Application of Monte Carlo simulation-based photon migration for enhanced understanding of near-infrared (NIR) diffuse reflectance. Part I: Depth of penetration in pharmaceutical materials.

This is the first of a series of articles applying Monte Carlo simulation-based photon migration to enhance understanding of near-infrared (NIR) diffuse reflectance in pharmaceutical analysis. This article aims to enhance mechanistic understanding on the interaction between NIR light and pharmaceutical materials, specifically focusing on the physical effects on NIR absorbance and depth of penetration profiles. Variations of particle size of lactose powder and density of a model tablet were used here as examples to represent the physical effects. An NIR chemical imaging system was used to measure the light-interrogated area and the depth of penetration. Absorption and reduced scattering coefficients of powder and tablet samples, determined by spatially resolved spectroscopy, were combined with Monte Carlo simulation-based photon migration to illustrate the mechanism of NIR light interaction with pharmaceutical materials. The empirically measured data and simulated results were consistent with one another and demonstrated a relationship between the physical effects of pharmaceutical samples and NIR absorbance/depth of penetration. The absorption coefficients and reduced scattering coefficients were discovered to be the dominant factors in the NIR absorbance profile and depth of penetration characteristics, respectively. The enhanced understanding of the roles of absorption and scattering in NIR diffuse reflectance is expected to provide useful insights for efficient multivariate calibration, unique spectroscopic pretreatments, and depth-resolved NIR chemical imaging.