Assessment of epinephrine sublingual stability and permeability pathways to enhance its permeability for the treatment of anaphylaxis

• Published in: European journal of pharmaceutical sciences 2021-12, Vol.167, p.106025-106025, Article 106025
• Main Authors: Rawas-Qalaji, Mutasem, Bafail, Rawan, Cagliani, Roberta, Haider, Mohamed, Hussain, Zahid
• Format: Article
• Language: English
• Subjects: Anaphylaxis; Epinephrine; Fast disintegrating tablets; Permeability; Stability; Sublingual
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2021.106025

[Display omitted] Prompt epinephrine (Epi) injection using auto-injectors is the initial life-saving out-of-hospital treatment for anaphylaxis. However, patients and healthcare providers are eagerly awaiting a more convenient alternative dosage form that would overcome auto-injectors drawbacks. Previously, we extensively evaluated multiple alternative fast-disintegrating sublingual Epi tablet (FDSTs) formulations. However, the sublingual stability of Epi and effect of modifying the sublingual microenvironment pH on its stability and transport pathways were not yet fully investigated. Results depicted that Epi remained sufficiently stable at various pHs in human saliva and porcine sublingual tissue's extract. Epi permeability (EP) through excised porcine sublingual membrane was greatest at pH 8.0 (p 5 min). Meanwhile, Na Carb and SDS combination increased EP 23-fold without a delay. It is evident that pH-modifiers or their SDS combination showed promising potential to enhance Epi sublingual permeability and further reduce the required Epi dose using FDSTs as a feasible alternative to Epi auto-injectors.