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

1. Acta Pharm. 2026 Jun 30;76(2):1-11. doi: 10.2478/acph-2026-0018. Print 2026 Jun 1. SEM/EDS analysis as a complementary tool for continuous improvement of cefixime granules for oral suspension. Mitrevska I(1)(2), Karpicarov D(1), Mihailovska A(3), Mirakovski D(3), Paneva O(2), Petrushevski G(4). Author information: (1)1Faculty of Medical Sciences, Goce Delcev University, 2000Stip, Republic of North Macedonia. (2)2Quality Assurance, ALKALOID AD Skopje, 1000Skopje, Republic of North Macedonia. (3)3Faculty of Natural and Technical Sciences Goce Delcev University, 2000Stip, Republic of North Macedonia. (4)4Quality Control Pharmaceuticals ALKALOID AD Skopje, 1000Skopje Republic of North Macedonia. 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. © 2026 Ivana Mitrevska et al., published by Croatian Pharmaceutical Society. DOI: 10.2478/acph-2026-0018 PMID: 42412954 [Indexed for MEDLINE]

{
  "language": "lang-en",
  "diagnosis": [
    "ra"
  ],
  "specialty": "rheumatology",
  "study_type": "cohort",
  "evidence_level": "level-3",
  "v6_autopublish": true,
  "clinical_impact": "moderate-impact",
  "practice_recommendation": "monitoring"
}