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

Abstract

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.