Impact of hydration state and molecular oxygen on the chemical stability of levothyroxine sodium

Abstract

Levothyroxine sodium is an important medication used primarily for treating patients with hypothyroidism. Levothyroxine sodium tablets have been recalled many times since their 1955 introduction to the US market. These recalls resulted from the failure of lots to meet their content uniformity and potency specifications. The purpose of this study is to test the hypothesis that the chemical stability of levothyroxine sodium pentahydrate is compromised upon exposing the dehydrated substance to molecular oxygen. The impact of temperature, oxygen and humidity storage conditions on the stability of solid-state levothyroxine sodium was examined. After exposure to these storage conditions for selected periods of time, high performance liquid chromatography (HPLC) was used to quantify the formation of impurities. The results showed that levothyroxine sodium samples degraded significantly over a 32-day test period when subjected to dry conditions in the presence of molecular oxygen. However, dehydrated samples remained stable when oxygen was removed from the storage chamber. Furthermore, hydrated samples were stable in the presence of oxygen and in the absence of oxygen. These results reveal conditions that will degrade levothyroxine sodium pentahydrate and elucidate measures that can be taken to stabilize the drug substance.

• Degradation
• HPLC
• impurities
• levothyroxine sodium pentahydrate
• moisture
• molecular oxygen
• product quality
• solid state

Acknowledgements

The authors gratefully acknowledge the support of NIH INBRE program P20 RR016467 and would also like to thank recent graduates, Ryen Birkinbine and Eric Tsuji, for their help with various aspects of this project during their undergraduate studies at UH Hilo.

Declaration of interest

The authors report no declarations of interest.