Purpose: The study was performed to assess the short-term stability of epinephrine (Epi) at wide range of pH. Modification of the pH of the absorption’s microenvironment can alter the degree of drug ionization and therefore its permeability. Altering the saliva pH (5.5-7.2) in order to enhance Epi sublingual abortion and reduce its absorption variability can, on the other hand, negatively affect its stability. We hypothesized that altering Epi ionization by modifying the pH of absorption medium without negatively affecting Epi stability can enhance Epi permeability and optimize sublingual Epi delivery as an alternative route for the treatment for anaphylaxis.
Methods: Epi Bitartrate (EpiBit) equivalent to 20 mg Epi was dissolved in 2 mL of Mcvilian buffer (n=3) prepared at pH 1.2, 3.5, 4.5, 5, 5.5, 6, 6.8, 7.4, and 8. Aliquot samples were withdrawn at 2 min (maximum time for sublingual administration), 4 min, 6 min, 10 min, 15 min, and 30 min. Withdrawn samples were immediately diluted with a stabilizing solution containing 0.1 M perchloric acid and 0.1 mM sodium metabisulfite to stop any further Epi degradation. Collected samples were transferred into HPLC vials for HPLC analysis using a UV detector. Epi recovery % at T0 was used as a positive control for each sample. The mean±SD of Epi recovery (%) for each pH were statistically compared using Repeated Measures-ANOVA and Tukey-Kramer Tests.
Results: Mean±SD Epi recovery (%) was not significantly different (p>0.05) from the positive control (T0) at the different sampling time intervals in pH that ranged from 1.2 to 3.5 and 5.5 to 8 (Figure 1). At pH 4, 4.5 and 5, Epi recovery (%) declined significantly (p<0.05).
Conclusion: Epi was relatively stable for the time-period required for its sublingual administration at the saliva pH and up to pH 8. Alerting the pH of the absorption’s microenvironment up to pH 8 to enhance Epi sublingual delivery and reduce its absorption variability should not affect its stability.
Rawan Bafail– Nova Southeastern University, Florida