Characterization of different laser irradiation methods for quantitative Raman tablet assessment.

Quantitative Raman spectroscopy of conventional wet granulated pharmaceutical immediate release tablets and subsequent data evaluation was investigated. Different aspects of quantitative assessment of active pharmaceutical ingredient (API) in intact tablets with special focus on sub-sampling issues were addressed. Four different geometric laser irradiance patterns were examined to study the effect of sub-sampling within the tablets. The Raman data was evaluated using both univariate and multivariate techniques. UV absorbance spectroscopy was used as a reference method. The best result in terms of prediction error was attained by irradiating a large area of the tablets. Using multivariate calibration with multiplicative signal correction (MSC) the prediction error was 1.7%. In addition, the effect of tablet density on the Raman assessment was investigated. It was found that quantitative Raman assessment of chemical content can be made insensitive to variations in tablet density corresponding to a manufacturing compression interval of 5-20 kN provided that adequate data treatment is used. A short discussion about sample heating in the context of different irradiation patterns is included with reference to previous work. In conclusion, the present study provides a platform for developing an implementation strategy for quantitative Raman spectroscopy for both laboratory analysis and process analytical technology (PAT) applications.