Frequency domain photon migration consists of launching an intensitymodulated
near-infrared light into the powder medium and measuring the amplitude,
mean-intensity, and phase shift of detected intensity modulated light for extracting both
the isotropic scattering and absorption coefficients of the powder bed. The dependence
of absorption coefficient upon the active pharmaceutical ingredient (API) concentration
of powder blend enables FDPM to monitor blending homogeneity. The volume sampled
by FDPM in powder blend was investigated through a designed heterogeneity
experiments. A model which describes the visitation probability of a local region by
migrating photons was developed to theoretically determine the sampled volume of
FDPM in terms of signal-to-noise ratio. The applicability of FDPM in monitoring
blending homogeneity was directly verified by measuring the API contents in a series of
industrial samples, which were retrieved from various locations at various times in an
actual pharmaceutical blending process. The FDPM measurement results were
consistent with the traditional analysis using high performance liquid chromatography.
The homogeneity evolution revealed through FDPM agreed with the well-established
first order model of blending. A simulation method was developed which consisted of
(i) dynamic simulation for generating the powder structure; (ii) the completely-randommixture
model for predicting the spatial distribution of API particles within the powder
bed; and (iii) Monte Carlo simulation for tracking photon trajectories within the powder
bed. The simulation of photon migration in powder blend revealed that while both the
isotropic scattering and absorption coefficients increased with the solid-volume fraction,
the ratio of absorption coefficient to the isotropic scattering coefficient is (i) independent
of the solid-volume fraction; (ii) linearly dependent upon the API concentration; and (iii)
appropriate for monitoring the powder blending homogeneity under simultaneous
variations of solid-volume fraction and API content. Finally, a rigorous two-speed
diffusion equation for describing photon migration in powders was derived from the
two-group radiative transfer equations and the analytical expression of the isotropic
scattering coefficient was provided. The theoretical results agreed well with the
experimental measurements in resin powder media and resin suspensions.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/4433 |
| Date | 30 October 2006 |
| Creators | Pan, Tianshu |
| Contributors | Sevick-Muraca, Eva M. |
| Publisher | Texas A&M University |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | 1466990 bytes, electronic, application/pdf, born digital |
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