The Influence of Tablet Formulation, Drug Concentration, and pH Modification on the Stability of Extemporaneously Compounded Levothyroxine Suspensions.

Abstract

Three brands of levothyroxine tablets are currently available in New Zealand (Eltroxin, Mercury Pharma, Synthroid) for extemporaneous compounding into suspensions. This study aims to determine whether tablet brand (i.e., formulation), concentration, storage conditions, as well as pH, impact the stability of compounded levothyroxine suspensions. Using the three available brands of levothyroxine tablets, suspensions were compounded at concentrations of 15 µg/mL and 25 µg/mL and stored at 4°C and 22°C. Samples were withdrawn weekly for 4 weeks, and chemical stability was evaluated using high-performance liquid chromatographic analysis. Physical appearance, ease of resuspension, and pH were also monitored weekly. To evaluate the effect on drug stability, pH modifiers were added to a suspension. As demonstrated by high-performance liquid chromatographic analysis, the suspensions compounded from the Eltroxin and Mercury Pharma tablets were more stable (>90% remaining after 4 weeks) than Synthroid across both storage conditions and concentrations. The drug was more stable at the higher concentration of 25 µg/mL than at 15 µg/mL. Levothyroxine was stable when pH was increased to pH 8 through the addition of sodium citrate; stability was reduced at a lower pH. Storage temperature did not affect the stability of the suspensions during the 4-week study. This is the first study demonstrating the impact of tablet brand, with different excipients, and drug concentrations on stability, and thus the beyond-use date of the compounded levothyroxine liquid formulations. The pH control achieved by sodium citrate, either as an excipient in tablets or an additive during compounding, improved drug stability.