Pharmaceutical systems identification

X-ray powder diffractometry is a relatively straightforward technique for phase identification. There are, however, numerous sources of error in quantitative XPD. The issues that are of greatest relevance to pharmaceutical systems are enumerated in the following. 

The use of a cooling accessory permits XRD patterns to be obtained under subambient conditions. In pharmaceutical systems, the greatest utility of the technique is to monitor the crystallization of solutes in frozen solutions. Conventionally, differential scanning calorimetry has been the most popular technique for the characterization of frozen systems. However, as mentioned earlier, this technique has some drawbacks (i) It does not enable direct identification of crystalline solid phase(s). Moreover, it is difficult to draw any definitive conclusions about the degree of crystallinity, (ii) The interpretation of DSC curves is very difficult if there are overlapping thermal events. Low temperature XRD was found to be an excellent complement to differential thermal analysis in the characterization of water-glycine-sucrose ternary systems. " ... 

Prior to the much-vaunted renaissance of the Raman technique with the advent of FT instrumentation or the availability of CCD systems, there were few literature reports on the use of Raman spectroscopy for investigating pharmaceutical systems. The technique has been used to characterize drugs in much the same way that infrared has been used for identification testing. Thus, the infrared (IR) and Raman spectra of Dapsone, used in the treatment of leprosy, have been reported [1]. 

Examples of nir analysis are polymer identification (126,127), pharmaceutical manufacturing (128), gasoline analysis (129,130), and on-line refinery process chemistry (131). Nir fiber optics have been used as immersion probes for monitoring pollutants in drainage waters by attenuated total internal reflectance (132). The usefulness of nir for aqueous systems has led to important biological and medical appHcations (133). 

Pharmaceutical packaging is the means of providing protection, presentation, identification and information, containment, and convenience to encourage compliance with a course of therapy. The period from product manufacture to ultimate use or administration lies within the product shelf life interval. Criteria for selecting a satisfactory packaging system for pharmaceutical products are established by addressing a checklist of basic considerations ... 

The identification and characterization of cell culture systems (e.g., Caco-2-cells) that mimic in vivo biological barriers (e.g., intestinal mucosa) have afforded pharmaceutical scientists the opportunity to rapidly and efficiently assess the permeability of drugs through these barriers in vitro. The results generated from these types of in vitro studies are generally expressed as effective permeability coefficients (Pe). If Pe is properly corrected to account for the barrier effects of the filter (PF) and the aqueous boundary layer (PAbl) as previously described in Section II.C, the results provide the permeability coefficient for the cell monolayer... 

The concurrent identification and quantification of organic impurities is a principal use of liquid chromatography in the pharmaceutical industry. However, the application of liquid chromatography to this task highlights a weakness of this technique when compared to gas chromatography specifically, the lack of a universal detector. Great strides have been made to create detectors and hyphenated techniques to address these problems. However, multiple detectors and analytical procedures may be necessary to accurately and specifically identify and quantify the impurities in complex systems. 

Though in competition with other analytical techniques, CE has proven its potential and necessity to be used for the characterization of small-molecule pharmaceuticals. Due to the versatility of the system, CE can be applied for the determination of physicochemical properties, identification, purity and stability analysis, and cleaning verification of the drug substance, its precursors, process chemicals, the drug product, and its excipients. 

The coupling of a mass spectrometer to CE and CEC provides a powerful system for the analysis of pharmaceuticals and complex biological mixtures. This can replace or complement other conventional detection methods such as UV, electrochemical, or LIE that provide less structural information. The use of mass spectrometer as a detector enhances the usefulness of the CE and CEC and allows an efficient separation and identification of complex mixtures, obtaining structure and/or molecular mass information. The choice of mass analyzers used in CE/CEC-MS depends on factors such as sensitivity, mass resolution, requirement for structural elucidation, and the type of application (Table 5). The analyzers that have been used in CEC analysis include time-of-flight (TOE), quadrupole (Q), ion-trap (IT), fourier... 

W.L. Yoon, N.C. North, R.D. Jee and A.C. Moffat, Apphcation of a polar qnahflcation system in the near infrared identification and qualification of raw pharmaceutical excipients. In Davies, A.M.C. and Giangiacomo, R. (eds). Near Infrared Spectroscopy, Proceedings of the International Conference, 9th, Verona, Italy, June 13-18, 1999, NIR Publications, Chichester, UK, pp. 547-550, 2000. 

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