(437c) A Novel Method for the Quantitative Mapping of the Density Profile of Roller Compacted Ribbons Via near-Infrared Reflectance Spectroscopy

Roller compaction is a common unit operation in
pharmaceutical processing of solid dosage formulations.  Ribbon density is a
key property to evaluate the consolidation state of the ribbons from different
roller compactors and at different scales.  Geometric density measurements are
challenging and inaccurate for textured surface ribbons typically used in
pharmaceutical applications.  Mechanical ribbon characterization techniques,
such as three-point bend strength and indentation hardness, can be highly variable
and sample destructive under certain circumstances.  Mercury porosimetry, while
accurate is sample destructive and time intensive.  Near-infrared (near-IR)
reflectance spectroscopy was used within suitable accuracy to quantitatively
map the density profile of roller compacted ribbons in a rapid, non-destructive
manner. 

This novel method included the use of a surrogate slug
calibration set for the ribbons and a small spot size for the near-IR
instrument to characterize the density across the width and length of the
ribbons.  The near-IR method's predicted density was compared to mercury porosimetry,
a ?gold standard? to characterize ribbon density.  The NIR method's predicted
density was determined via a partial least squares (PLS1) model and the spectral
best-fit method in literature for tablet hardness and ribbons [Journal of
Pharmaceutical and Biomedical Analysis 19, 351-362 and Journal of
Pharmaceutical Sciences 93(4), 1047-1053].  Ribbon samples characterized by NIR
and mercury porosimetry were analyzed as part of a Design of Experiments (DOE)
on roller compaction. 

During development of the NIR method, four factors were
hypothesized to contribute to the NIR method accuracy and precision in
reference to the mercury porosimetry method: regression method selection and
performance, slug vs. ribbon surface characteristics,  linearity of density
with compression force and analytical signal, and density homogeneity across
the ribbon fragment.  An investigation of each factor showed the regression
method and performance to be the most significant factor. 

The predicted density of ribbons from NIR was similar to,
but slightly offset from, the density measured by mercury porosimetry.  The
effects of roll pressure and roll gap on ribbon density measured using NIR
(spectral best-fit method) were comparable to the effects on ribbon density
determined using mercury porosimetry.  This indicates that NIR can be used to
evaluate relative density differences between scale or to understand effects of
processing factors.  Further refinement of the NIR method may allow absolute
determination of density.