Rapid screening of physicochemical compatibility between co-administered injectable drugs using thermal and...

The concomitant administration of injectable drugs in hospital settings frequently involves extemporaneous combinations within the same infusion line, often without compatibility evaluation. This practice may compromise drug stability and patient safety, particularly in intensive care units characterized by complex polypharmacy regimens. In this study, a rapid screening protocol based on complementary thermal, spectroscopic, and morphological techniques was applied to investigate potential physicochemical interactions between injectable drugs under accelerated stress conditions. Dopamine, ondansetron, rocuronium, and fluconazole were combined pairwise as binary physical mixtures and subjected to controlled thermal and photonic stress. Differential scanning calorimetry, thermogravimetric analysis, FTIR spectroscopy, and stereomicroscopy were employed to detect early physicochemical interactions and stress-induced instability. Thermal analysis revealed melting point shifts, enthalpy reduction, amorphization, and premature degradation events for several combinations, indicating different levels of intermolecular interaction. FTIR and morphological analyses demonstrated that some changes in thermal profile were accompanied by chemically relevant alterations and progressive discoloration, particularly after combined thermal and light exposure. Dopamine/fluconazole and dopamine/ondansetron mixtures showed evidence of moderate solid-state interaction, while ondansetron/fluconazole exhibited increased susceptibility to stress-induced instability. Mixtures containing rocuronium exhibited greater sensitivity to combined thermal and photonic stress, especially ondansetron/rocuronium, which showed marked light-dependent instability. Overall, the proposed approach proved useful as a rapid preliminary risk-ranking strategy to identify injectable drug combinations requiring further compatibility investigation under clinically relevant conditions.