Evaluation of ingredient concentration in powders using two-speed photon migration theory and measurements

Two-speed photon migration in densely packed powder blends wherein the particle diameters are much larger than the incident wavelength are simulated with (i) dynamic simulation of particle sedimentation for generating powder structure, (ii) the complete-random-mixture model for predicting the active pharmaceutical ingredient (API) distribution within the powder bed, and (iii) Monte Carlo for tracking the photon trajectories. The simulation results reveal that while both absorption and isotropic scattering coefficients increase with solid-volume fraction ranging from 0.12 to 0.64, the absorption-to-isotropic-scattering ratio is (i) independent of the solid-volume fraction for particle refractive index ranging from 1.2 to 1.8 and (ii) linearly dependent upon the API volume concentration ranging from 0% to 5%. Frequency domain photon migration measurements of resin powder beds of varying particle size verified the developed simulation method. Measurements of lactose powder beds of varying particle size, solid-volume fraction, and ferric oxide particles content verified the simulation results that evidence independence of the absorption-to-isotropic-scattering ratio upon solid-volume fraction.