Thermal Stability of Dexamethasone-Evaluation with Regard to Modern Medicinal and Pharmaceutical 3D-Printing Applications

Abstract

The high-temperature thermal stability of dexamethasone (DEX) was systematically investigated under nitrogen and air atmospheres using non-isothermal thermogravimetry at heating rates of 0.1-20 degrees C center dot min(-1). The thermal decomposition was found to initiate below the melting temperature, proceeding via a three-step pathway that generated a complex mixture of volatile and condensed by-products (similar to 10% solid residuum at 550 degrees C). Kinetic modeling was realized using the single-curve multivariate kinetic analysis (sc-MKA), and was based on the autocatalytic framework with temperature-dependent parameters, combined with consequent reaction mechanisms. An excellent agreement of the theoretical model with the experimental data enabled reliable predictive extrapolations to pharmaceutical processing conditions. Whereas the onset of degradation was observed at similar to 180-190 degrees C, significant decomposition rates (>1% mass loss during first 5 min) were only reached above 220 degrees C, well above the processing windows of most pharmaceutical polymers. Consequently, dexamethasone can be considered thermally stable for hot-melt extrusion and fused deposition modeling, except in high-temperature-processing applications involving polymers such as, e.g., polylactic acid, polyvinyl alcohol, or thermoplastic polyurethanes. Importantly, the study highlights that reliable kinetic predictions require measurements across a broad heating-rate range and in both oxidizing and inert atmospheres, with special emphasis on low heating rates (<= 0.2 degrees C center dot min(-1)), which proved critical for capturing early-stage degradation. These findings provide a rigorous kinetic framework for ensuring safe incorporation of DEX into advanced pharmaceutical and medical device formulations.