Chemical & Pharmaceutical Research
Open AccessThermal-Cycling Stability of Cefixime Granules for Oral Suspension: Experimental Evaluation and FMEA-Based Risk Analysis for Pharmaceutical Distribution
Authors: Ivana Mitrevska, Dusica Angelovska, Olivera Paneva.
Abstract
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 thermal cycling 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 transport related 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.
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