Thermal-Cycling Stability of Cefixime Granules for Oral Suspension: Experimental Evaluation and FMEA-Based Risk Analysis for Pharmaceutical Distribution

Transportation of pharmaceutical products frequently exposes them to environmental stress, particularly
temperature excursions that may compromise stability. The aim of this study was to evaluate the impact of thermalcycling conditions on the stability of Cefixime granules for oral suspension, used here as a model product requiring
robust distribution stability. A thermal-cycling study was conducted in accordance with ICH and WHO stability
guidelines. A single pilot batch of the finished product was subjected to three consecutive cycles of −20 °C, +5
°C, and +30 °C, representing cumulative stress over approximately one month. Critical quality attributes including
physical appearance, pH, viscosity, dispersibility, dissolution, assay, related substances, and microbiological
quality were evaluated after each cycle. In parallel, a Failure Modes and Effects Analysis (FMEA) was performed
to assess transport-related risks and identify control strategies. All tested parameters remained within acceptance
limits throughout the study. Physical characteristics (appearance, odor, pH, viscosity, and dispersibility) were
unchanged. Assay values for both Cefixime and the preservative sodium benzoate were consistent across
conditions. Dissolution exceeded 80% within 15 minutes in all samples. Related and degradation products did not
surpass specified thresholds, and microbiological quality complied with pharmacopoeia requirements. The FMEA
identified customs delays, prolonged high-temperature exposure, and freezing risk as the most critical transportrelated hazards. Residual risk was substantially reduced by validated packaging, dual temperature monitoring,
and defined time-out-of-storage limits. The study demonstrated that Cefixime granules for oral suspension retain
stability under thermal-cycling conditions simulating transport. Combined with FMEA, the findings confirm that
the product can tolerate excursions between −20 °C and +30 °C for up to one month, ensuring suitability for
international distribution. Importantly, as this investigation was based on a pilot batch, confirmation with multiple
production batches is recommended for broader regulatory acceptance. The integrated approach highlights the
importance of combining experimental stability data with structured risk analysis to support robust pharmaceutical
supply chains.