The laser excitation wavelength is an important parameter in obtaining definitive Raman spectra from pharmaceutical drug substances. This paper investigates the effect of changing wavelength on the Raman spectra of four different drug substances: paracetamol, paroxetine and ranitidine (polymorphic forms I and II). Excitation wavelengths in the range 244 nm to 785 nm have been used. The fluorescence intensities in the Raman spectra were found to be negligible at the two extreme laser wavelengths but tended to interfere in the visible range. Resonance Raman enhancement was observed with 244 nm excitation but there was evidence for sample degradation. Furthermore, the site selective nature of the resonance enhancement reduced the differences between the Raman spectra of the two ranitidine polymorphs.

Raman spectroscopy is an integral tool for the identification, qualitative characterization, and quantitative analysis of drugs at the drug substance and/or drug product level. Significant advances in Raman spectrometer hardware, software control and data processing techniques have lead to unique applications of the Raman spectroscopic technique within the pharmaceutical industry. This Chapter presents applications of Raman spectroscopy as applied to the analysis of pharmaceutical drug substances as well as drug products. At the drug substance level, applications include the chemical and physical characterization of the API, microanalysis, contaminant analysis, and surface characterization. An extensive discussion is also presented on quantitative pharmaceutical analysis by Raman spectroscopy at the drug substance and drug product level including univariate versus multivariate analysis and method validation.

A modification to a conventional imaging Raman microscope to allow the acquisition of quasi-confocal spectra from multiple discrete Raman sampling volumes is reported. Preliminary performance was demonstrated by generating an extended area hyper-spectral chemical map of a number of ground sulfur crystals deposited on an aluminium mirror. Images generated using this multiplexed sampling arrangement were found to contain a number of weak ghost images (cross-talk), corresponding to inadequate separation of the focused laser spots at the sample.

The development of novel pharmaceuticals is driven by the requirement for high efficacy while retaining reduced side effects. This means that new medicines are very often relatively low dose (below 10% w/w drug substance in a tablet) and therefore they pose significant analytical challenges. Typical requirements include chemical identification of the drug substance, its crystalline form, the presence of any degradants and the distribution of drug substance and excipients.Raman spectroscopy is becoming one of the favoured techniques for looking at tablets. Raman is a non-invasive and non-destructive technique that is very important in the pharmaceutical industry. In addition, with a Raman microscope it is possible to obtain spectra from particles of micrometer dimensions. This means that limits of detection can be lower for inhomogeneous samples than those of non-microscopic Raman techniques.