Purpose: The study was performed to evaluate the effect of modifying the pH on the sublingual permeability of epinephrine (Epi) in order to alter its degree of ionization. We hypothesized that altering Epi ionization by modifying the pH of absorption medium 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 (phosphate acetate buffer) (n=4) prepared at different pH including pH 5, 6, 6.8, 7.4, and 8 as a diffusion medium. The permeation of Epi was evaluated through an excised porcine sublingual membrane using static vertical Franz diffusion cells at controlled temperature of 37oC. EpiBit solution was placed in the donner chamber and phosphate buffer at pH 7.4 (pH of the blood) was used in the receiver chamber. Aliquots, 200 μL, were withdrawn from the receiver chamber at several time intervals. The volumes withdrawn were replenished with fresh phosphate buffer and the collected samples were filtered and transferred into HPLC vials for HPLC analysis using a UV detector. The cumulative amount of the drug permeated over time (AUC0-90min), influx (J), and permeability coefficient (P) were calculated and statistically compared using ANOVA and Tukey-Kramer Tests.
Results: pH had a significant effect on Epi sublingual permeability. As the pH was increased, the degree of ionization was decreased and result in increasing the sublingual permeation of Epi. The mean (± SD) AUC0-90min of permeated Epi resulted in a linear increase (R2=0.8) due to the increase in the medium pH (Figure 1). Mean (± SD) AUC0-90min, J, and P at the various pH tested were significantly (p<0.05) different from each other and significantly increased as the pH was increased except between EpiBit solutions tested at pH 5 and pH 6 (Table I).
Conclusion: Increasing the pH of the diffusion medium and the subsequent reduction in Epi ionization can result in a significant increase in the Epi sublingual permeation.
Rawan Bafail– Nova Southeastern University, Florida