. It also does not require tuning and has very low power requirements. However there are also severe technical limitations to be overcome before it can be used in on-line commercial operations. The whole SQUID needs to be immersed in liquid helium and a conventional RF coil is still needed to excite the NMR resonance. It remains to be seen whether such devices will find future on-line application in horticulture. 

Transfer optics The interface of the IR beam with the sample, especially in a classified hazardous environment, can be a major challenge. Gas samples are not too difficult although it is important to pay attention to the corrosivity of the gases, relative to the windows and any internal optics, as with a folded path length cell. Liquids offer different challenges. For on-line applications users prefer to minimize the use of valves, bypass streams and auxiliary pumps, especially over long distances between the stream and the analyzer. At times there is a benefit to sample the stream either directly or as close as possible... 

A true on-line application of NMR that is widely used in the held and based on this unilateral NMR technology is downhole NMR sensing performed by the gas and oil exploration and production companies such as Schlumberger, Halliburton, Baker Hughes, and Chevron. These tools are typically provided as a... 

TD-NMR sampling is decidedly more difficult than HR-NMR because on-line applications of low-resolution NMR have tended to focus on solid materials such as tablets, polymers, toothpaste, cellulose, foodstuffs. 

As stated previously, the focus of this review is the truly on-line application of NMR in an industrial manufacturing facility. There are many papers in the literature describing chemometric applications of laboratory NMR data to produce chemometric relationships between NMR data and physical/chemical properties These applications will not be discussed in detail here but are noteworthy as the approaches described can... 

NIR methods are not the only on-line applications for blend monitoring FT-Raman " and laser induced fluorescence (LIF) have been utilized. Refer to Chapter 11 for a comprehensive review of LIF. As stated herein, NIRS is well established as an effective and advantageous means to deem blend homogeneity and blending end point, however there are circumstances in which NIR is insufficient. For example, LIF can be more suitable for blends with low drug load. Lai and Cooney illustrated in a lab-scale experiment that LIE yielded a limit of detection below 0.02% w/w for a given API. ... 

For use in a strategy such as SHMPC, a model must also be relatively small because it must provide real-time output in an on-line application. In a batch process, such as autoclave curing, model output must be available before the process moves into its next phase (i.e., before the next measurement is recorded). This requirement for real-time models in an on-line application limits the types of models that can serve in SHMPC. 

Some instruments are available for process on-line application (Table 6.7). Capillary types give good results with Newtonian fluids and are based upon Poiseuille s law (Volume 1, equation 3.30). The pressure drop across the capillary... 

The precision of isotope ratio measurement in on-line applications is rather low as mainly caused by the high noise level of sequential ICP-MS instruments and a time dependent isotope ratio shift caused by the time depending elution signal of IC and the different times at which the masses for isotope ratio determinations are measured [ 24 ]. 

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