Frequency-domain photon migration measurements for quantitative assessment of powder absorbance: A novel sensor of blend homogeneity.

The measurement and analysis of frequency-domain photon migration (FDPM) measurements of powder absorbance in pharmaceutical powders is described in the context of other optical techniques. FDPM consists of launching intensity-modulated light into a powder and detecting the phase delay and amplitude modulation of the re-emitted light as a function of the modulation frequency. From analysis of the data using the diffusion approximation to the radiative transport equation, the absorption coefficient can be obtained. Absorption coefficient measurements of riboflavin in lactose mixtures are presented at concentrations of 0.1 to 1% (w/w) at near-infrared wavelengths where solution absorption cross sections are difficult to accurately measure using traditional transmission measurements in nonscattering solutions. FDPM measurements in powders enabled determinations of absorption coefficients that increase linearly with concentration (w/w) according to Beer-Lambert relationship. The extension of FDPM for monitoring absorbance of low-dose and ultralow-dose powder blending operations is presented.