Investigation of the effect of particle size on Transmission Raman spectral features of powder samples and its influence on the quantitative analysis

Abstract

Transmission Raman spectral features of solid samples with different particle sizes were characterized and investigated subsequent trends of particle size-induced intensity variations. For the investigation, transmission Raman spectra of lactose powders with four different particle sizes were acquired. The lactose peak intensity increased with the elevation of particle size. Based on Monte Carlo simulation, when the particle size became larger, the mean free path becomes longer from the decreased scattering coefficient. So, the laser photons travel farther into the lactose packing and the transmitted Raman signal accordingly increased as observed experimentally. Next, the photon propagation in binary-component samples (powders of ambroxol/lactose), in which the particle size of the lactose was solely changed, were examined. Similar to the result obtained from single-component lactose powders. The intensity of the ambroxol peak elevated with increasing size of surrounding lactose particles, although the particle size of the ambroxol was unchanged. The larger lactose particles made the laser radiation more broadly interacted with ambroxol and the generated ambroxol photons travelled farther, thereby leading to the increase in the peak intensity. The accuracies for the determination of ambroxol concentrations by partial least squares (PLS) became substantially degraded with when the size of lactose particle was largest. Since the ambroxol photons were more laterally distributed in the sample composed of the largest lactose particle, the probabilities of photons reaching the detector became more variable and the degradation of reproducibility inducing the deterioration of accuracy was subsequently consequential. In final, transmission spectral features of the tested samples were also particle-size dependent and the particle size of a sample was the must-consider issue when accurate determination of component concentration intended.