A system of dual-component powder mixtures, varying in excipient particle size and concentration of active pharmaceutical ingredient (API), is analyzed using frequency domain photon migration (FDPM) techniques. The results show that the FDPM-measured absorption coefficient increases linearly with increasing API concentration whereas the isotropic scattering coefficient shows no sensitivity to changes in API concentration. It is further seen that the absorption coefficient of blends, owing to the API, is not only linearly dependent on its concentration, but that this relationship is furthermore related to the excipient particle size. Finally, a comparison between near-infrared absorbance and FDPM-measured isotropic scattering as a function of reciprocal particle size is made to highlight FDPM as a powerful particle sizing tool without need for calibration. Overall, this study presents FDPM as a comprehensive method for detection of API concentration independent of excipient particle size. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association.

Near-infrared spectroscopy Light scattering Particle size Absorption spectroscopy Mixing

active pharmaceutical ingredient isotropic scattering coefficient measurement linear system particle size near infrared reflectance spectroscopy calibration sensitivity analysis unclassified drug mathematical analysis intermethod comparison concentration (parameters) Article drug mixture powder excipient frequency domain photon migration