Purpose: The purpose of the study was to evaluate the effect of different permeability enhancers on the sublingual permeability of epinephrine (Epi). We hypothesized that the incorporation of a permeability enhancer can further enhance Epi sublingual permeability as a potential alternative route of administration for the treatment of anaphylaxis.
Methods: Epi bitartrate (EpiBit) solutions (n=4) equivalent to 20 mg Epi containing 1% of API sodium dodecyl sulfate (SDS) or 16% of API palmitoyl carnitine chloride (PCC), as permeability enhancers, were dissolved in 2 mL of phosphate buffer at pH 6.8 (average saliva pH). Epi permeability with no penetration enhancers was used as a control. 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 Aliquots, 200 μL, were withdrawn from the receiver chamber at several time intervals. The volumes withdrawn were replenished with fresh phosphate buffer and the collected samples were filtered and transferred into HPLC vials for HPLC analysis using a UV detector.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: Mean (± SD) AUC0-90min, J, and P of permeated Epi with 1% SDS and 16% PCC were statistically higher (p<0.05) than the control. The AUC0-90min, J, and P of permeated Epi with SDS enhancer were significantly higher (p<0.05) than with PCC enhancer (Table I). Adding SDS 1% achieved the highest enhancement in Epi sublingual permeability and increased Epi permeability 10-fold compared to control.
Conclusion: Penetration enhancers were able to enhance the sublingual permeability of Epi. SDS was superior to PCC in enhancing the sublingual permeation of Epi. The incorporation of a permeability enhancer into Epi formulation can significantly enhance the permeability and potentially the sublingual absorption of Epi as a potential alternative route of administration for the treatment of anaphylaxis.
Rawan Bafail– Nova Southeastern University, Florida