Impact of excipient particle size on measurement of active pharmaceutical ingredient absorbance in mixtures using frequency domain photon migration.

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. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1879-1889, 2004