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It is customary to rotate samples in Raman spectroscopy to avoid absorption or sample heating. In FT-Raman experiments the rotation is always shown (typically 30-60 rpm) because higher speeds are thought to generate noise in the spectra. In this article we show that more rapid rotation is possible. A tablet containing maleic acid and one made up of sub-millimetre silica particles with metoprolol succinate as active ingredient were rotated at different speeds, up to 6760 rpm. The FT-Raman spectra were recorded and studied. We conclude that it is perfectly acceptable to rotate samples up to 1500 rpm.

The reliability with which an external reference sample can be used to standardise the intensities of Raman scattering spectra is assessed. By comparing the ratios of single band intensities of Raman scatter in a two component liquid mixture with those between the mixture and an external standard it is shown that the latter is more than adequate for most quantitative Raman analysis. Coefficients of variance in repeated experiments on the same sample are approximately 1%, when comparing single band heights on spectra recorded with modest laser powers over 2 min. When using the whole spectrum, these coefficients are significantly lower.

We analyzed binary mixtures of polymorphs A and B of chlorpropamide ((1-[4-chlorobenzenesulphonyl]-3-propyl urea)) by near-infrared Fourier transform Raman spectroscopy (FTRS). The individual polymorphs were prepared and characterized by differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) microscopy, and physical appearance. The FTR spectra of the two polymorphs showed distinct differences which result from "crystal splitting" effects. A series of 13 different mixtures of polymorph A and B was prepared by geometric mixing and their FTR spectra statistically analysed by factor analysis programming. Predictions of the A/B polymorphic composition of mixtures were made and compared with the theoretical values. The results demonstrate that FTRS combined with factor analysis programming may be successfully applied to the in situ monitoring of the A/B polymorphic nature of a chlorpropamide sample.

FT-Raman spectroscopy (FTRS) has been used to characterize microspheres produced from the pharmaceutical polymer Eudragit RS containing a range of concentrations of the drug sulfasalazine. While pure sulfasalazine produced an intense and complex Raman spectrum, the spectrum of drug-free Eudragit RS microspheres was considerably weaker in intensity and contained only a few prominent Raman scattering peaks. In spectra of the drug-polymer microspheres, peaks arising from the individual components could be identified. This enabled a quantitative analysis to be undertaken by calculating the ratio between the area of a sulfasalazine peak and the area of a Eudragit RS peak for each microsphere spectrum. A correlation was shown between the peak area ratio and the microsphere sulfasalazine content. FTRS was then applied to a series of microsphere samples which had been dissoluted into pH 7 buffer for 1, 3, 6, 9, 12, or 24 hr. For each spectrum, the drug-polymer peak area ratio was determined and this in turn enabled calculation of the residual drug content of the microsphere sample. FTRS-calculated data showed good agreement with microsphere drug content values determined spectrophotometrically.

Near infrared Fourier-transform (FT) Raman spectroscopy is shown to be a useful spectroscopic tool for the molecular structural analysis of drugs and biomedical polymers. The technique has been applied to the non-invasive investigation of the hydrolytic degradation of a biodegradable polymer in water over a period of 15 days and to the analysis of a drug within a polymer vehicle over a wide drug concentration range. This work demonstrates the potential value of FT Raman spectroscopy in the field of pharmaceutical science.