Pharmaceutical tablets and near-infrared spectral information : investigation of sampled tablet sections and press effect on predictions

Near-infrared (NIR) spectroscopy offers tremendous advantages for pharmaceutical
manufacturing as a fast and non-destructive method of quantitative and qualitative
analysis. Content uniformity (end-product analytics) and process analytics are two
important applications of the method.
Both modes of analysis, diffuse transmission (DT) and diffuse reflection (DR) are
sensitive to changes in sample physical parameters. Scaling as well as baseline shifts due
to tableting variations would be a potential cause of many outliers and prediction errors,
and therefore these effects need to be more clearly understood. Moreover, there is
currently no clear literature information about the sampling span in both modes
(horizontal or radial in DT, and vertical or information depth in DR). This information is
vital in content prediction using NIR in cases where inhomogeneities in the sample are
detrimental (e.g. low-dose API in large samples).
The press effect was investigated using placebo tablets of different thickness and
porosity ranges, which showed an exponential relationship with the diffuse
transmission (DT) signal. The drug content of 2.5% m/m folic acid tablets produced
under different compaction conditions was predicted and found to be in statistical
agreement with UV assay results after inclusion of physical outliers to the training sets.
To determine the sampling span in DT, placebo tablets of 10 mm diameter were covered
by different paper filters with incremental central block and the DT maximum at 8880
cm-1 was used to assess the degree of block. 90% of the signal was detected from a
diameter of up to 7 mm.
For DR information depth assessment, three experiment approaches were pursued: I.
0.5–10 mm incremental thickness placebo tablets with constant porosity, II.
MCC/Phenylbutazone (PBZ) double layered (DL) tablets (PBZ layer 0-100% in 0.5 mm
steps) and III. Comparison of placebo and 30% caffeine tablet cores with incremental
film coating (film thickness of 0 – 0.35 mm). Incremental thickness and cluster analysis
of DL tablets showed that DR information depth was < 0.5 mm, while the data fitting
from incremental coating showed that signal drop reached 50% at 0.05 – 0.07 mm
depending on the wavenumber and 90% signal drop (10% information content) can be
seen between 0.2 – 0.25 mm without extrapolation.