Infrared imaging of laser-induced heating during Raman spectroscopy of pharmaceutical solids

Raman spectroscopy is finding increasing popularity as an analytical technique for the analysis of pharmaceutical powders and solid dosage forms. It is well known that illumination by the high intensity lasers used in Raman spectrometers can result in sample heating, however, the extent of the problem has not been assessed for pharmaceutically relevant materials. Using direct thermal imaging of compressed powders, the extent of heating for microcrystalline cellulose (MCC), vanillin, ibuprofen and stearic acid was measured as a function of laser intensity. MCC was found to be the most susceptible to sample heating while ibuprofen was least sensitive. At high laser powers (1.5 W), samples were heated by between 38 and 60 degreesC while at more moderate laser powers (0.7 W) the degree of heating was between 20 and 30 degreesC. The kinetics of the heating process were mathematically modeled for MCC and the derived constants were used to predict the rotation speed necessary to prevent a solid state transition in a heat sensitive compound, theophylline monohydrate. Experimental measurements at different rotation speeds verified that the estimated rotation speed reduced sample heating by the desired amount. In conclusion, the extent of heating is clearly of some concern for pharmaceutical materials but can be substantially reduced by sample rotation. (C) 2002 Elsevier Science B.V. All rights reserved.