Comparative particle size determination of phenacetin bulk powder by using Kubelka–Munk theory and principal component regression analysis based on near-infrared spectroscopy

Purpose: The purpose of this study is to investigate the effect of particle size on Kubelka–Munk theoretical light diffusion of NIR spectra. And a chemoinfometrical method for quantitative determination of particle size of phenacetin crystalline powder based on Fourier-transformed near-infrared (FT-NIR) spectroscopy was established. Method: The sample powders of phenacetin were obtained by sieving using 37–590 μm screens. NIR spectra were taken with a total 60 NIR data points by using a FT-NIR spectrometer. Results: The NIR absorption patterns were almost identical for the samples. However, the base line of the spectrum was observed to increase with decreasing sample powder particle size. The scatter coefficient constants (S) were calculated from NIR spectra based on Kubelka and Munk light scattering theory. The S values determined were found to be constant within the wavenumbers studied; i.e., 4000–10 000 cm−1. However, this light scatter coefficient, S, for phenacetin particle was found to be inversely proportional to particle size. Subsequently, the principal component regression (PCR) analysis based on a three-principal component model was applied in the analyses of NIR spectra of phenacetin powder samples with various particle sizes. By applying this method, the particle size for phenacetin can be estimated form the light scatter coefficient, S. The resulting plot showed a linear relationship between the predicted and actual particle size with a slope of 0.9167, an intercept of 20.61, and a correlation coefficient of 0.9147. The loading vector of PC1 showed a plateau at 4500–10 000 cm−1, and the score of PC1 increased with increase of particle size. Conclusion: Quantitative particle size evaluation of phenacetin crystalline powder using the PCR method based on NIR spectra was useful for practical purpose in pharmaceutical industry, and their background was clarified by using Kubelka–Munk scattering theory.