Thermal stability of mafenide and amphotericin B topical solution

Objective: Fungal infections remain a major cause of mortality in the burned population. Mafenide acetate/amphotericin B solution (SMAT) has been used topically for prophylaxis and treatment of these infections. Current manufacturer guidelines only guarantee the stability of mafenide solution and amphotericin B at room temperature. Additionally, the recommended maximum storage time for mafenide solution is 48 h, leading to significant financial and material loss when unused solutions are discarded. The purpose of this study was to characterize the chemical stability, structure and bioactivity of SMAT stored at 2 °C, 25 °C, and 40 °C for up to 90 days. Methods: Stability analyses of SMAT solutions containing 2.5% or 5% mafenide plus 2 μg/mL amphotericin B were performed using high performance liquid chromatography. Chemical structure was assessed using Fourier-transform infrared spectroscopy. Bioactivity against clinically relevant species was examined. Results: The chemical structure and stability of mafenide did not change over 90 days at all temperatures. Amphotericin B was undetectable in SMAT solutions after two days at high temperatures, which was slowed by refrigerated storage. Against Staphylococcus aureus, SMAT activity began to decrease generally between two and seven days. Against Pseudomonas aeruginosa, activity slowly tapered and was gone by day 90. SMAT retained high bioactivity against Candida albicans for over 40 days and was not affected by temperature. Conclusions: The amphotericin B component of SMAT is degraded within 2 days under warm storage. While mafenide was stable over 90 days, the bioactivity of SMAT solution may be lost within 2 days as well.