Clarification of the internal structure and factors of poor dissolution of substandard roxithromycin tablets by near-infrared chemical imaging.

ABSTRACT

The spread of substandard and falsified medicines has become a global problem, especially in low- and middle-income countries (LMICs). Previously, we found that some tablets containing the same active ingredient had large differences in their dissolution even though their contents were comparable. In this study, we investigated the poor dissolution of roxithromycin tablets using near-infrared chemical imaging (NIR-CI) to visualize the internal tablet structure. Roxithromycin tablets collected in LMICs and the pioneer product Rulid® as a reference were cut to a flat surface for analysis. NIR spectral data were normalized, and a principal component analysis was performed to create a tablet internal structure image. For Rulid®, the differences between the spectra with high and low scores were small, and well-defined aggregation of ingredients was not observed. However, large differences in the scores were found for roxithromycin tablets manufactured in some LMICs, and non-uniformity of ingredient distribution and aggregation were observed. Additionally, some pharmaceutical excipients, such as starch or magnesium stearate, were found in certain aggregates by comparing NIR spectra. The NIR-CI results showed some excipients existed as large aggregates, which indicated that the ingredients were not evenly mixed in the roxithromycin tablet, and this contributed to its poor dissolution.