Alcohol-free Extemporaneous Formulations of Furosemide Are Chemically and Physically Stable in Ora-Blend Products for 30 Days

Abstract

Commercially available oral liquid formulations of furosemide contain ethanol. However, ethanol can lead to toxicity, particularly in neonates and young children. This study's objective was the development of ethanol-free furosemide suspensions and to determine whether suspending vehicles, temperature, and pH have an impact on the physical and chemical stability over a 30-day period. Formulations containing 2 mg/mL furosemide were prepared by crushing furosemide tablets and mixing with commercial vehicles Ora-Blend, Ora-Blend SF, or SyrSpend-SF Alka. As the stability of furosemide is reported to be pH-dependent, Ora-Blend and Ora-Blend SF were used both with and without pH adjustment. The resulting suspensions were stored at either 4oC or 25oC over 30 days with physical and chemical stability monitored. Negligible changes were noted in appearance over 30 days. The pH of all formulations remained relatively consistent throughout the study period. All formulations were chemically stable, as determined by high-performance liquid chromatography, retaining >90% of initial concentration over 30 days at 4oC and 25oC. Interestingly, suspensions remained chemically stable regardless of the pH of the vehicle, with the pH of the formulations ranging from 4.2 to 7.7. A simple extemporaneous compounding method was used to prepare alcohol-free furosemide suspensions that were stable for 30 days at 4oC and 25oC. These findings are important for patients who cannot tolerate, or wish to avoid, alcohol, including the pediatric population.