Mass median particle size determination of an active compound in a binary mixture using near-infrared spectroscopy

Near-infrared (NIR) spectroscopy was applied to the determination of the mass median particle size (mmps) of a micronised active compound contained within a lactose monohydrate matrix. The concentration of the active compound was 4% by weight, and covered a mmps range between 8 and 20 µm. Multivariate statistical analysis was applied to zero order NIR spectra, using particle size data obtained by laser diffractometry as the reference technique. Based upon a limited data set and partial method validation, principal component regression using three factors produced a standard error of calibration in the order of 2 µm. Due to the speed, simplicity and low operating costs of this technique, it has been demonstrated that NIR spectroscopy is a viable alternative to methods that have been applied to this particular problem.