Reliable and non‐destructive Raman analysis to determine the urea concentration in a cream formulation

We present a reliable and nondestructive analytical method for the determination of urea concentration in a pharmaceutical cream formulation using Raman spectroscopy. A pharmaceutical cream is a highly viscous emulsion; therefore, its composition and physical mixing could be inhomogeneous on a microscopic scale. The local environment around the urea could vary, which could influence the molecular vibrations of the urea molecule. As expected, when Raman spectra were collected by focusing the laser onto a tiny area (∼2–3 µm), the position of the urea band at 1003 cm−1 varied as a result of the microscopic inhomogeneity within the sample. Therefore, acquisition of Raman spectra representative of the entire sample rather than a localized portion of it is very important for the analysis of pharmaceutical creams. Based on the preliminary Raman mapping results of a urea cream, a sample area of at least 750 × 750 µm should be covered for reliable quantitative analysis. In this study, we used a wide-area illumination scheme capable of covering a sample area of 28.3 mm2 for Raman spectral collection in order to ensure a reliable representative sample. In addition, to simplify the measurements, Raman spectra of urea creams in plastic bottles were directly collected without further sampling, and partial least squares regression was used for quantitative analysis. The urea concentrations were accurately determined despite the spectral collection being performed through plastic bottles. Copyright © 2010 John Wiley & Sons, Ltd.