SEM/EDS analysis as a complementary tool for continuous improvement of cefixime granules for oral suspension

The aim of this study was to evaluate scanning electron
microscopy (SEM) combined with energy-dispersive
X-ray spectroscopy (EDS) as complementary analytical
tools for supporting continuous improvement in pharmaceutical granule manufacturing. Pilot-scale cefixime
granules for oral suspension were prepared as defined
process scenarios, including placebo, reference, intermediate, stress-exposed, and optimised batches. SEM
was used to compare granule morphology, surface
integrity, and agglomeration behaviour, whereas EDS
provided qualitative and semi-quantitative information on localised elemental composition, with emphasis on sulfur as an API-related marker and oxygen-to-
-sulfur trends as surface-sensitive indicators of
process- or stress-related variability. Intermediate and
stress-exposed batches showed increased surface
roughness, microstructural deterioration, and higher
oxygen-to-sulfur ratios, whereas reference and optimised batches showed more uniform morphology and
comparable elemental profiles. The findings indicate
that SEM/EDS can provide useful material-level insight
into process-related variability and may support root-
-cause investigation and process refinement. Overall,
SEM/EDS is proposed as a complementary, localised,
and semi-quantitative approach for supporting continuous improvement in pharmaceutical granule manufacturing.